Term
| Product removal would make delta G _____ and drive the reaction forward. |
|
Definition
|
|
Term
|
Definition
| ΔGo + RT x ln (*products+/*reactants+) |
|
|
Term
| Describe end product feedback regulation of a metabolic pathway. |
|
Definition
| Product of the reaction competes with the substrate for the active site of the enzyme. Biosynthetic pathways inhibited by high concentrations of end product. Switches off the pathway when there is enough product in the cell. Very specific. Genetically determined (allosteric effector). |
|
|
Term
| 4.1 What is the importance of the rate-limiting step in a biochemical pathway? Where is it usually found? |
|
Definition
| It has to catalyze the rate limiting step. The rate limiting step is the slowest step, usually found as the first committed step in a pathway (usually THE first step, or near the beginning). |
|
|
Term
| 4.2 What does the term 'committed step' imply regarding reversibility? |
|
Definition
| Irreversible. Once the substrate comes this far, it is committed to going thru with the rest of the reaction. Regulation of this step ensures a buildup of substrates and not metabolic intermediates (with possible toxic effects). |
|
|
Term
| 2.1 What is a reducing sugar? Is sucrose a reducing sugar? Why not? |
|
Definition
| Carbonyl group of monosaccharides (the one attached to the O of the ring and an OH) has reducing properties. Reducing properties are lost when carbonyl carbon forms glycosidic bond. Reducing sugars include glucose, fructose, galactose, glyceraldehydes, lactose, arabinose, and maltose. Sucrose is NOT a reducing sugar because both anomeric carbons participate in glycosidic bond. The other disaccharides have a reducing end and a nonreducing end. |
|
|
Term
| Give another name for a glycosidic bond |
|
Definition
|
|
Term
| 3.1 What effect does a glycosidic bond have on the ring structure of a monosaccharide? |
|
Definition
| A glycosidic bond involves the anomeric carbon of one of the participating monosaccharides (carbon 1 in aldoses and carbon 2 in ketoses, usually). Once the bond is formed, mutarotation (the occasional opening and reclosure of the ring from an αβ isomer or vice versa) is no longer possible, and the bond is locked in its conformation. |
|
|
Term
| 3.3 What are the three digestible disaccharides found in the diet of humans? |
|
Definition
| Maltose, sucrose, and lactose |
|
|
Term
| 3.4 What is an indigestible polysaccharide found in the diet of humans that contains only glucose monomers? Why can't we digest it? |
|
Definition
| Cellulose. We do not have the enzyme cellulase to digest it. Also, it has β(1,4) glycosydic bonds instead of α (which are in starch and glycogen). |
|
|
Term
| 3.5 What's different about the glycosidic bond in sucrose? |
|
Definition
| Both anomeric carbons participate in the glycosidic bond. (aB-1,2 bond) |
|
|
Term
| Explain how anomers are different from each other. |
|
Definition
| When the ring structure forms, the carbon becomes asymmetrical. There are 2 possible isomers, β (OH on top) and α (H on top). They interconvert spontaneously. |
|
|
Term
| 1. Give the characteristics and the role of the GLUT glucose transporters. |
|
Definition
- Passive – requires no ATP
- Family of 8 uniport (one direction) membrane proteins
- GLUT2: high Km, high Vmax; liver and beta cells in pancreas islets (endocrine pancreas)
o Principal transporter for glucose between liver and blood
o Resists letting glucose in, very reluctant transporter
o Resistant unless there’s a lot of sugar in the blood
- GLUT4: Insulin responsive; muscle and adipose
o Responsible for insulin regulated glucose disposal
o In absence of insulin, most GLUT4 transporters are in membranes of intracellular vesicles
o Activation of insulin receptor triggers fusion of these vesicles with plasma membrane
o Muscle and adipose tissue take up glucose after carb-rich meal when insulin level is high
o They do not take up glucose during fasting when insulin is low |
|
|
Term
| Which Glut Transporter is insulin responsive? |
|
Definition
|
|
Term
| Where are the GLUT 4 Transporters found? |
|
Definition
|
|
Term
| GLUT 2 has a ____ Km and ____ Vmax |
|
Definition
|
|
Term
| Where are GLUT 2 Transporters found? |
|
Definition
| Liver and Beta Cells in pacrease inlets of the Pancreas |
|
|
Term
| GLUT glucose transporters is a family of _____ |
|
Definition
| eight uniport (one-direction) membrane proteins |
|
|
Term
| GLUT glucose transporters, do they require ATP? |
|
Definition
|
|
Term
| GLUT _____ is Responsible for insulin regulated glucose disposal |
|
Definition
|
|
Term
| Muscle and adipose tissue take up glucose after carb-rich meal when ______. |
|
Definition
|
|
Term
| Muscle and adipose tissue take up glucose when? |
|
Definition
|
|
Term
| Principal transporter for glucose between liver and blood? |
|
Definition
|
|
Term
| GLUT2 is resitant unless _____ |
|
Definition
| there’s a lot of sugar in the blood (High Km and Vmax) |
|
|
Term
|
Definition
|
|
Term
| Glucokinase substrate(s)? |
|
Definition
|
|
Term
| Is Glucokinase inhibited by G-6-P |
|
Definition
|
|
Term
| Glucokinase is found _______ |
|
Definition
| in liver and B cells of pancreas |
|
|
Term
| Glucokinase matches with GLUT_ |
|
Definition
|
|
Term
| Glucokinase is induced by ______. |
|
Definition
|
|
Term
| Who has a higher Km, Glucokinase or HexoKinase? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| galactose, glucose, and fructose substrates |
|
|
Term
| Is Hexokinase inhibited by G-6-P? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| Glucose phosphorylated by ATP to produce G-6-P |
|
|
Term
| Hexokinase is ____ distributed. |
|
Definition
|
|
Term
| Hexokinase matches with GLUT_. |
|
Definition
|
|
Term
| In what organ is glucokinase located? |
|
Definition
| liver and B cells of pancreas |
|
|
Term
| How is glucokinase adapted to the function of the liver? |
|
Definition
