Term
| Cystic fibrosis is the result of what deficiency? |
|
Definition
| Cl- transporter at plasma memebrane |
|
|
Term
| What is the primary mutation resulting in cystic fibrosis? |
|
Definition
|
|
Term
| Why does the mutant CFTR result in the cystic fibrosis phenotype? |
|
Definition
| Fails to fold correctly in ER and is shuttled for degradation |
|
|
Term
| N-linked glycosylation refers to… |
|
Definition
| …the addition of a saccharide group to an Asparagine (N) |
|
|
Term
| Describe the N-linked glycosylation that occurs in the ER. |
|
Definition
| Transfer of an oligosaccharide chain of 2 N-acetylglucosamine, 8-9 mannose, 3 glucose residues from dolichol pyrophosphate |
|
|
Term
| The ER's 'quality control' function may export a protein in a vesicle or allow it to undergo retrotranslocation. What's the difference? |
|
Definition
| Vesicular export is forward progression, retrotranslocation transfers defective protein to cytosol for ubiquitination and degradation. |
|
|
Term
| What causes the UPR in ER? |
|
Definition
| High levels of unfolded protein (stress) in the ER triggers BiP's release from its signaling molecule, triggering the Unfolded Protein Response. |
|
|
Term
| True or False. The motif information for exit signaling of ER transmembrane proteins are on the lumenal side. |
|
Definition
| False. The motif information is on the cytosolic side. |
|
|
Term
| Sphingomyelin and glycolipids are both derived from what? |
|
Definition
|
|
Term
| What is the primary function of coat proteins in vesicle formation? |
|
Definition
| Stabilizes membrane during budding; ATP required to strip coat away, exposing target information once formed. |
|
|
Term
| COPII vesicles typically form from what organelle? COPI? Clathrin? Exomer? |
|
Definition
| COPII: ER; COPI: Golgi, Clathrin: Golgi, Plama membrane; Exomer: Constitutive targeting to the plasma membrane |
|
|
Term
| How does an adapter select for lysosomal cargo? |
|
Definition
| ARF-1 (GTPase) is recruited to the membrane from the cytosol and is activated by ARF-GEF, then GGA and AP1 are recruited for target code recognition |
|
|
Term
| What are the three core components of vesicle targeting and fusion? |
|
Definition
| Small-GTPases of Rab family, tethering factors, SNARE and SNARE-associated proteins |
|
|
Term
| How does the Rab family of GTPases regulate vesicle delivery? |
|
Definition
| Rab is recruited to the membrane from the cytosol; in GTP-state, the tether is recruited, allowing SNARE association. |
|
|
Term
| What do 'tethers' (in vesicle trafficking) do? |
|
Definition
| Direct targeting and docking of transport containers. |
|
|
Term
| Describe 'tethers' (as in vesicle trafficking). |
|
Definition
| Group of proteins that interact with Rab and SNARE and facilitate 'tethering' of vesicles to acceptor membrane. |
|
|
Term
| Name the types of SNARES. |
|
Definition
| v-SNARES (vesicle) and t-SNARES (target) |
|
|
Term
| True or False. Specific SNARES and Rabs are localized to specific cellular compartments. |
|
Definition
|
|
Term
| Name three general mechanisms by which enzymatic action may be physiologically regulated. |
|
Definition
| Substrate concentration; quantity of enzyme present; reversible inhibition by products or other compounds; allosteric activation or inhibition; covalent modification; modulator protein binding; proteolytic cleavage |
|
|
Term
| True or False. In certain cases, proteolytic degradation is a reversible mechanism. |
|
Definition
| False. By definition, proteolytic degradation is irreversible. |
|
|
Term
| Define a zymogen and give two examples. |
|
Definition
| Larger, inactive precursor protein; pepsin, trypsin, chymotrypsin, prothrombin, and Factor X are examples. |
|
|
Term
| How are zymogens activated? |
|
Definition
| Activation of zymogen by proteolytic cleavage results in irreversible activation. |
|
|
Term
| Why are zymogens important in biological systems? |
|
Definition
| Allow proteins to be transported or stored in inactive forms that can be readily converted to active forms in response to some type of cellular signal. |
|
|
Term
| How are allosteric enzymes made to exert their function? |
|
Definition
| Function through reversible, non-covalent binding of a regulatory metabolite at a site other than the catalytic, active site. |
|
|
Term
| The velocity versus substrate plot of an enzymatic reaction you are studying has a sigmoidal curve. What does this denote? |
|
Definition
| Sigmoidal curves typically denote cooperative binding (the binding of one substrate unit facilitates the further binding of substrate) NOTE: Cooperative binding such as this often indicates that an enzyme may be dimeric |
|
|
Term
| What is the difference between homotropic and heterotropic regulation? |
|
Definition
| Homotropic: binding of one molecule to multi-subunit enzyme causes conformational shift affecting binding of SAME molecule to another subunit of enzyme; Heterotropic:…DIFFERENT… |
|
|
Term
| How do A-form and B-form kinases or synthases differ? |
|
Definition
|
|
Term
| What are the primary physiological (not, necessarily, biochemical) events that occur immediately after injury to a blood vessel occurs? |
|
Definition
| 1)Clumping of platelets at site of injury to create physical plug, 2)Vasoconstriction occurs to reduce blood flow through area, 3)Aggregation of fibrin into an insoluble clot that covers rupture (clot dissolved after actual repair of the blood vessel) |
|
|
Term
| What circulating protein mediates binding of platelets to collagen and one another? |
|
Definition
| von Willebrand factor (vWF) |
|
|
Term
| Describe the primary components of the enzyme amplification cascade resulting in the formation of fibrin. |
|
Definition
| Tissue Factor > allosteric activation of free TFVII(a) > activation of zymogen TFX(a) > FXa/FV(a) activates prothrombin to thrombin > Fibrinogen activated to fibrin |
|
|
Term
| How is the aggregated fibrin (soft clot) converted to a hard clot? |
|
Definition
| Thrombin activates factor XIII(a), the catalytic transglutamidase > catalyzes isopeptide bond |
|
|
Term
| Antithrombin III is a serpin. What is a serpin? |
|
Definition
| Proteins that serve as serine protease inhibitors. |
|
|
Term
| What does antithrombin III do? |
|
Definition
| Tightly binds and inactivates thrombin (allosteric inhibitor); later cleared from circulation in the liver. |
|
|
Term
| What is heparin administered clinically for, and how does it carry out its function? |
|
Definition
| Promotes assocation between antithrombin III and thrombin, used as an anticoagulant. |
|
|
Term
|
Definition
| An endothelial cell protein receptor with which thrombin forms complexes (in addition to cleaving fibrinogen). |
|
|
Term
| Thrombomodulin and calcium act as cofactors of thrombin activation of Protein C; when activated, what does Protein C do? |
|
Definition
| In conjunction with another protein cofactor (Protein S), it proteolyzes and inactivates Factors Va and VIIIa. |
|
|
Term
| What is fibrinolysis and how does it occur? |
|
Definition
| Dissolving of fibrin clots; Plasmin, circulating as plaminogen, is activated by tissue plasminogen activator (tPA); tPA proteolyzes plasminogen to plasmin, which then digests the fibrin. |
|
|
Term
| What keeps a single molecule of plasmin from rapidly and prematurely dissolving the entire fibrin clot? |
|
Definition
| After degrading a specific region, the digested peptides dissociate from the clot and take the plasmin-tPA complex with them. |
|
|
Term
| Some of the factors involved in clot formation contain a modified glutamate residue. What is it called and what is its function? |
|
Definition
| Carboxyglutamate; calcium chelator, associates with membrane to facilitate correct tertiary and quaternary folding of a protein. |
|
|
Term
| What is the basis for using dicoumarol and warfarin as anticoagulants? |
|
Definition
| These have been shown to inhibit formation of the carboxyglutamate residues of prothrombin and Factors VII, IX, and X (inhibiting their participation in the blood coagulation process). |
|
|
Term
| Theoretically, how many separate units would result from a single proteolytic cleavage event between two disulfide bonds? Two between two disulfide bonds? |
|
Definition
| One cleavage, one unit; two cleavages, two units |
|
|
Term
| The carboxyglutamate-rich residues from cleared thrombin travel to the liver and signal for the creation of new peptides. Why is this important to long-term therapies with vitamin K antagonists? |
|
Definition
