Term
| What are the two ways the body makes ATP? |
|
Definition
Chemical energy-Substrate Level Phosphorylation
Redox energy-reducing equivalents |
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Term
| What is the end product of glycolysis dependent upon? |
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Definition
| How the tissues recycles NAD for the GAPDH reaction so that glyclysis can continue. |
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Term
| In which state is ATP made/NAD/NADH turned over? (Fed or Fasting) |
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Definition
| Both. It doesn't matter b/c we always have to be ready for muscle contraction |
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Term
| How does cytoplasmic NADH get back to NAD? |
|
Definition
| Passing on reducing equivalents |
|
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Term
| 2 Main mechanisms for NAD recycling? |
|
Definition
Cell has mitochondria and oxygen and ready
RBC with no mitochondria so no way you can do ox phos recycling |
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Term
| Fate of pyruvate in aerobic tissues |
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Definition
| Reducing equivalents from cytoplasmic NADH eventually end up in mitochondria where they pass down ETC to O2 to form H2O |
|
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Term
| Role of the shuttle mechanisms? |
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Definition
Transport NADH across inner mitochondrial membrane, since it is impermable.
NAD/FAD is also recycled allowing shuttles to continue |
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Term
|
Definition
Oxaloacetate->Malate (NADH goes to NAD)
Malate cross into mitochindria (w/ reducing equiv)
Malate goes back to oxaloacetate (NAD to NADH)
2.5 ATP per NADH |
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Term
|
Definition
Dihydroxyacetone Phosphate->G3P (NADH to NAD)
Glycerol 3 phosphatase dehydrogenase complex takes FAD->FADH2 (this goes to complex 3 at UB)
This makes 1.5 ATP/NADH |
|
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Term
| End product of aerobic glycolysis? |
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Definition
|
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Term
| What happens after pyruvate is formed? |
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Definition
| Taken into mitochondria and converted to acetyl CoA |
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Term
| Where are reducing equivalents recovered in the shuttle systems? |
|
Definition
|
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Term
|
Definition
Make lots of ATP
Recycle NAD/FAD so ATP production can continue |
|
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Term
| Examples of electron transport limited conditions? |
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Definition
| Hypoxia Cyanide poisoning |
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Term
| Fate of pyruvate in electron transport limited conditions, anaerobic conditions, or anaerobic oral bacteria? |
|
Definition
Reduced coenzymes NADH and FADH2 build up b/c can't pass into ETC; Production of NADH and FADH2 are inhibited (PDH ICDH); NAD depletes
NADH passes it's reducing equivalents to pyruvate which forms lactate; lactate dehydrogenase catalyzed reaction |
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Term
| End product of anaerobic glycolysis? |
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Definition
|
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Term
Net ATP made in anaerbic glycolysis?
By what process are these made? |
|
Definition
2
Substrate level phosphorlation |
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Term
| Result of anaerbic conditions? |
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Definition
2 vs. 32 ATP; so much lactate overwhelms the system (lactic acidosis)
Oral bacteria metabolize sugar via anaerbic glycolysis, acid effects teeth.
Sometimes we die. (not teeth thing) |
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Term
|
Definition
Lactate dehydrogenase
When conditions are anaerbic
Lactate is the end product |
|
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Term
|
Definition
Pyruvate Dehydrogenase
Aerbic conditions
Water is end product |
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Term
| Overall goal of fuel metabolism after meal? |
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Definition
|
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Term
| Ways blood glucose is lowered after a meal? |
|
Definition
-Stimulate glucose uptake into ALL cells (especially muscle/adipose)
-Turn on all pathways that use glucose
-Convert the excess calories to storage forms->glycogen and fat, for use between meals
-Turn off pathways that generate glucose (prevents hyperglycemia) |
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Term
| Regulation of Fed State pathways? |
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Definition
Insulin turns on
Glucagon turns off |
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Term
| Pathways of the fed state |
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Definition
-Glycolysis
-Glycogen Synthesis
-Pentose Shunt (Provide NADPH for fatty acid biosynthesis)
-PDH turned on
-TAG/FA biosynthesis |
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Term
| What cells use the pentose shunt pathway? |
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Definition
|
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Term
| Where does the pentose shunt reaction occur? |
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Definition
|
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Term
Oxidative Branch of the Pentose shunt?
Reversible?
Reaction?