| Reaction rate varies with glucose level. Glucose is higher in portal vein than systemic blood after a carb meal. Glucokinase is inhibited by CoA thioesters of long chain fatty acids, which are most abundant during fasting (when liver metabolizes large amounts of fatty acids from adipose tissue). |
|
|
Term
| Is glucokinase regulated by G6P in addition to hexokinase? |
|
Definition
|
|
Term
| _____ adapts liver for rapid uptake of excess glucose |
|
Definition
|
|
Term
| Reaction Rate curve is ____ shaped for hexokinase and ____ shaped for glucokinase. |
|
Definition
hyperbolic (like myoglobin)
glucokinase (sigmodial) |
|
|
Term
| Who has a lower affinity for glu, glucokinase or hexokinase? |
|
Definition
|
|
Term
| Cellular location of the glycolytic pathway? |
|
Definition
|
|
Term
| 4.1 How is glucose trapped inside the cell? |
|
Definition
| The first step in glucose metabolism always uses hexokinase to turn glucose into Glucose-6-Phosphate, which cannot leave the cell on a membrane carrier like glucose can. (Phosphorylated intermediates in general do not cross plasma membrane.) |
|
|
Term
| How many of the enzymes that convert glucose to G3P (Glyceraldhyde-3-P) are kinases? |
|
Definition
| 2 Hexokinase & Phosphofructokinase |
|
|
Term
| Which reaction splits the 6-carbon skeleton into two 3-carbon skeletons in Glycolysis? |
|
Definition
| Reaction 4. Fructose 1,6 bisphosphate -> dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. Catalyzed by enzyme aldolase. |
|
|
Term
| How does dihydroxyacetone-PO4 get back into the glycolytic pathway? |
|
Definition
| Triose phosphate isomerase converts it into glyceraldehyde-3-phosphate |
|
|
Term
| 5.1 Where is NADH produced in glycolysis? |
|
Definition
| Reaction 6. Glyceraldehyde-3-phosphate <-> 1,3-bisphosphoglycerate via glyceraldehyde-3-phosphate dehydrogenase. Couples exergonic oxidation of aldehyde group with endergonic formation of energy-rich mixed anhydride bond. Phosphate group from inorganic phosphate, NOT ATP. Also NAD+ -> NADH, H+. |
|
|
Term
| 5.2 Which steps produce ATP in glycolysis? |
|
Definition
Reaction 7 and Reaction 10.
1,3 BPG to 3-phosphoglycerate via phosphoglycerate kinase
and
PEP to Pyruvate via pyruvate kinase |
|
|
Term
| So, what other intermediate besides glucose lacks a PO4 in glycolysis? |
|
Definition
|
|
Term
| Glycolysis – The first five reactions _____ |
|
Definition
|
|
Term
| First reaction of glycolysis results in glucose ______ |
|
Definition
|
|
Term
| Phosphofructokinase is part of the _____ half of steps in glycolysis and acts as a ______ |
|
Definition
1st
regulatory point for glycolysis |
|
|
Term
| Glyceraldehyde 3-PO4 (G3P) is a _______. |
|
Definition
|
|
Term
| 1st place energy is consumed in glycolysis? |
|
Definition
|
|
Term
| 2nd place energy is consumed in glycolysis? |
|
Definition
Reaction 3.
Phosphofructokinase (ATP to ADP) |
|
|
Term
| The Last Five Reactions of Glycolysis ______. |
|
Definition
|
|
Term
| The Last Five Reactions of Glycolysis produce energy in form of _______. |
|
Definition
| NADH (reaction 6) & ATP (reaction 7 and 10) |
|
|
Term
| oxidative phosphorylation happens in the ____ through ______? |
|
Definition
|
|
Term
| phosphofructokinase catalyzes? |
|
Definition
3rd reaction of glycolysis, the second energy consuming step
F6P to F-1,6-BP (Uses ATP to ADP) |
|
|
Term
| long term control of PFK (Phosphofructokinase)? |
|
Definition
| enzyme amounts (new synthesis) |
|
|
Term
| Short term control of PFK (Phosphofructokinase)? |
|
Definition
| allosteric regulation (e.g. after a meal, during exercise) |
|
|
Term
| Stimulators of PFK (Phosphofructokinase)? |
|
Definition
|
|
Term
| Inhibitors of PFK (Phosphofructokinase)? |
|
Definition
| ATP (signals adequate energy), citrate (signals that TCA cycle is full), glucagon (opp effect of insulin), low pH, epinephrine |
|
|
Term
| Adenylate kinase catalyzes ______ |
|
Definition
| 2ADP <-> ATP + AMP in desperate situations |
|
|
Term
| In liver, PFK (Phosphofructokinase) is regulated by ______ |
|
Definition
|
|
Term
| In muscle, PFK (Phosphofructokinase) is regulated by ______ |
|
Definition
| insulin/epinephrine ratio |
|
|
Term
| epinephrine effect on PFK (Phosphofructokinase)? |
|
Definition
|
|
Term
| Hormones regulators of PFK (Phosphofructokinase)? |
|
Definition
| Hormones: Insulin and glucagon |
|
|
Term
| Allosteric effectors of PFK (Phosphofructokinase)? |
|
Definition
| Allosteric effectors: Citrate (End product of TCA)inhibits, AMP stimulates, ADP stimulates, ATP inhibits |
|
|
Term
| Which way would ATP and citrate move the sigmoid shaped (S vs. V) curve for PFK? |
|
Definition
| ATP and citrate: shift curve to the right (increase Km).... inhibitors |
|
|
Term
| Which way would AMP and ADP move the sigmoid shaped (S vs. V) curve for PFK? |
|
Definition
| AMP and ADP: shift curve to the left (decrease Km).... stimulators |
|
|
Term
| Name the enzyme that makes anaerobic glycolysis possible by using up the NADH that accumulates. |
|
Definition
|
|
Term
| Why would NADH accumulate? |
|
Definition
| Glycolysis produces NADH, but in anaerobic conditions, there is no oxygen to regenerate the NADH -> NAD+. Thus NADH would accumulate, and glycolysis would stop. To solve this, the hydrogen of NADH is transferred to the keto group of pyruvate, forming lactate. This reaction is catalyzed by LDH. |
|
|
Term
|
Definition
| Pyruvate to Lactate, which takes a NADH and turns it into NAD+ to be used back in step 6 of glycolysis to produce NADH |
|
|
Term
| Why doesn't hypoxia just shut down glycolysis instead of speeding it up? |
|
Definition
| Shortage of ATP stimulates glycolysis at the level of PFK. Pyruvate is formed but can’t be oxidized by mitochondria, so is turned into lactate by LDH. Accumulating lactic acid acidifies tissue and causes cell death. |
|
|
Term
| Compare lactate formation in erythrocytes, skeletal muscle, and hypoxia. |
|
Definition
Erythrocytes: no mitochondria, continual lactate production, lactate converted to glucose by liver
Skeletal muscle: fast twitch – few mitochondria, high LDH. Slow twitch – many mitochondria, low LDH.