| The vitamin K cycle (particularly its redox states) is vital to the formation of carboxyglutamate residues in the protein glutamyl carboxylation reaction. |
|
|
Term
| What a change in enthalpy during a chemical reaction indicate? |
|
Definition
| The energy released or absorbed by the reactant and product molecules as a result of changes in electronic bonding during a chemical reaction. |
|
|
Term
| A reaction with a decrease in enthalpy is characterized as ---thermic. |
|
Definition
|
|
Term
| True or false. If the ΔG for a reaction is positive, the reaction will occur spontaneously, without any additional energy input. |
|
Definition
| No. Positive indicates that energy input is required. A negative value would indicate a spontaneous, energy-releasing reaction. |
|
|
Term
| The actual free energy of ATP hydrolysis is large, but ATP has a reasonable level of stability. As a result, RAPID hydrolysis of ATP requires what class of molecule? |
|
Definition
|
|
Term
| Characterize the flow of electrons in an oxidation/reduction reaction. |
|
Definition
| Loss of electrons by species: oxidation; gain of electrons by species: reduction. |
|
|
Term
| In biological systems, oxidation is synonymous with what other reaction? |
|
Definition
| Dehydrogenation (loss of hydrogen) |
|
|
Term
| True or false. Nicotinamide adenine dinucleotide is a water-soluble coenzyme that undergoes reversible oxidation and reduction. |
|
Definition
|
|
Term
| What are monosaccharides and how are they named? |
|
Definition
| Simple sugar (single aldose or ketose unit); general classes named for number of carbons (pentose, hexose); glucose is the most abundant in nature. |
|
|
Term
| What are oligosaccharides? |
|
Definition
| Short chain of monosaccharides (<20); a common disaccharide is sucrose; components of glycoconjugates, oligosaccharides may contain branched structures. |
|
|
Term
| What are polysaccharides? |
|
Definition
| Loan chain of monosaccharides (>20); polysaccharides may contain branched structures; cellulose and glycogen are two common examples. |
|
|
Term
| Which glucose enantiomer is used in nature? |
|
Definition
|
|
Term
| How is a disaccharide constructed? |
|
Definition
| From two monosaccharides linked by an O-glycosidic bond. |
|
|
Term
| Bread is not sweet when you initially bite into it, but gradually becomes so after chewing. Why is this? |
|
Definition
| Amylase in the saliva forms maltose sugar from starch hydrolysis. |
|
|
Term
| What is another term for polysaccharides? |
|
Definition
|
|
Term
| What is a homopolysaccharide? What is a heteropolysaccharide? |
|
Definition
| Homo:single type of monosaccharide constituents, used for fuel storage (glycogen, starch) or structural elements (chitin, cellulose); Hetero: two or more different monosaccharides, components of ECM and associated with glycoconjugates. |
|
|
Term
| What does the acronym in 'GPI-anchor' stand for and what is the molecule's structure? |
|
Definition
| Glycosylphosphatidyl inositol; protein anchored to lipid via carbohydrate bridge. |
|
|
Term
| Generalized gangliosidosis results from a deficiency of what enzyme? What substrate(s) accumulates as a result? |
|
Definition
| Beta-galactosidase; ganglioside Gm1 |
|
|
Term
| Tay-Sachs results from a deficiency of what enzyme? What substrate(s) accumulates as a result? |
|
Definition
| Hexosaminidase A; ganglioside Gm2 |
|
|
Term
| Gaucher's results from a deficiency of what enzyme? What substrate(s) accumulates as a result? |
|
Definition
| Glucocerebrosidase; glucocerebroside (also known as glucosylceramide) |
|
|
Term
| Fabry's results from a deficiency of what enzyme? What substrate(s) accumulates as a result? |
|
Definition
| Alpha-galactosidase; globotriaosyceramide (also known as Gb3 or ceramide trihexoside) |
|
|
Term
| Sandhoff's results from a deficiency of what enzyme? What substrate(s) accumulates as a result? |
|
Definition
| Beta-hexosaminidase A and B; ganglioside Gm2 |
|
|
Term
| Neimann-Pick results from a deficiency of what enzyme? What substrate(s) accumulates as a result? |
|
Definition
| NP A&B: Acid sphingomyelinase; sphingomyelin |
|
|
Term
| Krabbe's disease results from a deficiency of what enzyme? What substrate(s) accumulates as a result? |
|
Definition
| Galactosylceramidase (β-galactocerebrosidase); galactocerebrosides |
|
|
Term
| Metachromatic leukodystrophy results from a deficiency of what enzyme? What substrate(s) accumulates as a result? |
|
Definition
| Arylsulfatase A; sulfatides |
|
|
Term
| How are the two classes of protein glycoconjugates characterized? |
|
Definition
| Proteoglycans: linear oligosaccharide chains, higher in carbohydrate content than glycoproteins; Glycoproteins branched, complex oligosaccharides, lower carbohydrate content than proteoglycans) |
|
|
Term
| True or False. Proteoglycan is another word for glycosaminoglycan. |
|
Definition
| False. A proteoglycan is a protein with covalently attached glycosaminoglycans. |
|
|
Term
| Chondroitin sulfate, keratan sulfate, and heparan sulfate are all… |
|
Definition
|
|
Term
| What makes up hyaluronic acid? |
|
Definition
| Glycosaminoglycan and N-acetylglucosamine |
|
|
Term
|
Definition
| Iduronic acid (primarily) or glucuronic acid and sulfated N-acetylglucosamine. |
|
|
Term
| Chondroitin sulfate is composed of what? |
|
Definition
| Glucuronic acid and sulfated N-acetylglucosamine. |
|
|
Term
| What does the term aggrecan indicate? |
|
Definition
| Large, aggregating proteoglycan; protein modified with carbohydrates; highly negatively charged, form a 'gel' when water absorbed. |
|
|
Term
| How are chondrodystrophies characterized? |
|
Definition
| Normal-sized trunk with abnormally shortened limbs and extremities, and early osteoarthritic onset. |
|
|
Term
| How are the mucopolysaccharidoses characterized? |
|
Definition
| Accumulation and excretion (through urine) of oligosaccharides from glycosaminoglycan. |
|
|
Term
| What do the mucopolysaccharidoses typically result from? |
|
Definition
| Genetic deficiency in one or a combination of hydrolases that breakdown heparin sulfate, dermatan sulfate |
|
|
Term
| What does 'N' in an N-linked glycoprotein stand for? |
|
Definition
| Nitrogen, NOT asparagine. |
|
|
Term
| What is the structure of an N-linked glycoprotein? |
|
Definition
| N-linked glycans are bound to the amide nitrogen of asparagine side chains. |
|
|
Term
| True or False. There is no template for N- or O-linked glycans. |
|
Definition
|
|
Term
| What does the 'O' in an O-linked glycoprotein stand for? |
|
Definition
|
|
Term
| What is the structure of an O-linked glycoprotein? |
|
Definition
| O-linked glycans are bound to the hydroxy oxygen of Ser and Thr. |
|
|
Term
| What is the difference between a synthase and a synthetase? |
|
Definition
| Synthase catalyzes condensation reaction; synthetase catalyzes condensation reactions requiring ATP or another nTP |
|
|
Term
| What do kinases and phosphatases do? |
|
Definition
| Kinase catalyzes phosphorylation, transfer of phosphoryl from ATP to an acceptor; phosphatase catalyzes removal of phosphoryl group from a phosphate ester. |
|
|
Term
| What do dehydrogenases do? |
|
Definition
| Catalyze the removal of pairs of hydrogen atoms. |
|
|
Term
| What are the three primary regulatory enzymes of glycolysis? |
|
Definition
| Hexokinase, phosphofructokinase-1 (6-phosphofructo-1-kinase), pyruvate kinase |
|
|
Term
| What enzyme catalyzes this glycolytic reaction? Glucose>Glucose-6-phosphate |
|
Definition
|
|
Term
| What enzyme catalyzes this glycolytic reaction? Glucose-6-phosphate>Fructose-6-phosphate |
|
Definition
| Glucose-6-phosphate isomerase (phosphohexo isomerase) |
|
|
Term
| What enzyme catalyzes this glycolytic reaction? Fructose-6-phosphate>Fructose1,6-bisphosphate |
|
Definition
| Phosphofructokinase-1 (6-phosphofructo-1-kinase) |
|
|
Term
| What enzyme catalyzes this glycolytic reaction? Fructose-1,6-bisphosphate > dihydroxyacetone-phosphate + glyceraldehyde-3-phosphate |
|
Definition
|
|
Term
| What enzyme catalyzes this glycolytic reaction? Dihydroxyacetone-phosphate > glyceraldehyde-3-phosphate |
|
Definition
| Triose phosphate isomerase |
|
|
Term
| What enzyme catalyzes this glycolytic reaction? Glyceraldehyde-3-phosphate>1,6-bisphosphoglycerate |
|
Definition
| Glyceraldehyde-3-phosphate dehydrogenase (NADH formed at this step) |
|
|
Term
| What enzyme catalyzes this glycolytic reaction? 1,3-bisphosphoglycerate>3-phosphoglycerate |
|
Definition
| Phosphoglycerate isomerase, also called phosphoglycerate kinase (ATP formed at this step) |
|
|
Term