Rate limiting? |
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Definition
Irreversible
Glucose to ribulose 5p
C6 glucose oxidized to C5 ribulose5p (losing CO2)
Begins with rate limiting step glucose 6pdehydrogenase
Maintain high NADPH/NADP |
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|
Term
Non-oxidative branch of pentose shunt reaction?
What is it for?
Reversible?
Enzymes
Reaction? |
|
Definition
Reversible (interconvert sugars containing 3-7 carbons)
Rubulose 5p to ribose 5P
Nucleotide biosynthesis
Transketoases-TPP as cofactor
Transaldolases |
|
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Term
| What do transketoases require? |
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Definition
| Thiamin Para Phosphate as a cofacor |
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Term
| Why is the pentose shunt path called a "shunt"? |
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Definition
| Becuse the Ribose 5 phosphate is NOT needed, can be "recovered" for energy by conversion back to glycolytic intermediates |
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Term
| Where is Pentose shunt regulated? How? |
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Definition
Glucose 6 phosphate Dehydrogenase
through induction
Allosteric feedback
Happens at the beginning so carbons aren't wasted. |
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Term
| Why is the reducing atmosphere for the RBC important? (2 reasons) |
|
Definition
1.Protects cell membranes against oxidative species (superoxides), ROS which are easy to form in RBC b/c of their high [O2].
2. Keep Fe2+ in functional state; doesn't work if Fe3+ (NADPH associated enzymes do this) |
|
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Term
| How many people have G6PHD deficiencies? |
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Definition
100 million people
11% of African Americans have it |
|
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Term
| Drug induced hemolytic anemia? |
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Definition
| Drugs such as anti-malarials induce oxidative stress. Deficiency manifests, cell membranes are dameged by ROS and cell is lysed. |
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Term
|
Definition
| Insoluble storage form of glucose |
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Term
| What does glycogen resemble? How? |
|
Definition
| Amylopectin. Becuause of the linear alpha 1,4 linkages and the alpha 1,6 linkages |
|
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Term
| Significance of non reducing ends of glycogen. |
|
Definition
Plentiful.
Where action of building or breaking down of glycogen happens |
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Term
| Where does glycogen synthesis occur? |
|
Definition
|
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Term
| Where is glycogen stored? |
|
Definition
| Cytoplasmic granules as needed for fuel. |
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Term
| What is the primary purpose of liver fatty acid and TAG biosynthesis and adpipose TAG re-synthsis? |
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Definition
| Storage along with glycogen, of excess dietary fuel for use during fasting states |
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Term
| Where in the body does endogenous FA synthesis occur? |
|
Definition
Liver, with excess calories/
Mammary gland also |
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Term
| Where in the cell does fatty acid biosynthesis occur? What is usually made? What are the precursors? |
|
Definition
Cytoplasm
C-16 palmitate
NADPH; 2 Carbon Acetyl CoA (made in the mitochondria by PDH)
-Acetyl crosses in the form of citrate; Citrate in mito converted to Acetyl CoA and OAA using ATP and Citrate lyase |
|
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Term
| Delta G of ATP citrate lyase? |
|
Definition
Very positve. Requires ATP
Opposite of citrate synthase (with -DetlaG) |
|
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Term
| How does FA biosynthesis occur? |
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Definition
| Made by repatitive addition of two carbon units to growing end |
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Term
| In FA biosynthesis how is the ACP attached to the chain? |
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Definition
|
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Term
| In FA synthesis what is attached to the growing hydrocarbon chain? |
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Definition
| Acyl Carrier Protein (ACP) |
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|
Term
First step of FA Synthesis. Enzyme?
What happens? |
|
Definition
Formation of malonyl CoA by acetyl CoA carboxylase.