Hypoxia: Low oxygen so NADH cannot be oxidized by mitochondria -> inc. NADH -> inc. lactate production |
|
|
Term
| Lactic acidosis is _______ |
|
Definition
| the overproduction or under utilization of lactic acid |
|
|
Term
| Most common cause of Lactic acidosis is _______ |
|
Definition
| impairment of oxidative metabolism by respiratory failure, insufficient oxygen transport, or direct inhibition of oxidation phosphorylation |
|
|
Term
| _____ regenerates NAD+ for glycolysis |
|
Definition
|
|
Term
| Lactate is a metabolic _____. |
|
Definition
|
|
Term
| ____ is the only enzyme that recognizes lactate |
|
Definition
|
|
Term
| Erythrocytes (RBC’s) undergo continuous production of _______ |
|
Definition
|
|
Term
| Lactate is converted to glucose by _____. |
|
Definition
|
|
Term
| Skeletal muscle: Fast twitch: ____ mitochondria, ____ LDH |
|
Definition
|
|
Term
| Skeletal muscle: Slow twitch: ____ mitochondria, ___ LDH |
|
Definition
|
|
Term
| 90% arterial blockage leads to ____ |
|
Definition
|
|
Term
| Causes of Lactic Acidosis: ______ |
|
Definition
| Increased NADH & Increased pyruvate |
|
|
Term
| ______ leads to a reversal of the NADH shuttle |
|
Definition
|
|
Term
| Increased NADH sources, such as _____, can lead to an increase in NADH and therefore lactic acidosis. |
|
Definition
|
|
Term
| Increased pyruvate levels that lead to Lactic Acidosis can stem from ________. |
|
Definition
| Pyruvate dehydrogenase deficiency |
|
|
Term
| _____ deficiency can cause pyruvate to increase and lead to lactic acidosis? |
|
Definition
|
|
Term
| Describe the effect of a genetic pyruvate kinase deficiency on anaerobic glycolysis |
|
Definition
Does last step of glycolysis
PEP + ADP + Pi > Pyruvate + ATP
Partial block of anaerobic glycolysis
PEP would not be converted into pyruvate and 2 ATPs would not be formed. |
|
|
Term
|
Definition
| enolase (reaction 9) which converts 2-phosphoglycerate to PEP |
|
|
Term
| What would be the similarity between a pyruvate kinase deficiency and fluoride inhibition? How would they be different? |
|
Definition
- Pyruvate kinase deficiency prevents reaction 10 of glycolysis, PEP pyruvate
- Fluoride inhibits enolase (reaction 9) which converts 2-phosphoglycerate to PEP
- Either way, the formation of 2 ATPs would be lost |
|
|
Term
| What type of anemia is seen in people with pyruvate kinase deficiency? Why? |
|
Definition
| hemolytic anemia, because RBC’s are the most vulnerable – they have no other way to produce ATP |
|
|
Term
| hemolytic anemia results from ____ |
|
Definition
| pyruvate kinase deficiency |
|
|
Term
| _____ is most vulnerable to pyruvate kinase deficiency |
|
Definition
|
|
Term
| Pyruvate kinase deficiency results in a ____ of glycolysis. |
|
Definition
|
|
Term
| Enolase inhibition by _______ |
|
Definition
|
|
Term
|
Definition
| Catalyzes 9th step in glycolysis PEP to Pyruvate |
|
|
Term
| What inorganic molecule does arsenate mimic? |
|
Definition
|
|
Term
| Does arsenate block glycolysis? |
|
Definition
| No, still makes 3-phosphoglycerate |
|
|
Term
| Would arsenate prevent anaerobic glycolysis? |
|
Definition
| No, but ATP would not be formed (by step 7, which turns 1,3-bisphosphoglycerate into 3-phosphoglycerate via phosphoglycerate kinase, which usually would have given ADP -> ATP). |
|
|
Term
| TCA cycle overall reaction:_____ |
|
Definition
| TCA cycle: Acetyl-CoA + GDP + Pi + 3 NAD+ +Q ------> 2 CO2 + CoA + GTP + 3 NADH + QH2 |
|
|
Term
| Overall reaction pyruvate to acetyl-CoA and NADH: |
|
Definition
| Pyruvate + NAD+ + CoA-SH --> Acetyl CoA + NADH + CO2. Catalyzed by pyruvate dehydrogenase |
|
|
Term
| Pyruvate DH produces _____. |
|
Definition
| CO2 byproduct and forms HE-TPP as its product |
|
|
Term
| Pyruvate dehydrogenase complex includes: ______ |
|
Definition
Pyruvate dehydrogenase complex includes:
- Pyruvate dehydrogenase component (E1): contains thiamine pyrophosphate as prosthetic group.
- Dihydrolipoyl transacetylase component (E2): contains lipoic acid covalently bound to lysine side chain
- Dihydrolipoyl dehydrogenase component (E3): flavoprotein containing FAD.
The reaction also requires NAD+ and CoA cosubstrates. |
|
|
Term
| ____ turns HE-TPP into Acetyl CoA |
|
Definition
|
|
Term
| Pyruvate is Oxidized to _____ |
|
Definition
|
|
Term
| Pyruvate is Oxidized to Acetyl-coA In The ______ |
|
Definition
|
|
Term
| Lipoate (lipoic acid) interacts with all three enzymes of the _____ complex. |
|
Definition
|
|
Term
| Lipoate (lipoic acid) interacts with all three enzymes of the pyruvate dehydrogenase complex. What is the enzymatic step involving lipoate at each interaction? |
|
Definition
| Lipoic acid participates as a redox system and carrier of the acetyl group |
|
|
Term
What is the original vitamin for each of the cofactors?