| What enzyme catalyzes this glycolytic reaction? 3-phosphoglycerate>2-phosphoglycerate |
|
Definition
|
|
Term
| What enzyme catalyzes this glycolytic reaction? 2-phosphoglycerate>phosphoenolpyruvate |
|
Definition
|
|
Term
| What enzyme catalyzes this glycolytic reaction? Phosphoenolpyruvate>pyruvate |
|
Definition
| Pyruvate kinase (ATP formed at this step) |
|
|
Term
| What reaction does this glycolytic enzyme catalyze? Hexokinase |
|
Definition
| Glucose>glucose-6-phosphate |
|
|
Term
| What reaction does this glycolytic enzyme catalyze? G6P isomerase/phosphohexo isomerase |
|
Definition
| Glucose-6-phosphate>fructose-6-phosphate |
|
|
Term
| What reaction does this glycolytic enzyme catalyze? Phosphofructokinase-1/6-phosphfructo-1-kinase |
|
Definition
| Fructose-6-phosphate>fructose-1,6-bisphosphate |
|
|
Term
| What reaction does this glycolytic enzyme catalyze? Aldolase |
|
Definition
| Fructose-1,6-bisphosphate>Dihydroxyacetone phosphate + glyceraldehyde-3-phosphate |
|
|
Term
| What reaction does this glycolytic enzyme catalyze? Triose phosphate isomerase |
|
Definition
| Dihydroxyacetone phosphate>glyceraldehyde-3-phosphate |
|
|
Term
| What reaction does this glycolytic enzyme catalyze? G3P dehydrogenase |
|
Definition
| Glyceraldehyde-3-phosphate>1,6-bisphosphoglycerate (NADH also generated in this reaction) |
|
|
Term
| What reaction does this glycolytic enzyme catalyze? Phosphoglycerate isomerase |
|
Definition
| 1,6-bisphosphoglycerate>3-phosphoglycerate (ATP also generated in this reaction) |
|
|
Term
| What reaction does this glycolytic enzyme catalyze? Phosphoglycerate mutase |
|
Definition
| 3-phosphoglycerate>2-phosphoglycerate |
|
|
Term
| What reaction does this glycolytic enzyme catalyze? Enolase |
|
Definition
| 2-phosphoglycerate>phosphoenolpyruvate |
|
|
Term
| What reaction does this glycolytic enzyme catalyze? Pyruvate kinase |
|
Definition
| Phosphoenolpyruvate>pyruvate (ATP also generated in this reaction) |
|
|
Term
| Temporally important as the initiating glycolytic step, why is the reaction catalyzed by hexokinase spatially important to the cell? |
|
Definition
| Conversion of glucose to glucose-6-phosphate 'traps' the glucose molecule in the cell (cannot cross the membrane again) |
|
|
Term
| How do mercury-containing compounds inhibit glycolysis? |
|
Definition
| Bind sulfhydryl group in active site of glyceraldehyde-3-phosphate dehydrogenase |
|
|
Term
| Kinases typically phosphorylate a substrate. How, then, does phosphoglycerate kinase convert 1,3-bisphosphoglycerate to 3-phosphoglycerate? |
|
Definition
| It is named for the reverse reaction, initially characterized in vitro. |
|
|
Term
| True or False. Arsenate does not inhibit glycolysis. |
|
Definition
| True. It only prevents ATP production in glycolysis. |
|
|
Term
| How does Arsenate interfere with glycolysis? |
|
Definition
| Arsenate substitutes for a phosphate in the G3P dehydrogenase reaction. 3-phosphoglycerate is formed and glycolysis continues, but the phosphoglycerate kinase step is bypassed and ATP is not produced. |
|
|
Term
| What is the glycolytic-inhibitory mechanism of fluoride poisoning? Why is this important in the diagnosis of diabetes? |
|
Definition
| Enolase is inhibited by fluoride; used to prevent additional glycolysis when testing blood glucose levels of a sample. |
|
|
Term
| How is the PEP>pyruvate reaction prevented from going in reverse? |
|
Definition
| Pyruvate kinase catalyzes the formation of the enol form of pyruvate; the enol form then spontaneously converts to the more stable keto form by tautomerization. The keto form cannot readily be tautomerized back to the enol form, thus stabilizing the reaction in the forward direction. |
|
|
Term
| How is hexokinase used to regulate glycolysis? |
|
Definition
| Hexokinase is allosterically inhibited by glucose-6-phosphate. Multiple isozymes of hexokinase are also expressed in different tissues and organs (providing a second level of regulation) |
|
|
Term
| How do the hexokinase isozymes in the liver and the skeletal muscle differ? |
|
Definition
| Glucokinase in the liver exhibits lower enzymatic activity than hexokinase in skeletal muscle. |
|
|
Term
| How is pyruvate kinase used to regulate glycolysis? |
|
Definition
| Pyruvate kinase is allosterically inhibited by ATP, acetyl-CoA, and long chain fatty acids. |
|
|
Term
| How is phosphofructokinase-1 used to regulate glycolysis? |
|
Definition
| ATP inhibits, AMP/ADP and fructose-2,6-bisphosphate promote. |
|
|
Term
| How are 6-phosphofructo-2-kinase and fructose-2,6-bisphosphate related? |
|
Definition
| They are found on the same polypeptide chain; regulated by phosphorylation: (+P, 6-PF-2-Kb/F-2,6-BP'ase a) and (-P, 6-PF-2-Ka/F-2,6-BP'ase b) |
|
|
Term
| What effect on glycolysis does glucagon and epinephrine have in the liver? |
|
Definition
| Glucagon and epinephrine increase cAMP; cAMP activates PKA; PKA decreases F-2,6-BP levels, making F6P to F16BP transition less favorable. |
|
|
Term
| What effect does insulin have on glycolysis in the liver? |
|
Definition
| Insulin decreases cAMP and inhibits PKA; insulin activates phosphoprotein phosphatase, which activates 6-PF-2-K, increasing the glycolytic rate. |
|
|
Term
| What effect does epinephrine have on glycolysis in the heart? |
|
Definition
| Different 6-PF-2-K/F-2,6-BP'ase isozyme in heart than liver; epinephrine increases cAMP, activating PKA, activating 6-PF-2-K. Essentially opposite effects in muscle and liver. |
|
|
Term
| What are the major substrates of gluconeogenesis? |
|
Definition
| Glucogenic amino acids, lactate, glycerol, and propionate. |
|
|
Term
| Where does gluconeogenesis predominantly occur? |
|
Definition
|
|
Term
| Which amino acids are glucogenic? |
|
Definition
| All but leucine and lysine. |
|
|
Term
| PEP>pyruvate is an irreversible glycolytic reaction. How does this reaction go in reverse in gluconeogenesis? |
|
Definition
| Pyruvate>oxaloacetate via pyruvate carboxylase, then oxaloacetate>PEP via PEP carboxykinase. |
|
|
Term
| F6P to F-1,6-BP is an irreversible glycolytic reaction. How does this reaction go in reverse in gluconeogenesis? |
|
Definition
| F-1,6,-BP>F6P via F-1,6,-bisphosphatase |
|
|
Term
| Glucose to G6P is an irreversible glycolytic reaction. How does this reaction go in reverse in gluconeogenesis? |
|
Definition
|
|
Term
| What role does biotin play in gluconeogenesis? |
|
Definition
| Biotin is covalently bound to pyruvate carboxylase and is a carrier of activated CO2. Carboxyl group transferred from bicarbonate to biotin, forming carboxybiotin-pyruvate carboxylase intermediate. Carboxyl group then transferred to pyruvate to form oxaloacetate. Biotin functions as an enzyme. |
|
|
Term
| Glucose-6-phosphatase overcomes what irreversible glycolytic step? |
|
Definition
| Glucose>Glucose-6-phosphate |
|
|
Term
| What two enzymes are important in converting pyruvate to oxaloacetate and acetyl-CoA and how do they affect one another? |
|
Definition
| Converted to oxaloacetate by pyruvate carboxylase or converted to acetyl-CoA by pyruvate dehydrogenase. Acetyl-CoA allosterically stimulates pyruvate carboxylase and allosterically inhibits pyruvate dehydrogenase. |
|
|
Term
| F-2,6-BP is a derivate of what glycolytic intermediate? |
|
Definition
|
|
Term
| What effect does glucagon and epinephrine have on gluconeogenesis in the liver? |
|
Definition
| Increase cAMP, which activates PKA, which activates F-2,6-BP'ase, which decreases F-2,6-BP levels. |
|
|
Term
| What effect does insulin have on gluconeogenesis in the liver? |
|
Definition
| Insulin decreases cAMP and inhibits PKA; insulin activates phosphoprotein phosphatase, which activates 6-PF-2-K, increasing the glycolytic rate and decreasing gluconeogenesis. |
|
|
Term
| What effect does epinephrine have on gluconeogenesis in the heart? |
|
Definition
| No effect; gluconeogenesis DOES NOT occur here. |
|
|
Term
| What effect do glucagon, glucocorticoids, and thyroid hormones have on PEPCK? |
|
Definition
|
|
Term
| What effect does insulin have on PEPCK? |
|
Definition
|
|
Term
| What is the benefit of receptor/ligand concentration in receptor-mediated endocytosis? |
|
Definition
| Concentration allows regulated entry of fluids. |
|
|
Term
| What data suggest that clathrin-coated pits may be held in place by the cytoskeletal system? |
|
Definition
| Time lapse photography that shows the pits disappearing and reappearing, usually in the same spots. |
|
|
Term
| How do receptors 'know' to localize to a clathrin coated pit? |
|
Definition