-ATP dependent rxn
-Add CO2- group from bicarb
Acetyl CoA carboxylase =key regulated enzyme
-Co2 release from Mal-CoA as 22 C's are added to growing FA energetically drives 2C addition Rxn |
|
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Term
|
Definition
| Multi-enzyme complex does the chain elongating. |
|
|
Term
| Cofactor of acetyl CoA carboxylase? |
|
Definition
|
|
Term
| In FA biosynthesis, what are acyl groups carried as? How does this relate to the cofactor? |
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Definition
| Thioesters; Using SH of cysteine and of the cofactor phosphopantethiene in ACP |
|
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Term
| Initiation Rxn of FA biosynthesis |
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Definition
| Charge ACP with acetyl CoA and malonyl CoA, and start the chain with the 1st condensation Rxn (adding 2 carbons to Acetyl-ACP from 3 carbon malonyl CoA, driven by release of CO2) |
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Term
| What happens after the initial 2 carbon addition in FA synthesis? |
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Definition
| Remodeling of the growing chain occurs. This involves Reduction, Dehydration, Reduction. (Using NADPH,losing water, using NADPH) |
|
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Term
| What are the reducing equivalnets in FA biosynthesis? |
|
Definition
|
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Term
| How are additional carbons added to the chain in FA synthesis? |
|
Definition
| Malonyl ACP site is re-charged and the next cycle beings with 2 C addition from malonyl-CoA as elongation continues, finally releasing a completed fattyacylCoA |
|
|
Term
| Cost to make 16 carbon palmitate |
|
Definition
-8 Acetyl CoA
-7 Malonyl CoA
-7 ATP used
-17 NADPH |
|
|
Term
| In what form are fatty acids stored in adipose tissues? |
|
Definition
|
|
Term
| Where does TAG synthesis occur? What are they made from? |
|
Definition
| In the liver from excess dietary fuel |
|
|
Term
| What is the first step of TAG synthesis? |
|
Definition
| Phosphatidate is made from glycolytic DHAP and fatty acyl CoA esters(activated from of fatty acids) |
|
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Term
| How do you make a TAG from phosphatidate? |
|
Definition
| Replace PO3 with another fatty acyl group |
|
|
Term
| How are liver tags packaged? |
|
Definition
Within the liver into a carrier called VLDL
These deliver TAG via blood to adipose and other tissues |
|
|
Term
|
Definition
| Free fatty acids are cleaved off the VLDL-TAG complex and taken up by adipose cells. This is used to re-make TAGS as above for storage until they are needed. |
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Term
| Ways to drop your blood glucose |
|
Definition
Increase glucose uptake into cells
turn on glucose use for energy
Store excess calories as glycogan and fat
Turn off glucose production and production of TAG based fuels (fatty acids, ketone bodies. ) |
|
|
Term
| Major regulatory hormone governing the fed, anabolic state? |
|
Definition
|
|
Term
|
Definition
| Peptide hormone releaed by pancreas in response to rise in blood glucose |
|
|
Term
| Insulin regulatory mechanisms |
|
Definition
-Controls substrate supply
-Induction/Repression of certain regulated enzymes
-Promoting dephosphorylation of phosphorylated proteins |
|
|
Term
| When does insulin increase glucose uptake into cells? |
|
Definition
| In muscle/adipose tissues by increasing glut 4 |
|
|
Term
What does insulin do to the liver?
(Glycolysis, Glycogen, Glucose??) |
|
Definition
Increases muscle/adipose glycolysis
Increases glycogen synthesis, fatty acid/TAG biosynthesis and decrease glucose production |
|
|
Term
What does insulin do to muscles/adipose?
(glucogen, TAG) |
|
Definition
| Decreases glycogen breakdown and TAG breakdown (lipolysis) |
|
|
Term
Regulation of glycogen synthase
Kinase/Phosphatase activity. |
|
Definition
Turn on when glucose is abundant (store glycogen)-dehphosphorylation activates
Turn off between meals(break down glycogen for fuel)-phosphorylated is inactive |
|
|
Term
| What effect goes glycogen have on the effect of insulin? |
|
Definition
| Antagonizes insulin effects |
|
|
Term
| What do glucagon/epinephrine do to glycogen synthase? |
|
Definition
| Phosphorylate it--inactivate it. |
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|
Term
| Overall glucose to fat pathway: |
|
Definition
1.Glycolysis
2.PDH
3.Citrate synthase(TCA cycle)
4.Citrate moves into cytoplasm
5.ATP citrate lyase
6.Acetyl CoA carboxylate/fatty acid sunthase
7.With glycerol 3-P, make TAG's for adipose storage |
|
|
Term
| Key regulated enzyme in FA biosynthesis? |
|
Definition
|
|
Term
| Regulation of acetyl CoA carboxylase? |
|
Definition
1. Citrate allosterically activates acetyl CoA carboxylase (feed forward)
2. Palmityl CoA inhibits allosterically (feedback)
3.Dephosphorylation promoted by insulin activates
-Phosphorylation..glucagon inactivates |
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|
Term
| Insulin induction effects what enzymes in the overall glucose to TAG pathway? |
|
Definition
1.Glucokinase and pyruvate kinase (glycolysis)
2.ATP citrate lyase
3.Glucose 6 phosphate dehydrogenase (pentose shunt for NADPH)
4.Acetyl CoA carboxylase
5.F.A. Synthase |
|
|
Term
| Can insulin/glucagon affect things in the mitochondria? |
|
Definition
| No. they can't get inside. |
|
|
Term
| Goals of fuel metabolism in the fasting state? |
|
Definition
Maintain blood glucose levels, esp for tissues that depend on glucsoe for fuel (RBC's, brain)
Provide alternative TAG based fuels to spare available blood glucose |
|
|
Term
| Pathways for the fasting state: Where do they occur? |
|
Definition
-Gluconeogenesis (liver)
-Glycogenolysis (liver)
-Adipose TAG lipolysis (provides FFA)
-Fatty Acid beta oxidation (aerobic tissues; esp muscles and liver)
-Ketone body production (liver)
-Ketone body use (aerobic tissues; except liver) |
|
|
Term
| What does glucagon work on? |
|
Definition
| Directly on liver and adipose only. Affects fuel supply of other tissues (FA, Ketone bodies, and glucose) |
|
|
Term
| What are a main storage form of energy? Why |
|
Definition
| TAG's, b/c of their highly reduced nature |
|
|
Term
|
Definition
Hormone sensitive lipase; releases FFA
3 times to glycerol |
|
|
Term
FFA transport after release from adipose tissue?