Pantothenic acid:
Niacin:
Riboflavin:
Thiamine (B1): |
|
Definition
- Pantothenic acid: CoA
Niacin: NAD
Riboflavin: FAD
Thiamine (B1): Thiamine pyrophosphate (TPP) |
|
|
Term
| Where is pyruvate dehydrogenase complex located in the cell? |
|
Definition
|
|
Term
|
Definition
Lactate: dehydrogenation
Alanine: transamination
PEP: Pyruvate kinase reaction |
|
|
Term
|
Definition
Pyruvate oxidation
Ketone body oxidation |
|
|
Term
| Thiamine (B1) deficiency causes ______ disorder, which is characterized by ______ |
|
Definition
| beriberi: paralytic, nervous, or cardiac symptoms |
|
|
Term
| Causes of Thiamine (B1) deficiency: _____ |
|
Definition
| absence in diet, alcoholism |
|
|
Term
| Thiamine (B1) deficiency produces ______ |
|
Definition
|
|
Term
| Thiamine (B1) deficiency causes elevated levels of _____ after a high carb meal. |
|
Definition
| Causes elevated blood levels of pyruvate, lactate, and alanine after a high carb meal. |
|
|
Term
| What amino acid can pyruvate be converted to and vice versa? |
|
Definition
|
|
Term
| What amino acid can OAA be converted to and vice versa? |
|
Definition
|
|
Term
| In addition to aspartate OAA can be transformed into _____ |
|
Definition
|
|
Term
| Thiamine deficiency causes Pyruvate to accumulates because its major reaction is blocked, and it is either reduced to ____ or transaminated to _____. |
|
Definition
|
|
Term
| Three different causes of pyruvate dehydrogenase impairment: ______ |
|
Definition
Thiamine deficiency
Inherited partial deficiencies of pyruvate dehydrogenase (Genetic)
Arsenite poisoning (nerve gas) |
|
|
Term
| Inherited partial deficiencies of pyruvate dehydrogenase causes ____ and leads to ____ dysfunction. |
|
Definition
lactic acidosis
central nervous system dysfunction |
|
|
Term
| With Inherited partial deficiencies of pyruvate dehydrogenase, the brain suffers the most, because _____. |
|
Definition
| because pyruvate dehydrogenase needed for carb oxidation |
|
|
Term
| With Arsenite poisoning, Arsenite ties up _____. |
|
Definition
|
|
Term
|
Definition
•
Pyruvate oxidation
•
Fat oxidation
•
Amino acid degradation
•
Ketone body oxidation |
|
|
Term
| Arsenite poisoning causes _____ |
|
Definition
|
|
Term
| ____ Regulation Of Pyruvate Dehydrogenase |
|
Definition
|
|
Term
| can hypoxia cause a buildup of lactate? |
|
Definition
|
|
Term
| Hypoxia leads to ___ NAD+/NADH ratios, because ______. |
|
Definition
decreased NAD+/NADH ratios (higher NADH)
NADH cannot be oxidized by oxygen |
|
|
Term
| Hypoxia leads to elevated NADH levels and therefore need to ______ to reform NAD+ for continued glycolysis and ATP production. |
|
Definition
|
|
Term
| How can hypoxia cause a buildup of lactate? |
|
Definition
| Hypoxia leads to decreased NAD+/NADH ratios (higher NADH) because NADH can’t be oxidized by oxygen. Needs to form lactate to reform NAD+ for continued glycolysis and ATP production. Also, increased AMP/ATP ratio (shortage of ATP) stimulates glycolysis at the level of PFK. Pyruvate is formed but can’t be oxidized and must be changed into lactate. |
|
|
Term
| increased AMP/ATP ratio (shortage of ATP) stimulates glycolysis at the level of ____ enzyme. |
|
Definition
|
|
Term
| PDH (Pyruvate DH) is regulated by? |
|
Definition
|
|
Term
| PDH Kinase: ____ PDH by phosphorylation |
|
Definition
|
|
Term
| PDH Kinase, which inactivates PDH by phosphorylation is stimulated by ______ and Decreased by ______. |
|
Definition
Stimulated by NADH, Acetyl-CoA
pyruvate, Ca2+ |
|
|
Term
| PDH phosphatase: _____ PDH by dephosphorylation |
|
Definition
|
|
Term
| PDH phosphatase, which reactivates PDH by dephosphorylation is is stimulated by ______. |
|
Definition
|
|
Term
| What cofactors stimulate the activity of the PDH kinase? |
|
Definition
|
|
Term
| What cofactors inhibit the activity of the PDH kinase? |
|
Definition
|
|
Term
| What hormone affects the phosphorylation of PDH? |
|
Definition
| Insulin stimulates PDH Phosphatase in order to dephosphorylate PDH in order to activate it to form Acetyl CoA |
|
|
Term
| cellular location of the TCA cycle. |
|
Definition
|
|
Term
| TCA cycle located in mitochondrial matrix adjacent to ______. |
|
Definition
|
|
Term
| OAA + Acetyl CoA forms ______ (_C) |
|
Definition
|
|
Term
| TCA Cycle forms citrate (6C) and then remove CO2 to produce _____(4C) during the _____ steps of the TCA Cycle. |
|
Definition
|
|
Term
| How many NADH are produced from one molecule of pyruvate when it is metabolized all the way to CO2 and water? |
|
Definition
| 4 NADH (3 from TCA and 1 from pyruvate ---> acetyl-CoA) |
|
|
Term
| How many ATP (GTP) are produced from one molecule of pyruvate when it is metabolized all the way to CO2 and water? |
|
Definition
|
|
Term
| Aconitase enzyme function? |
|
Definition
| Converts Citrate into Isocitrate reversibly. |
|
|
Term
| Aconitase can be inhibited by ______? |
|
Definition
| Fluoroacetate inhibition (makes fluorocitrate; inhibits aconitase) |
|
|
Term
| First committed step of TCA cycle is ______ |
|
Definition
| Isocitrate to alpha ketoglutarate by Isocitrate DH which produces CO2 and NADH |
|
|
Term
| Last Four TCA Cycle Reactions involve the conversion of ____ back into _____. |
|
Definition
| Succinate (4C) back into OAA (4C) |
|
|
Term
| _____ is produced in the last 4 steps of TCA cycle. |
|
Definition
|
|
Term
| Pyruvate Dehydrogenase vs. Alpha-Ketoglutarate Dehydrogenase: Both act on an _____ substrate |
|
Definition
|
|
Term
| Pyruvate is a alpha _____ |
|
Definition
|
|
Term
| Pyruvate Dehydrogenase vs. Alpha-Ketoglutarate Dehydrogenase: Both produce a _____ |
|
Definition
|
|
Term
| Pyruvate Dehydrogenase vs. Alpha-Ketoglutarate Dehydrogenase Both are _____ complexes. |
|
Definition
|
|
Term