| Receptor signal sequences bind adaptin molecules, facilitated by Beta-arrestins. This stops the receptor, concentrating it inside the pit, and also stimulates more clathrin to accumulate. |
|
|
Term
| A patient has high serum cholesterol as a result of a defective LDL receptor. What is the most likely defect? |
|
Definition
| Defect preventing receptor binding to Adaptin-2; receptor may enter clathrin coated pit, but won't stay. |
|
|
Term
| Neimann-Pick type C arises from a mutation in the NPC1 protein. What does this protein normally do and what happens in the disease? |
|
Definition
| Normally needed for cholesterol transport, cholesterol accumulates in late endosomes. |
|
|
Term
| Where are sperm mitochondria located? |
|
Definition
|
|
Term
| Briefly characterize the malate-aspartate shuttle. |
|
Definition
| 'Transport' NADH produced in glycolysis into the mitochondrial matrix for the ETC. |
|
|
Term
| True or False. In the electron transport chain, electrons first flow from complex I to complex II. |
|
Definition
| False. May go from CI OR CII to CIII via coenzyme Q |
|
|
Term
| What is another name for Coenzyme Q? |
|
Definition
|
|
Term
| How many protons are pumped into the intermembrane space by Complex II? |
|
Definition
| None, CII is not a proton pump. |
|
|
Term
| Describe the structure of the ATP synthase complex. |
|
Definition
| F1 particle composed of three alpha-beta dimers with central gamma rod. F0 transmembrane ring-shaped particle composed of c subunits. |
|
|
Term
| What particle of Complex V actually makes ATP? |
|
Definition
|
|
Term
| How might dinitrophenol be used as a diet drug and why is it illegal? |
|
Definition
| Artifically uncouples oxidative phosphorylation, allowing ETC to continue; transports H+ back across the inner membrane. Generates LOTS of heat and can be fatal. |
|
|
Term
| How does fluoroacetate exert its primary effect as a metabolic poison? |
|
Definition
| Combines with coenzyme A to form fluoroacetyl CoA, which is substituted for acetyl CoA. |
|
|
Term
| How does malonate exert its primary effect as a metabolic poison? |
|
Definition
| Binds succinate dehydrogenase but does not reaction, effectively inhibiting succinate. |
|
|
Term
| How does rotenone exert its primary effect as a metabolic poison? |
|
Definition
| Inhibits electron transfer from complex I to ubiquinone. |
|
|
Term
| What effect does carbon monoxide have on metabolism? |
|
Definition
| Bind complex IV (cytochrome oxidase) of ETC. |
|
|
Term
| How does antimycin A exert its primary effect as a metabolic poison? |
|
Definition
| Inhibits complex III of ETC. |
|
|
Term
| What effect does cyanide have on metabolism? |
|
Definition
| Bind complex IV (cytochrome oxidase) of ETC. |
|
|
Term
| What are some other names for the pentose phosphate pathway? |
|
Definition
| Hexose monophosphate shunt; hexose monophosphate pathway; 6-phosphogluconate pathway |
|
|
Term
| What are the main functions of the pentose phosphate pathway? |
|
Definition
| Generation of NADPH and ribose residues. |
|
|
Term
| What is the primary production phase of the pentose phosphate pathway? |
|
Definition
| Oxidative phase (as opposed to the non-oxidative phase) |
|
|
Term
| What is the major site of regulation of the pentose phosphate pathway? |
|
Definition
| Reaction 1, glucose-6-phosphate dehydrogenase. |
|
|
Term
| What is the primary purpose of the non-oxidative phase of the pentose phosphate pathway? |
|
Definition
| Regeneration of Glucose-6-phosphate |
|
|
Term
| How might a deficiency in glucose-6-phosphate dehydrogenase present as hemolytic anemia? |
|
Definition
| Reduced NADPH levels and reduced glutathione production results in increased erythrocytic breakdown as a result of radical oxygen species. |
|
|
Term
| True or False. Mitochondrial DNA is localized within the nucleus as a mitochondrial organizing center. |
|
Definition
| False. mtDNA is housed within the mitochondria itself. |
|
|
Term
| How is a protein imported into the mitochondria? |
|
Definition
| Uncoiling via chaperones, positive signal sequence binds TOM receptors and moves through TOM/TIM guides (positive net charge, electrochemical gradient. |
|
|
Term
| Describe the so-called 'mitochondrial bottleneck.' |
|
Definition
| Initially large number of oogonia, divide and form primary oocyte; by maturation, significant reductions by formation of mature preovulatory oocyte, mutant strands of mtDNA may be highly concentrated. |
|
|
Term
| What are ragged red fibers? |
|
Definition
| Indicative of mitochondrial myopathy upon muscle biopsy using modified trichrome stain (accumulation of abnormal mitochondria apparent). |
|
|
Term
| True or False. Glucose 6-P, fructose 6-P, and mannose 6-P can interconvert directly. |
|
Definition
|
|
Term
| Why is aldolase B the rate-limiting enyme in fructose metabolism? |
|
Definition
| Aldolase B generates dihydroxyacetone phosphate and glyceraldeyde from fructose-1-phosphate, but affinity of aldolse B for F-1-P is much poorer than for F-1,6-BP. |
|
|
Term
| What enzyme is deficient in essential fructosuria and what are some symptoms? |
|
Definition
| Fructokinase; asymptomatic |
|
|
Term
| What enzyme is deficient in hereditary fructose intolerance and what is its primary pathology? |
|
Definition
| Aldolase B; Fructose consumption results in accumulation of F-1-P and depletion of Pi and ATP in the liver. |
|
|
Term
| Why does hereditary fructose intolerance typically present in very young children? |
|
Definition
| Asymptomatic and healthy until fructose or sucrose is ingested (fine on milk, but fruit, cereal, or formula may induce jaundice, hepatomegaly, vomiting, and convulsions) |
|
|
Term
| Differentiate Type 1a CDGS and 1b CDGS. |
|
Definition
| Carbohydrate-deficient glycoprotein syndrome; 1a: phosphomannosemutase 2 mutase, neurologic abnormalities; 1b: phosphomannose isomerase, hepatic fibrosis. |
|
|
Term
| What basic defect are the CDGSs thought to result from? |
|
Definition
| Defect in synthesis or processing of N-linked oligosaccharides. |
|
|
Term
| How might cataracts result from having diabetes? |
|
Definition
| High [glc] in the lens, aldose reductase converts some to sorbitol, to be converted to fructose; accumulation of sorbitol causes aggregation and denaturation. |
|
|
Term
| Name three separate enyzymes whose deficiencies may result in galactosemia. |
|
Definition
| Galactose-1-phosphate uridyl transferase deficiency: cataracts, mental retardation, liver damage; UDP-glucose-4-epimerase may be benign if limited to blood cells; galactokinase may be relatively mild, with early cataract formation. |
|
|
Term
|
Definition
| Derived from heme catabolism, poorly soluble in water and carried bound to albumin, high concentration causes transfer to lipids and toxicity (kenicterus), taken up by liver cells to form bilirubin diglicuronide which is excreted in bile and urine. |
|
|
Term
| Having a specific blood group results from the addition of --- to ceramide members of the cell membrane. |
|
Definition
|
|
Term
| Phosphomannose isomerase converts mannose 6-P to… |
|
Definition
|
|
Term
| Phosphomannose mutase 2 converts mannose 6-P to… |
|
Definition
|
|
Term
| Give three reasons for storing excess glucose calories as glycogen rather than fat. |
|
Definition
| 1) fat cannot be mobilized as rapidly as glycogen, 2) fat cannot be used as an energy source in the absence of oxygen, 3) fat cannot be converted to glucose to maintain BG levels required by brain |
|
|
Term
| Why is it not physiologicaly feasible to store glucose as free glucose (as opposed to glycogen)? |
|
Definition
| Glucose is osmotically active; would require energy to pump against the gradient to concentration, and would likely result in cellular lysis. |
|
|
Term
| What enzyme initiates glycogenolysis? |
|
Definition
|
|
Term
| Glycogen phosphorylase acts repetitively on the nonreducing end of glycogen until 4 residues away from an alpha-1,6 branch point. What next? |
|
Definition
| DE transferase activity removes three glucosyl residues and attaches to primary branch, DE glucosidase activity hydrolyzes alpha-1,6 linkage of single remaining glycosyl residue. |
|
|
Term
| Upon formation of an amylose chain of at least 11 residues, what enyme continues glycogenesis and how does it do so? |
|
Definition
| 1,4-alpha-glucan branching enzyme; removes block ~7 residues from growing chain and transfers to another chain to produce alpha-1,6 linkage. |
|
|
Term
| Glycogen phosphorylase a is inhibited by ---. The b form is greatly stimulated by ---. |
|
Definition
|
|
Term
| What are the most commonly affected tissues in glycogen storage disorders? |