In blood? Once inside cell? |
|
Definition
In blood, FFA are transported when bound to serum albumin. Readily taken up by cells
-Once inside cell, they are activated by conversion to CoA thio-esters. then they are transported into the mitochondrion using acylarnitine system (b/c CoA's can't cross mitochondrian) |
|
|
Term
| Why kind of cavities do alpha helicies have? What does this allow them to do? |
|
Definition
| Hydrophobic. Allows them to carry hydrophobic particles, such as drugs |
|
|
Term
Beta Oxidation of fatty acids.
Location
Reactions
Other key products |
|
Definition
Mitochondrial matrix in a spiral pathway
Oxidation/Hydration/Oxidation
NADH and FADH2 |
|
|
Term
| Compare Beta oxidation and FA synthesis. |
|
Definition
Basically opposite.
Reduction in synthesis
Oxidation (pulls off red. equivalents to make ATP) |
|
|
Term
| Products of Beta Oxidation of an 18 C stearate |
|
Definition
9 Acetyl CoA
8 NADH
8FADH2
9GTP from TCA cycle. |
|
|
Term
| What regulates Beta Oxidation? |
|
Definition
| SOLELY by the supply of fatty acids that get into the mitochondrion. Substrate supply |
|
|
Term
| Odd chain fatty acid metabolism |
|
Definition
3 C propionyl-CoA (final product)->Succinyl CoA via poppionyl-CoA carboxylase
Biotin cofactor |
|
|
Term
How and where are ketone bodies produced?
Examples. |
|
Definition
Made in the liver mitochondria from acetyl CoA that is produced there (buildup of it)
Beta hydroxy butyrate
Acetoacetate
Acetone |
|
|
Term
| Conditions that favor liver ketone body production during fasting states? |
|
Definition
1. The rate of the TCA cycle is decreased
2. Acetyl CoA builds up with high fatty acid oxidatoin
3.Acety CoA->ketone bodies (converted) for the liver to export to other tissues. This conserves our blood glucose |
|
|
Term
| Why is the TCA cycle reduced when in the fasting state and making ketone bodies? |
|
Definition
-OAA is shuttled out to make glucose, which decreases level of TCA cycle intermediates.
-Redcuing equivalents, NADH and FADH2 from the TCA cycle are not needed--plenty are produced in fatty acid oxidation to meet the liver's energy needs |
|
|
Term
| Use of ketone bodies as an alternate fuel for fasting state metabolism |
|
Definition
-Liver can NOT break down ketone bodies-this is GOOD b/c we do not want the liver to use/breakdown the ketones before it gets exported out of the body
-Other aerobic tissues cleave ketone bodies back to acetyl-CoA for oxidation in the TCA cycle/os phos for energy. |
|
|
Term
| What does liver fatty acid oxidation provide? |
|
Definition
| Products needed for glucose production during fasting. |
|
|
Term
| How is blood glucose concentration maintained between meals? |
|
Definition
-Dietary carbs can maintain blood glucose levels for a few hours (2-4)
-Beyond this time, blood glucose is supplied by the liver in 2 ways
-breakdown of glycogen
-gluconeogenesis |
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