| Pyruvate Dehydrogenase vs. Alpha-Ketoglutarate Dehydrogenase: Both exist in the _____. |
|
Definition
|
|
Term
| Pyruvate Dehydrogenase vs. Alpha-Ketoglutarate Dehydrogenase, which is regulated by covalent modification? |
|
Definition
|
|
Term
| Last Four TCA Cycle Reactions involve the conversion of ____ back into _____. |
|
Definition
| Succinate (4C) back into OAA (4C) |
|
|
Term
| What enzyme do pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase share in common? |
|
Definition
| E3 (dihydrolipoyl dehydrogenase). |
|
|
Term
| What products do pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase produce in common? |
|
Definition
|
|
Term
| Alpha-ketoglutarate DH produces ______. |
|
Definition
|
|
Term
| Pyruvate DH produces _____. |
|
Definition
|
|
Term
| Citrate synthase catalyzes? |
|
Definition
| Joining of Acetyl CoA and OAA to form Citrate |
|
|
Term
| Citrate synthase is inhibited by: _______ |
|
Definition
| ATP, NADH, succinyl-CoA, and citrate (competes with oxaloacetate for active site) |
|
|
Term
| Citrate synthase is Stimulated by _____. |
|
Definition
|
|
Term
| Isocitrate dehydrogenase is inhibited by ______. |
|
Definition
|
|
Term
| When isocitrate dehyrogenase is inhibited, ____ accumulates and can leave the mitochondrion to act as allosteric effector |
|
Definition
|
|
Term
| Isocitrate dehydrogenase Stimulated by ____ |
|
Definition
|
|
Term
| Primary regulation point of TCA = ______. |
|
Definition
|
|
Term
| Primary regulation point = isocitrate dehydrogenase. Makes _____ pile up and make fat. |
|
Definition
|
|
Term
| Alpha ketoglutarate DH inhibited by _______ |
|
Definition
| its own products (succinyl-CoA and NADH) and by high energy charge (ATP or GTP). NOT phosphorylation/dephosphorylation |
|
|
Term
| Aconitase: inhibited by _______. |
|
Definition
|
|
Term
| List three pairs of amino acids and their corresponding alpha-keto acids that are produced by transamination: ______. |
|
Definition
Alanine- Pyruvate
Glutamate- α – ketoglutarate
Aspartate- Oxaloacetate |
|
|
Term
| Name the TCA cycle intermediates that can also be derived from amino acids. |
|
Definition
α – ketoglutarate (Glutamate)
Oxaloacetate (Aspartate)
Fumarate (Amino Acids)
Succinyl-CoA (Amino acids) |
|
|
Term
| Give the TCA cycle intermediates that can be converted into precursors for other metabolic products. |
|
Definition
| Citrate: precursor for acetyl-CoA during fatty acid synthesis Succinyl-CoA: precursor for heme synthesis Oxaloacetate: precursor for glucose synthesis (gluconeogenesis) |
|
|
Term
| Which intermediate of the TCA carries two carbon units to the cytoplasm for fat synthesis? |
|
Definition
|
|
Term
| Which intermediate is a precursor for heme synthesis? |
|
Definition
|
|
Term
| Which precursor serves as a precursor for glucose synthesis (gluconeogenesis)? |
|
Definition
|
|
Term
| Which intermediate can be transaminated to form glutamate? |
|
Definition
|
|
Term
| Which intermediate can be transaminated to form aspartate? |
|
Definition
|
|
Term
| Aminotransferases transfer the amino nitrogen from an amino acid to an alpha ketoacid, this requires ______ |
|
Definition
|
|
Term
| TCA Cycle Intermediates that serve As Precursors? |
|
Definition
Citrate
Succinyl-CoA
Oxaloacetate |
|
|
Term
| Thiamine binds _____ and releases _____. |
|
Definition
| Pyruvate and release CO2 & Acetyl CoA |
|
|
Term
| Biotin binds _____ and releases _____. |
|
Definition
|
|
Term
| Pyruvate carboxylase binds ___ then transfers it to ____ |
|
Definition
|
|
Term
| Pyruvate Carboxylase produces oxaloacetate; which is also precursor for ______. |
|
Definition
|
|
Term
| Increased Oxaloacetate created by Pyruvate Carboxylase Allows More ____ Capacity |
|
Definition
|
|
Term
| Which intermediate can be replenished by an anaplerotic reaction? |
|
Definition
| Oxaloacetate from pyruvate by pyruvate carboxylase. |
|
|
Term
| What the heck is an anaplerotic reaction? |
|
Definition
| Reactions that regenerate TCA cycle intermediates that have been removed for biosynthesis. |
|
|
Term
| vitamin cofactor for pyruvate carboxylase is ______. |
|
Definition
|
|
Term
| Conversion of Pyruvate to OAA by pyruvate carboxylase is a ____ dependent reaction. |
|
Definition
|
|
Term
| Conversion of Pyruvate to OAA by pyruvate carboxylase is a ATP dependent reaction that uses the energy to ______. |
|
Definition
| Attach CO2 to Biotin so that it can transfer the CO2 to Pyruvate to form OAA |
|
|
Term
| Respiration generates _____ & _____ from O2 and fuel. |
|
Definition
|
|
Term
| Cytochromes – contain ____ |
|
Definition
|
|
Term
| _____ has a isoprene tail (fat soluble) |
|
Definition
|
|
Term
| cytochrome oxidase has a ____ metal cofactor. |
|
Definition
|
|
Term
| Most components of the ETC are derived from? |
|
Definition
|
|
Term
| Flavoproteins accept electrons from ____ and donate to _____. |
|
Definition
|
|
Term
| Flavoproteins generate ______ |
|
Definition
| Free Radical intermediates |
|
|
Term
| Iron-Sulfur Proteins are also called _____ |
|
Definition
|
|
Term
| Iron-Sulfur Proteins acts as ______. |
|
Definition
| redox electron carrier (acceptor/donor) |
|
|
Term
|
Definition
|
|
Term
| Ubiquinone contains a _____, composed of ______ |
|
Definition
isoprene tail
10 isoprene units |
|
|
Term
| Ubiquinone – aka Coenzyme Q10 is ____ soluble. |
|
Definition
|
|
Term
| Ubiquinone – aka Coenzyme Q10 can generate ______. |
|
Definition
| Free Radical Intermediates |
|
|
Term
| Cytochromes are _______ proteins. |
|
Definition
| Integral membrane proteins |
|
|
Term
| Cytochromes contain ______. |
|
Definition
|
|
Term
| In Cytochromes iron alternates between ______. |
|
Definition
|
|
Term
| In Cytochromes iron alternates between Fe+2 and Fe+3, just as with _____ proteins. |