|
Definition
| Liver and muscle; they have abundant glycogen |
|
|
Term
| Von Gierke arises from what enzymatic deficiency? What is its pathology? |
|
Definition
| Glucose 6-phosphatase deficiency; Severe hypoglycemia, liver unable to produce free glucose. |
|
|
Term
| Why does hepatomegaly arise as a result of Von Gierke's disease? |
|
Definition
| Abnormally increased glycogen storage |
|
|
Term
| McArdle's disease arises from what enzymatic deficiency? What is its pathology? |
|
Definition
| Myophosphorylase deficiency; results in decreased ATP production |
|
|
Term
| What is the function of triacylglycerol lipase? |
|
Definition
| Hydrolyze triacylglycerol, mobilize fat in adipose tissue. |
|
|
Term
| How are free fatty acids transported in blood? |
|
Definition
|
|
Term
| What are the three stages of fatty acid oxidation? |
|
Definition
| 1)activation of fatty acids to acyl-CoA, 2)carnitine shuttle, 3) and beta-oxidation. |
|
|
Term
| Why is the carnitine shuttle necessary in beta-oxidation of fatty acids? |
|
Definition
| FA can only enter the inner mitochondrial membrane as carnitive derivatives |
|
|
Term
| Characterize FA beta-oxidation. |
|
Definition
| Successive cleavage of 2-carbon units with release of acetyl-CoA (carried out by Acyl-CoA dehydrogenase, Enoyl-Coa hydratase, Hydroxyacyl-Coa-dehydrogenase, and Thiolase |
|
|
Term
| Characterize FA alpha-oxidation. |
|
Definition
| Removal of one C at a time from the carboxyl end of the molecule, does not generate NADH or NADPH. |
|
|
Term
| When does liver ketogenesis occur? |
|
Definition
| Occurs when there is a high rate of fatty acid oxidation in the liver, ketone bodies exported as energy source. |
|
|
Term
| How are lipogenesis and ketogenesis regulated? |
|
Definition
| 1)adipose tissue: glucagon and epinephrine activate hormone sensitive lipase, 2)liver mitochondria: regulation of entry of long-chain acyl groups into mitochondria, 3)acetyl-CoA is formed from beta-oxidation |
|
|
Term
| How might fatty acids play a role in SIDS? |
|
Definition
| Sudden infant death syndrome; deficiency of medium-chain FA actyl-CoA dehydrogenase, leading to hypoketotic hypoglycemia |
|
|
Term
| Zellweger's syndrome results from what defect? |
|
Definition
| Inherited absence of peroxisomes in all tissues, accumulation of branched chain acids in plasma and brain tissues |
|
|
Term
| Refsum's disease results from the buildup of what substances? |
|
Definition
| Phytanic acids, formed from phytol (a constituent of chlorophyll) |
|
|
Term
| Dicarboxylic aciduria is a deficiency of what enzyme? |
|
Definition
| medium-chain acyl-CoA dehydrogenase |
|
|
Term
| What is the difference between endocrine, paracrine, and autocrine signaling. |
|
Definition
| Endocrine: long-distances, typically travels through circulation; paracrine: nearby, neighboring target; autocrine: self-targeting. |
|
|
Term
| Characterize the protein structure important to gap junctions. |
|
Definition
| Six connexins making up a single connexon with central channel. |
|
|
Term
| True or false. Most phospholipids contain only one type of fatty acid per molecule. |
|
Definition
| False. Most contain more than one type. |
|
|
Term
| Etanolamine plasmalogens occur in --- while choline plasmalogens are abundant in ---. |
|
Definition
|
|
Term
| Where is dipalmitoyllecithin found in the body and what is its primary function? |
|
Definition
| Surfactant component necessary for normal lung function; decreases surface tension of lung fluid layer, prevents atelectasis at the end of the expiration phase of breathing. |
|
|
Term
| Where is dipalmitoyllecithin produced? |
|
Definition
| Produced by Type II pneumocyte with lamellar bodies in the lung; surfactant also contains phosphatidylglycerol, phosphatidylinositol |
|
|
Term
| When does the fetal lung's transition from sphingomyelin to surfactant occur and what cell plays the primary role? |
|
Definition
| Sphingomyelin ,<28 weeks; @24th week, type II pneumocytes appear and produce lamellar bodies; 32nd week, surfactant appears in lung and amniotic fluid. |
|
|
Term
| In most cells the pathway for phospholipid synthesis starts from sn-glycerol 3-phosphate. What glycolytic intermediate is this derived from in adipose? What is its derivative in liver and kidney? |
|
Definition
| Dihydroxyacetone phosphate (in adipocytes), Phosphorylation of glycerol by glycerol kinase in liver and kidney. |
|
|
Term
| What enzyme converts phosphocholine to CDP-choline? Where is this enzyme typically found and how is it activated/inactivated? |
|
Definition
| Phosphocholine cytidyltransferase; exists in active, membrane-bound form associated with ER and inactive, cytosolic form. Inactivated by cAMP-dependent phosphorylation and activated by dephosphorylation and fatty-acyl CoA. |
|
|
Term
| In liver, phosphatidylcholine is derived by… |
|
Definition
| …repeated methylation of phosphatidylethanolamine. |
|
|
Term
| What is SAM and PAPS and in what biosynthetic process are they important? |
|
Definition
| S-adenosylmethionine, methyl donor and 3'-phosphoadenosine-5'phosphosulfate, sulfate donor, both involved in membrane lipid synthesis. |
|
|
Term
| Sphingolipids are a class of complex lipids whose core structure is… |
|
Definition
| …the amino alcohol sphingosine. |
|
|
Term
| Ceramides are fatty acid amide derivatives of… |
|
Definition
|
|
Term
| Sphingomyelin is a major component of membranes of… |
|
Definition
|
|
Term
| Beta-glucocerebrosidase deficiency, with accumulated glucocerebroside in the bone marrow, spleen, and macrophages is characteristic of what disease? |
|
Definition
|
|
Term
| Beta-galactocerebrosidase deficiency, with impaired myelin growth/maintenance and accumulated galactocerebrosides is characteristic of what disease? |
|
Definition
| Globoid leukodystrophy or Krabbe's disease |
|
|
Term
| Lysosomal sulfphatase deficiency, with the accumulation of sulphogalactocerebroside, is characteristic of what disease? Where does the disease gets its name? |
|
Definition
| Metachromatic leukodystrophy; yellow staining of nerve with cresyl violet (metachromasia) |
|
|
Term
| Angiokeratomas and kidney failure are characteristic of this disease, resulting from mutation in the alpha-galactosidase gene. What substrate accumulates in the disease? |
|
Definition
| Fabry disease; ceramide trihexoside accumulation |
|
|
Term
| What is the name for acid glycosphingolipids containing sialic acid? |
|
Definition
|
|
Term
| Beta-hexosaminidase deficiency leads to GM2 gangliosidosis with mental retardation, a characteristic cherry red macula, and hepatomegaly. What is the name for this disease? |
|
Definition
|
|
Term
| Cholera toxin is a protein secreted by the pathogen Vibrio cholera, and results in Cl- secretion (followed by water) leading to diarrhea. How does this occur? |
|
Definition
| The toxin has an alpha and a beta subunit; the beta subunit binds gangliosides and allows entry of alpha into the cell; alpha is ADP-ribosyltransferase of G protein with activation of adenylate cyclase, stimulating Cl- secretion. |
|
|
Term
| The structure of a fatty acid is… |
|
Definition
| Long hydrocarbon chain with terminal carboxylate group. |
|
|
Term
| Fatty acids supply the majority of energy to what organ? |
|
Definition
|
|
Term
| ω-3 fatty acids are essential for development of what system? |
|
Definition
|
|
Term
| True or False. Some fatty acids regulate gene expression. |
|
Definition
|
|
Term
| High levels of trans-unsaturated fatty acids in the diet are considered unsafe. Why is this? |
|
Definition
| Compete with cis-FA, are metabolized more like saturated than like cis-unsaturated, do not possess essential FA activity, may antagonize metabolism of essential FA, raise plasma LDL and lower HDL. |
|
|
Term
| A diet that is low in fat and/or high in carbohydrates or proteins is likely to encourage… |
|
Definition
|
|
Term
| Fatty acids are synthesized from --- by the fatty acid synthase complex. |
|
Definition
|
|
Term
| What is the major enzyme regulated in fatty acid synthesis and what does it do? |
|
Definition
| Acetyl-CoA carboxylase; catalyzes conversion of acetyl-CoA to malonyl-CoA |
|
|
Term
| How do insulin, glucagon, and epinephrin individually affect acetyl-CoA carboxylase? What biosynthetic mechanism is regulated? |
|
Definition
| Insulin, UP; glucagon/epinephrine, DOWN; fatty acid synthesis is mechanism regulated by acetyl-CoA |
|
|
Term
| How does acetyl-CoA cross the inner mitochondrial membrane into the cytosol? |
|
Definition