|
Definition
|
|
Term
| Cytochrome oxidase also uses ______ |
|
Definition
|
|
Term
| Cytochromes are bound to two amino acids to prevent _____ |
|
Definition
|
|
Term
| Riboflavin cofactors _____. |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Give the two forms of iron in the electron transport chain (ETC). |
|
Definition
|
|
Term
| Iron-sulfur proteins (aka non-heme iron proteins) Acts as ______. |
|
Definition
|
|
Term
| Iron-sulfur proteins (aka non-heme iron proteins) Transfer electrons by switching between _____ and ______. |
|
Definition
| ferrous (Fe2+) and ferric (Fe3+) states |
|
|
Term
| Cytochromes are ______ proteins |
|
Definition
|
|
Term
| Cytochromes switch between ____ and ____ states |
|
Definition
| ferrous (Fe2+) and ferric (Fe3+) states |
|
|
Term
| Cytochromes are integral membrane proteins, except ______ |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Ubiquinone (Coenzyme Q) is the ____ form |
|
Definition
|
|
Term
| Ubiquinone (Coenzyme Q) can generate |
|
Definition
|
|
Term
| Ubiquinone (Coenzyme Q) carries ____ |
|
Definition
|
|
Term
| Ubiquinol (Coenzyme QH2) is the ____ form. |
|
Definition
|
|
Term
| What are the solubility properties of ubiquinone |
|
Definition
|
|
Term
| Ubiquinone (Coenzyme Q) transfers electrons from _____ to _____ |
|
Definition
| Complex I (NADH-Q reductase) to Complex III (Cytochrome reductase) |
|
|
Term
| NADH-Q reductase function? |
|
Definition
| Reduces CoQ (Ubiquinone ) |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Complex I: NADH-Q reductase contains _______ |
|
Definition
FMN and several iron-sulfur centers
No cytochromes |
|
|
Term
| Complex II: Succinate-Q reductase contains _______ |
|
Definition
Electrons transferred directly to ubiquinone
No cytochromes |
|
|
Term
| Complex III: Cytochrome reductase contains _______ |
|
Definition
Cytochrome b (iron-sulfur protein)
Cytochrome c1 |
|
|
Term
| Complex IV: Cytochrome oxidase contains _______ |
|
Definition
| 2 heme a groups (cytochromes a and a3) each near a copper ion |
|
|
Term
| Which cytochrome is soluble and not bound in the mitochondrial membrane? |
|
Definition
| Cytochrome c, water soluble (soluble in intermembrane space) |
|
|
Term
| What do the cytochromes have in common with myoglobin? |
|
Definition
| Heme group, integral membrane proteins |
|
|
Term
| Identify the three enzymes that transfer electrons to CoQ from FADH2. |
|
Definition
- Succinate dehydrogenase (complex II)
- Glycerol-phosphate dehydrogenase
- Fatty-acyl CoA dehydrogenase |
|
|
Term
| Identify the ETC component that transfers electrons to CoQ. |
|
Definition
| Complex I (from NADH to ubiquinone), and also Complex II (Succinate dehydrogenase) |
|
|
Term
| Identify the ETC component that transfers electrons to cytochrome c. |
|
Definition
| Complex III (from ubiquinol to cytochrome c) |
|
|
Term
| ETC component that transfers electrons to oxygen? |
|
Definition
| Complex IV (Cytochrome oxidase complex). |
|
|
Term
| In Complex IV (Cytochrome oxidase complex) O2 is tightly bound between ____ & ____, and released after complete reduction to H2O by transfer of 4 e-. |
|
Definition
|
|
Term
| What metal ion actually reduces the oxygen bound by Complex IV (Cytochrome oxidase complex) to water? |
|
Definition
|
|
Term
| Protons are pumped out, driven by the ____ reactions |
|
Definition
|
|
Term
| Pump protons out of ____ into _____. |
|
Definition
mitochondrial matrix
intermembrane space |
|
|
Term
| What is the chemiosmotic hypothesis? |
|
Definition
| The chemiosmotic hypothesis proposes that the proton-translocating activity of electron transport complexes in inner mitochondrial membrane generates proton gradient across the membrane. Protons cannot diffuse back into matrix because membrane is impermeable to ions |
|
|
Term
| Proton gradient contains the energy for ATP synthesis, 10x higher concentration outside, Greater than 10x will ______. |
|
Definition
| change energetics; blocks pumps and electron flow |
|
|
Term
| Oxidative phosphorylation is the use of the energy from ____ of cofactors (____ & ____) to synthesize ATP. |
|
Definition
|
|
Term
| Oxygen consumption coupled to the ____. |
|
Definition
|
|
Term
| Pressure from proton gradient drives_____ forward. |
|
Definition
|
|
Term
| ____ pulls electrons through ETC |
|
Definition
|
|
Term
| Where in the cell does oxidative phosphorylation take place? |
|
Definition
|
|
Term
| What is the system of electron carriers that are coupled to ATP synthesis called? Where are they located? |
|
Definition
| Respiratory chain found in the inner mitochondrial membrane. |
|
|
Term
| ATP synthase is composed of two units: _____ |
|
Definition
|
|
Term
| _____ unit of ATP synthase has 3 catalytic sites on circular array of 3 α and 3 β subunits |
|
Definition
|
|
Term
| F1 (coupling factor 1) is attached to |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| oligomycin-sensitive factor |
|
|
Term
| Is F0 or F1 an integral membrane protein? |
|
Definition
|
|
Term
| 360 degree turn of motor produces ___ molecules of ATP while ____ protons are translocated |
|
Definition
|
|
Term
| _ protons drive the synthesis of 1 ATP |
|
Definition
|
|
Term
| Why is part of ATP synthase called an ATPase? |
|
Definition
| In the absence of a sufficient proton gradient, ATP synthase DOES NOT synthesize but rather hydrolyzes ATP (consumes it). |
|
|
Term
| ATP translocase affect on the membrane potential? |
|
Definition
| Weakens membrane potential because ADP has 3 negative charges at physiological pH, and ATP has about 4. Moves ADP into the matrix to be made into ATP and ATP out for cell use. |
|
|
Term
| ______ allows NADH from cytoplasm (glycolysis) to enter the mitochondrial matrix to participate in ETC. |
|
Definition
| glycerol phosphate shuttle |
|
|
Term
| each FADH2 produces _ ATP |
|
Definition
|
|
Term
| In the Glycerol phosphate shuttle NADH donates electrons to ______ through _____ enzyme. |
|
Definition
Glycerol
DHAP (dihydroxyacetone phosphate) |
|
|
Term
| In the Glycerol phosphate shuttle NADH donates electrons to glycrerol through DHAP (dihydroxyacetone phosphate), which then donates the electrons to _____ to form _____. |
|
Definition
|
|
Term
| In the Glycerol phosphate shuttle NADH donates electrons to glycrerol through DHAP (dihydroxyacetone phosphate), which then donates the electrons to FAD to form FADH2. FADH2 then donates the electrons to _____ to form _____ in an irreversible process. |
|
Definition
|
|
Term
| In the Glycerol phosphate shuttle NADH donates electrons to glycrerol through DHAP (dihydroxyacetone phosphate), which then donates the electrons to FAD to form FADH2. FADH2 then donates the electrons to CoQ to form CoQH2 in an irreversible process. CoQH2 then goes on to _____ |
|
Definition
| Complex III Cytochrome Reductase |
|
|
Term
| Glycerol phosphate shuttle leads to the production of ___ ATP per NADH. |
|
Definition
| 2 (Because is transformed into FADH2 which skips the first complex, NADH Q Reductase |
|
|
Term
| With the Malate-aspartate shuttle, NADH donates electrons to ______ turning it into _______. |
|
Definition
|
|
Term
| With the Malate-aspartate shuttle, NADH donates electrons to OAA turning it into malate, which is then _____. |
|
Definition
| transported across the IMM and donates its electrons to NAD+ to form NADh |
|
|
Term
| Why can't oxaloacetate get across the inner mitochondrial membrane? |
|
Definition
| No transporter & because too large and - charges |
|
|
Term
| oxaloacetate can be converted to _____ for transport back across the IMM to the cytoplasm |
|
Definition
|
|
Term
| There is a antiport aspartate-_____ transporter in the IMM |
|
Definition
|
|
Term
| Give the definition of Respiratory Control. |
|
Definition
| ATP cannot be synthesized without electron flow, and electrons cannot flow without ATP synthesis |
|
|
Term
| If ADP is absent, ____ stops |
|
Definition
|
|
Term
| Oxygen consumption depends on availability of ____. |
|
Definition
|
|
Term
| Very tight coupling between ETC and ____ concentrations |
|
Definition
|
|
Term
| Respiratory control prevents unnecessary consumption of O2 when ______. |
|
Definition
|
|
Term
What is required for respiratory control?
Tight coupling between ____ and the concentrations of ____. |
|
Definition
|
|
Term
| Where is the rate limiting step for the ETC? |
|
Definition
| No rate limiting step, but rate depends on substrate availability. |
|
|
Term
| What is the rate limiting factor in respiratory control? |
|
Definition
Usually, ADP is the rate limiting substrate.
but could be
Possible rate limiting factors include: NADH, Oxygen, ADP, phosphate, capacity of respiratory chain itself when all substrates freely available (Vmax) |
|
|
Term
| What happens to pyruvate dehydrogenase when the energy charge drops and NAD+/NADH increases? |
|
Definition
| Stimulates pyruvate dehydrogenase and regulated enzymes of TCA cycle. |
|
|
Term
| Each complex coupled to a _____. |
|
Definition
|
|
Term
| Proton gradient contains the energy for _____. |
|
Definition
|
|
Term
| Oxygen consumption coupled to ______. |
|
Definition
|
|
Term
| ATP synthase can run backwards, so it is also called mitochondrial ______. |
|
Definition
|
|
Term
| Is malate-aspartate shuttle reversible? |
|
Definition
|
|
Term
| Is Glycerol Phosphate Shuttle reversible? |
|
Definition
| NO, transfer of Electrons from glycerol phosphate to FAD is irreversible |
|
|
Term
| If ADP is absent, ____ stops |
|
Definition
|
|
Term
| Very tight coupling between ____ and the concentrations of _____. |
|
Definition
|
|
Term
| Very tight coupling between ETC and ADP concentrations. But, if oxidative phosphorylation is uncoupled (protons flow around ATP synthase), then ETC rate is ______. |
|
Definition
| as fast as the O2 supply. |
|
|
Term
| Oligomycin inhibits ______ and leads to a --___ ratio. |
|
Definition
| inhibition of ATP synthesis – reduced ATP/ADP |
|
|
Term
| Oligomycin acts on _____. |
|
Definition
|
|
Term
| Dinitrophenol (DNP) is a _____ |
|
Definition
|
|
Term
| Dinitrophenol (DNP) is a Uncouplers and leads to a ______ ratio. |
|
Definition
|
|
Term
| The Phosphate/Oxygen Ratio, or P/O Ratio, refers to the amount of ATP produced from the movement of two electrons through a defined electron transport chain, donated by reduction of an oxygen atom. WIKI |
|
Definition
|
|
Term
| Dinitrophenol (DNP) is a Uncouplers that carries H+ from ____ to ____. |
|
Definition
|
|
Term
| Rotenone is a Pesticide that inhibits electron flow from ____ complexes in _____ complex to ubiquinone |
|
Definition
iron-sulfur
NADH-Q reductase complex (Complex I) |
|
|
Term
| Barbiturates (ex: amytal) inhibit electron flow thru _____ complex |
|
Definition
| NADH-Q reductase Complex (Complex I) |
|
|
Term
| Antimycin A blocks electron flow thru _____ complex |
|
Definition
| blocks electron flow thru QH2-cytochrome c reductase complex (Complex I) |
|
|
Term
| Inhibitors of cytochrome oxidase complex (Complex IV)? |
|
Definition
|
|
Term
| ____ causes Inhibition of translocation of ATP/ADP |
|
Definition
|
|
Term
| Atractyloside, which causes Inhibition of translocation of ATP/ADP leads to ______. |
|
Definition
Reduced ATP/ADP levels in the cytoplasm
Increased ATP/ADP levels in the matrix |
|
|
Term
| Cyanide: inhibition of e- flow (like hypoxia, anoxia), produces _____. |
|
Definition
|
|
Term
| Inhibiting Cytochrome Oxidase (Complex IV) produces |
|
Definition
|
|
Term
|
Definition
1.