| Conjugated with oxaloacetate to form citrate, transported by malate-citrate antiporter. |
|
|
Term
| In mitochondrial and ER fatty acid synthesis, what is used as the acetyl donor? |
|
Definition
|
|
Term
| Triacylglycerols are synthesized in what tissues? |
|
Definition
|
|
Term
| Synthesis of one triacylglycerol molecule requires… |
|
Definition
| …three fatty acid molecules and one molecule glycerol-3-phosphate. |
|
|
Term
| In the liver, glycerol is phosphorylated by glycerol kinase to glycerol-3-phosphate for traicylglycerol synthesis. What is the source in adipose tissue? |
|
Definition
| Glucose via dihydroxyacetone phosphate (glycerol kinase is not present) |
|
|
Term
| In the fed state, there is net deposition of triacylglycerol in… |
|
Definition
|
|
Term
| Characterize the free fatty acid levels in obesity thought to contribute to the development of insulin resistance and Type 2 diabetes? |
|
Definition
| ELEVATED concentrations are thought to contribute |
|
|
Term
| What events directly follow receptor binding of a ligand in RTK signaling? |
|
Definition
| Receptor tyrosine kinase; ligand binding results in receptor dimerization and (auto)crossphosphorylation of selective tyrosine residues on the intracellular portion. |
|
|
Term
| These domains bind specific phosphorylated tyrosines in the cytoplasmic portion of RTK receptors. |
|
Definition
|
|
Term
| Briefly characterize RTK activation of PI3-Kinase. |
|
Definition
| Binding of ligand, dimerization/crossphosphorylation of receptors, binding by PI3-kinase. |
|
|
Term
| Briefly characterize RTK activation of PLC-gamma and its direct effects. |
|
Definition
| Upon ligand binding and autophosphorylation of receptor, PLC-gamma binds receptor and catalyzes conversion of PIP2 to free IP3 and membrane-bound diacylglycerol |
|
|
Term
| What direct effect does RTK-dependent upregulation of IP3 have? |
|
Definition
| Binding to IP3 receptor of ER, promoting calcium release. |
|
|
Term
| What direct effect does RTK-dependent upregulation of DAG have? |
|
Definition
| Activation of protein kinase C |
|
|
Term
| Briefly characterize RTK-Ras-GAP activation. |
|
Definition
| Grb2 adapter protein (SH2 domain) bound to SOS (GEF), swaps GDP on inactive Ras to GTP on active Ras (activation of Raf GTPase).Raf > MEK > ERK. |
|
|
Term
| How is the Tel/PDGFR oncogene activated? |
|
Definition
| Improper folding of receptor portion leads to constitutive kinase activation. |
|
|
Term
| Briefly characterize RSK signaling. |
|
Definition
| Ligand binds type II receptor, which recruits type I receptor, which phosphorylates Smad(x… number depends on specific signaling molecule), at which time SmadIV cofactor facilitates formation of the transcriptional complex. |
|
|
Term
| What is fibrodysplasia ossificans progressiva (FOP)? |
|
Definition
| Disease caused by activating point mutation in GS domain of Type I receptor, ALK 2; pre-muscle cells become bone. |
|
|
Term
| Name the general classes of hormones. |
|
Definition
| Peptide and protein hormones; tyrosine derivatives (including thyroid, catecholamines epinephrine and norepinephrine); and steroid hormones (sex, progestational, adrenocortical) |
|
|
Term
| Steroid hormones are derived from… |
|
Definition
|
|
Term
| Adrenocorticotropic hormone (ACTH) stimulates cells in the adrenal cortex to increase production and secretion of… |
|
Definition
|
|
Term
| Gonadotropin-Releasing hormone is released by… |
|
Definition
|
|
Term
| GnRH acts on gonadotrope cells of the anterior pituitary to stimulate release of… |
|
Definition
| …follicle-stimulating hormone (FSH) and luteininzing hormone (LH). |
|
|
Term
| What hormone is released by the hypothalamus and acts on somatotropes of the anterior pituitary gland to stimulate release of GH? |
|
Definition
| Growth hormone releasing hormone |
|
|
Term
| Growth hormone releasing (GIH) or somatostatin is released by the --- to inhibit release of GH. |
|
Definition
|
|
Term
| What two hormones are synthesized by hypothalamic neurons and stored in the neurohypophysis? |
|
Definition
|
|
Term
| What two types of receptors have the potential to induce release of vasopressin and neurophysin II? What stimulates them? |
|
Definition
| Baroreceptors responding to a fall in blood pressure, Osmoreceptors respond to an increase in extracellular salt concentration. |
|
|
Term
| What is the primary target organ for vasopressin? |
|
Definition
|
|
Term
| What effect does vasopressin have in the kidney? |
|
Definition
| Increases water reabsorption by the kidney distal tubule cells; translocation of water channels called aquaporins. |
|
|
Term
| What disorder may arise as consequence of vasopressin or aquaporin mutations? |
|
Definition
| Diabetes insipidus, increased thirst and large volume of hypoosmolar urine excretion. |
|
|
Term
| What occurs upon the release of renin-containing granules by juxtaglomerular cells upon detection of hypovolemia? |
|
Definition
| Renin proteolyzes angiotensinogen (produced in liver) to Angiotensin I. Angiotension converting enzyme (ACE) in the lung converts AI to AII, aminopeptidase converts AII to AIII. II and III bind Ar in glomerulosa cell of adrenal gland and release aldosterone via IP3 signaling. |
|
|
Term
| True or False. The primary (classical) intracellular response to steroid hormone involves signal amplification via kinase cascades. |
|
Definition
| False. No signal amplification is present; steroid hormone-receptor complexes activate primary response genes. |
|
|
Term
| True or False. The classical action of steroid hormone can also be called ligand-dependent DNA binding. |
|
Definition
|
|
Term
| True or False. The Non-classical nuclear receptor gene transcription pathway can also be called ligand-dependent DNA binding. |
|
Definition
| False. Ligand-INDEPENDENT DNA binding. |
|
|
Term
| In ligand-indendependent DNA binding, what coenzymes are present on the receptor with and without the hormone's presence. |
|
Definition
| No hormone, HDAC and no transcription; hormone present, HAT and transcription occurs. |
|
|
Term
| Characterize non-traditional steroid hormone-regulated transcription. |
|
Definition
| Ligand-bound receptor binds to other transcription factors to modulate transcription on cognate DNA elements. |
|
|
Term
| What does SERM stand for and how are they characteristically distinguished from pure receptor agonists or antagonists? |
|
Definition
| Selective estrogen receptor modulator; have different effects in different tissues (example: Raloxifene promotes binding of RRE, rather than typical ERE). |
|
|
Term
| How is nitric oxide generated from arginine? |
|
Definition
| With oxygen and nitric oxide synthase, converts to citrulline. |
|
|
Term
| Where in the cell are guanylyl cyclase receptors found and what activates them? |
|
Definition
| Cytoplasmic enzyme activated by nitric oxide that freely diffuses into the cell; single TM Rc activated by atrial natiuretic peptide. |
|
|
Term
| What is the direct action of guanylyl cyclase? |
|
Definition
|
|
Term
| What might generation of cGMP via guanylyl cyclase activate? |
|
Definition
| cGMP-dependent protein kinase (PKG), cGMP-dependent phosphodiesterase (PDE) |
|
|
Term
| How does sildenafil target the NO/cBMP signaling pathway to treat ED? |
|
Definition
| Cavernous nerve/endothelials release NO to increase guanylyl cyclase generation of cGMP from GTP. Sildenafil (viagra) inhibits PDE while PKG decreases [Ca], leading to smooth muscle relaxation and arterial dilation. |
|
|
Term
| Where is atrial natiuretic peptide released and what does it do? |
|
Definition
| Released by atrial cardiac myocytes in response to atrial stretch and other factors indicating hypervolemia, exercise, or caloric restriction; acts to decrease blood pressure by relaxing smooth muscle and decreasing Na resorption. |
|
|
Term
| Briefly characterize the catalytic cascade present in vertebrate rods. |
|
Definition
| Light-induced rhodopsin molecule activates G protein transducin, phosphodiesterase activated to hydrolyze cGMP, Na channels close and hyperpolarize membrane. |
|
|
Term
| Characterize GTP-binding and the GTPase cycle in G-protein activation. |
|
Definition
| Inactive Gprotein binds activated receptor; GDP/GTP exchange; alpha-subunit acts on receptor until GTP hydrolyzed to GDP. |
|
|
Term
| In what tissues does cholesterol biosynthesis typically occur? |
|
Definition
| Liver, intestine, adrenal cortex, and reproductive tissues |
|
|
Term
| How is cholesterol transported in the body? |
|
Definition
| In a form of water-miscible lipoproteins. |
|
|
Term