ET slows down
2.
NADH increases; ADP increases
3.
MA shuttle reverses; ATP translocase reverses
4.
PFK stimulated; AMP/ADP
5.
NADH and lactic acid increases
6.
Lysosomes go BOOM! (...eventually) |
|
|
Term
| Uncouplers of oxidative phosphorylation prevent ______ despite continued e- flow. |
|
Definition
|
|
Term
| Uncouplers of oxidative phosphorylation lead to a _____ P/O ratio. |
|
Definition
|
|
Term
| 2 Uncouplers of oxidative phosphorylation |
|
Definition
| 2,4-dinitrophenol and pentachlorophenol |
|
|
Term
| 2,4-dinitrophenol and pentachlorophenol are ______ soluble. |
|
Definition
|
|
Term
| 2,4-dinitrophenol and pentachlorophenol are uncouplers that _____ |
|
Definition
| Dissipate proton gradient by ferrying protons across inner mitochondrial membrane |
|
|
Term
| With 2,4-dinitrophenol and pentachlorophenol uncouplers ATP can no longer be synthesized, but e- flow _____ because bc respiratory chain no longer has to ______. |
|
Definition
| pump protons against a steep gradient |
|
|
Term
| with 2,4-dinitrophenol and pentachlorophenol uncouplers proton pumps increase and therefore ______ increases |
|
Definition
|
|
Term
| Arsenate is a structural analog of _____. |
|
Definition
|
|
Term
| Arsenate competes with phosphate for _____. |
|
Definition
|
|
Term
| What happens to the cytochromes upstream of the block? |
|
Definition
| Upstream – highly reduced, continuous electron flow |
|
|
Term
| What happens to the cytochromes downstream of the block? |
|
Definition
| highly oxidized, no electron flow |
|
|
Term
| Name a poison that can block proton flow back into the matrix. |
|
Definition
|
|
Term
| Oligomycin blocks proton flow back into the matrix, by blocking ______ |
|
Definition
| F0 the proton channel of ATP Synthatse |
|
|
Term
| Oligomycin blocks proton flow back into the matrix, by blocking F0 the proton channel of ATP Synthatse, which blocks _____ |
|
Definition
|
|
Term
| Name a poison that facilitates the flow of protons across the inner membrane from the intermembrane space into the matrix |
|
Definition
| DNP and pentachlorophenol (uncouplers) |
|
|
Term
| Since ATP can't be made from these shunted protons following uncouplers, what happens to the energy? |
|
Definition
| as heat, causing hyperthermia |
|
|
Term
| How does pentachlorophenol lead to lactic acidosis and why do these patients have hyperthermia? |
|
Definition
ETC is untouched. High [NAD+]/[NADH] ratio because of increased NADH oxidation and low ATP/ADP ratio (low energy charge) because ATP is not being synthesized, stimulating anaerobic glycolysis (PFK activity). Pyruvate increased -> lactate increased. NADH oxidation and oxygen consumption are increased (in contrast to cyanide poisoning) Failure of oxidative phosphorylation Energy of fuel oxidation is released as heat -> hyperthermia
*Note: Actual NAD+/NADH ratio does not change that much because NADH is quickly regenerated by increased activity of TCA cycle and glycolysis.
* Note: babies have brown fat that contain thermogenin, which uncouples ETC and dissipates energy as heat to keep babies warm. |
|
|
Term
|
Definition
| The number of high energy phosphate bonds formed for each oxygen atom (or each pair of electrons) consumed |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Name a poison that can keep ADP from exchanging with ATP. |
|
Definition
|
|
Term
| What happens to the energy charge in the cell when Atractyloside is working? |
|
Definition
| ADP supply depleted, and ATP synthesis halted. (can't transport atp) |
|
|
Term
| What happens to the electron flow when Atractyloside is working? |
|
Definition
|
|
Term
| Compare the mechanism of arsenate action in the mitochondrion with its action in glycolysis. |
|
Definition
Glycolysis:
- Structural analog
- UNCOUPLING -> pathway can proceed, but without ATP synthesis
- Net ATP yield of glycolysis is 0
Mitochondrion:
- Structural analog
- Competes with phosphate for ATP synthesis
- Analog of ATP is unstable and hydrolyzes spontaneously to ADP and arsenate |
|
|
Term
| Just how does arsenate get into the mitochondrion anyway? |
|
Definition
|
|
Term
| With Pentachlorophenol is the ETC ok? NAD+/NADH ratio? |
|
Definition
|
|
Term
| Does Cyanide poisoning produce lactic acidosis? |
|
Definition
|
|
Term
With Pentachlorophenol posioning:
ATP/ADP _____
PFK _____
Pyruvate _____
Lactate _____ |
|
Definition
Drops
Increases
increased
Increased |
|
|
Term
| Does Pentachlorophenol poisoning produce lactic acidosis? |
|
Definition
|
|