| How is dietary cholesterol transported to the liver and peripheral tissues? |
|
Definition
|
|
Term
| What enzyme is the rate-limiting step in cholesterol biosynthesis? |
|
Definition
|
|
Term
| What effect do insulin, thyroid hormone, glucagon, and glucocorticoids have on cholesterol biosynthesis and what enzyme are they acting upon? |
|
Definition
| Insulin, thyroid hormone upregulate HMG-CoA Reductase activity; Glucagon, glucocorticoids downregulate HMG-CoA Reductase activity. |
|
|
Term
| How are bile salts formed? |
|
Definition
| Bile acids are conjugated with glycine or taurine in peroxisomes and are converted to bile salts at physiological pH. |
|
|
Term
| What is the difference between primary and secondary bile acids? Give examples of each. |
|
Definition
| Primary, produced in liver (cholic, deoxychenocholic); secondary, produced by bacteria in the intestine (deoxycholic, lithocholic). |
|
|
Term
| Secretion of bile acids from the liver into the duodenum is controlled by what gastrointestinal hormone(s)? |
|
Definition
| Hepatocrinin and cholecystokinin |
|
|
Term
| What is the primary function of bile acids in the intestine? |
|
Definition
| Act as detergent, assisting the emulsification of ingested lipids into small globules. |
|
|
Term
| What is atherosclerosis and what is the significance and composition of the atherosclerotic plaque? |
|
Definition
| Chronic disease where plaque accumulates in the wall of blood vessels; cholesterol, cholesterol esters, collagen, proteoglycan, elastin; elasticity of blood vessel walls is decreased and blood clots develop. |
|
|
Term
| Describe the function and composition of chylomicrons. |
|
Definition
| Transport dietary lipids from intestines to liver and peripheral tissue; composed predominantly of triacylglycerol. |
|
|
Term
| How do VLDL, LDL, and HDL differ in function and composition? |
|
Definition
| VLDL transports TG liver>periphery, LDL is final stage VLDL catabolism, HDL transports cholesterol periphery>liver. VLDL mostly TAG, LDL mostly cholesterol, HDL mostly protein. |
|
|
Term
| What is the protein moiety of a lipoprotein called? |
|
Definition
| apolipoprotein or apoprotein |
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Term
| On an electrophoretic shift assay, what is the DESCENDING (top to bottom, - to +) ORDER of lipoproteins on the gel? |
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Definition
| Chylomicron, LDL, VLDL, HDL |
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Term
| What is Apo A (I and II) and where is it made? |
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Definition
| Produced in liver and small intestine; major apolipoprotein of plasma HDL, activates cholesterol-lecithin transferase (LCAT), which esterifies free cholesterol in HDL. |
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Term
| What are the forms of Apo B and what are their functions? |
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Definition
| Hepatic, B-100, essential for VLDL packaging and secretion; Intestinal, B-48, essential for chylomicron packaging and secretion. |
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Term
| What cells assemble chylomicrons? |
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Definition
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Term
| What is the composition, site of production, and function of VLDLs? |
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Definition
| Liver, composed of TG, carries lipids from liver to periphery |
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Term
| What is the function of lipoprotein lipase and where is it found? |
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Definition
| Attached to capillaries in muscle and adipose tissue, hydrolyze triglyceride in VLDL and chylomicrons to liberate free FA for oxidation or storage |
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Term
| What is the function of hepatic lipase and where is it found? |
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Definition
| Attached to hepatocytes, role in remnant lipoprotein uptake, acts as ligand to lipoprotein, hydrolyzes lipoprotein triacylglycerol and phospholipid. |
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Term
| What is the primary function of GPCR-activation of the effector adenylyl cyclase? |
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Definition
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Term
| Upon conversion of ATP to cAMP by GPCR-activated adenylyl cyclase, describe the effect on protein kinase A. |
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Definition
| Inactive PKA, a heterotetramer, binds four cAMP units, which causes the regulatory homodimer to release the now-active catalytic homodimer subunit. |
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Term
| What is the role of protein kinase A in glycogen metabolism and/or regulation? |
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Definition
| PKA catalyzes activation of phosphorylation kinase (which activates glycogen phosphorylase for glycogenolysis) and inactivation of glycogen synthase (which prevents glycogenesis). |
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Term
| How does cholera toxin exert its primary effect? |
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Definition
| Targets alpha-stimulatory subunit of Gprotein by inhibiting GTPase, leading to continuous stimulation of AC (and increased cAMP levels) |
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Term
| How does pertussis toxin exert its primary effect? |
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Definition
| Targets alpha-inhibitory subunit of Gprotein by blocking interaction with receptor, prevent inhibition of AC (and increased cAMP levels) |
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Term
| Give three ways in which the cAMP regulatory system might be downregulated. |
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Definition
| 1)Desensitization of the receptor by phosphorylation by BARK, 2)Decrease cAMP concentration by phosphodiesterase, 3)Dephosphorylation of PK substrates by Phosphatase 1 |
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Term
| In general, PKA and PKC activate these downstream signalling molecules, respectively. |
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Definition
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Term
| Define epithelial tissue. |
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Definition
| Composed primarily of cells, covers or lines the organs (sheet-like epithelium) or performs secretory functions (glandular epithelium). |
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Term
| True or false. All membranous epithelium is avascular. |
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Definition
True, with one exception in the inner ear. |
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Term
| In cross-section, what is the primary distinction between cilia and microvilli? |
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Definition
| Cilia: nine doublets in ring with central doublet; microvilli: nine triplets in ring with central mass. |
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Term
| In terms of the ciliary beat, contrast metachronic and isochronic motion. |
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Definition
| Metachronic: in plane of motion (beat one after another), Isochronic: at right angles to the plane of motion (all beat simultaneously) |
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Term
| How does immotal cilia syndrome arise and what is the initial presentation? |
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Definition
| Defects in dynein arms of the nine doublets, preventing normal function of cilia; abnormal to absent clearning of the ariway leading to lung infection. |
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Term
| What are the three types of occludens cellular attachment sites? Describe their appearance. |
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Definition
| Zonular (branching network of sealing strands), Fascia (discontinuous strips of tight junctions), Macula (spot-style tight junction) |
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Term
| What are the three types of adherens cellular attachment sites and how are they constructed? |
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Definition
| Zonular (belt), fascia (ribbon-like patterns, do not completely encircle), macula (also called desmosomes) |
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Term
| How are occludens cellular attachment sites differentiated from adherens? |
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Definition
| In occludens junctions, the membranes of neighboring cells approximate one another, while adherens are usually more basal, essentially connectiong the actin cytoskeletal elements of neighboring cells with one another. |
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Term
| What proteins are important in occludens junctions? |
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Definition
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Term
| What proteins are important in adherens junctions? |
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Definition
| Cadherins and actin microfilaments |
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Term
| What is Pemphigus vulgaris and how does it present? |
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Definition
| Autoimmune disease with antibodies against desmosomal proteins; skin lesions, blisters, raw sores |
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Term
| What is the difference between desmosomes and hemidesmosomes? |
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Definition
| Desmosomes link two cells together while hemidesmosomes link cells to the ECM using integrins. |
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Term
| What is the difference between exocrine and endocrine glands? |
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Definition
| Exocrine, duct carries secretion to a surface; endocrine, secretion into surrounding tissue fluid/blood vessels |
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Term
| If exocrine glandular epithelial cells secrete a watery, enzyme-rich product, they are said to have a --- secretion. |
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Definition
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Term
| If exocrine glandular epithelial cells secrete a thick, gel-like protective lubricant, they are said to have a --- secretion. |
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Definition
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Term
| True or False. Receptors in RTK and JAK-Stat signaling have inherent enzymatic kinase properties. |
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Definition
| False. JAK-stat kinase-ASSOCIATED receptors do not have inherent kinase abilities and rely on JAK kinase. |
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Term
| True or False. Some SOCS have receptor-inhibition properties in addition to their ability to inhibit JAK kinase. |
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Definition
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Term
| How do SOCS, SHP-1, and PIAS downregulate JAK-Stat regulated pathways? |
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Definition
| SOCS: transcribed inhibitors of receptor or JAK; SHP-1: dephosphorylates activated receptor; PIAS: prevents translocation of activated Stat. |
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Term
| Briefly characterize Delta-notch signaling. |
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Definition
| Direct cell-cell signaling (no back-signaling however), gamma-secretase cleaves intracellular portion from Notched, which travels into nucleus to modulate transcription. |
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Term
| Briefly characterize Hedgehog signaling. |
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Definition
| Sans HH, Patched binds Smoothened, Fused/Coastal2/Ci155 complex bound to microtubule, Ci155 cleaved and Ci75 travels to nucleus to repress transcription. Con HH-Patched binding, Smoothened binds Fused/Coastal 2/Ci155, Ci155 travels to nucleus and acts as TF. |
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Term
| What type of signaling is absolutely required for cartilage and bone development and why? |
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Definition
| Hedgehog; Hedgehog limiting will form limited bone growth field (growth plate). |
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Term
| Briefly characterize Wnt-betaCatenin signaling. |
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Definition
| Sans Wnt, no binding of Frizzled-LRP by Dishevelled/Axin, betaCatenin phosphorylated by GSK-3beta and degraded. Con Wnt,Dishevelled/Axin binds Wnt-LRP, GSK03beta inactive and betaCatenin travels to nucleus to facilitate transcription. |
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Term
| Wnt-betaCatenin signaling may be downregulated by secretion of --- … |
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Definition
| …FRP (a truncated Frizzled analog) to 'bind up' ligand. |
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Term
| How does activation of transcription by NF-kB occur and how is it inhibited? |
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Definition
| Signal (such as IL-1) activates IkB kinase, which phosphorylates (targets for degradation) the IkB subunit, leaving a NF-kB dimer TF complex which travels to the nucleus, where IkB mRNA is transcribed and returns to the cytosol. |
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Term
| Smad 2 and 4 can act as transcriptional inhibitors in… |
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Definition
| …IL-6 dependent signaling. |
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Term
| How might crosstalk occur between the GPCR and ERK signaling pathways? |
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Definition
| Receptor inactivation by GRK (G receptor kinase), betaArrestin assocation with receptor acts as scaffold for Raf, MEK, and ERK. |
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Term
| How do caspases get their name? |
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Definition
| Cysteine (active site) + Aspartic acid (substrate) + Proteases |
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Term
| Characterize the three groups of caspases. |
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Definition
| I: 1,4,5 (cytokine maturation, little to do with cell death); II: 2,3,7 (principal killer proteins); III: 6,8,9,10 (upstream of II, initiators of group II) |
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Term
| What effect does released TNF during infection have on a tumor? |
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Definition
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Term
| How does necrosis primarily differ from apoptosis? |
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Definition
| Necrosis due to physio/chem/mechanical damage, leads to inflammation; apoptosis due to programmed death, 'blebbing' leads to no inflammation. |
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Term
| How might cellular apoptosis be initiated by Fas ligand or TNF? |
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Definition
| Receptor activation, binding of adaptor protein, binding of caspase 8, autocleavage into active caspase 8, activation of caspase cascade. |
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Term
| How does cytochrome C promote activation of the caspase cascade via caspase 9? |
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Definition
| Release of cytochrome C by mitochondria activates Apaf 1 (the apoptosome), which cleave pro-caspase 9 to its active form, activating the caspase cascade. |
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Term
| What is the primary effect of Bcl-2 on mitchondria? |
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Definition
| Prevents release of cytochrome C. |
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Term
| What is the primary effect of Bad/Bid on mitochondria? |
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Definition
| Normally inactive, found in cytoplasm; when activated by dephosphorylation, moves to mitochondria and causes cytochrome c release. |
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Term
| How might PI-3 kinase (via RTK or GPCR activation) exhibit anti-apoptotic properties? |
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Definition
| Activation via RTK or GPCR: PIP2>PIP3, Akt activated and phosphorylates Bad (inhibits Bad's pro-apoptotic move out of cytoplasm) and caspase 9 (inactivates) and blocks FOXO transcription. |
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