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9. Glycolysis, TCA, Gluconeogenesis (broad)
BrownMed
54
Biochemistry
Undergraduate 4
09/28/2010

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Term
Stages 1-3 of intermediary metabolism
Definition
1. hydrolysis of complex molecules to their component building blocks, 2. conversion of building blocks to acetyl coa (or other simple intermediates), 3. oxidation of acetyl coa and oxidative phosphorylation
Term
purpose of glycolysis
Definition
metabolism of glucose to support energy production. intermediates in the pathway can be used to support other metabolic pathways.
Term
location of glycolysis
Definition
cytoplasm of all cells
Term
substrates of glycolysis
Definition
glucose (and other carbs at intermediate steps)
Term
products of glycolysis
Definition
aerobic = pyruvate+2ATP+2NADH, anaerobic = lactate.
Term
energy investment
Definition
in glycolysis. 2ATP, 1 for G>G6P, 1 for F6P>F16BP.
Term
committing step in glycolysis
Definition
F6P>F16BP
Term
glycolysis step where a single 6C molecule is cleaved into two 3C molecules
Definition
F16BP> 2x glyceraldehyde 3-phosphate (each carries one phosphate from F16BP)
Term
why does glycolysis only produce 2atp?
Definition
it's actually 4, but 2atp are required for the reaction to proceed. 4-2=2.
Term
when is NADH produced in glycolysis?
Definition
glyceraldehyde3P>1,3bisphosphoglycerate
Term
under anaerobic glycolysis conditions, NADH...
Definition
is converted back to NAD+ in the Cori cycle.
Term
anaerobic glycolysis
Definition
occurs when oxygen is low or mitochondria are low (RBCs, exercising muscle). Cori cycle = pyruvate>lactate in muscle, lactate to pyruvate in liver and then back to muscle.
Term
aerobic glycolysis
Definition
pyruvate enters mitochondria, is converted to acetyl coa and is used in the TCA cycle.
Term
regulation of glycolysis, first of three steps
Definition
hexokinase and glucokinase. H - in all tissues, low Km and Vmax. G - in liver and beta cells of pancreas. high Km and Vmax. (glucose>g6p)
Term
regulation of hexokinase
Definition
inhibited by glucose 6 P
Term
regulation of glucokinase
Definition
stimulated by insulin, inhibited by glucagon
Term
regulation of glycolysis, second of three steps
Definition
(fructose6p>fructose16bisphosphate) PFK1
Term
regulation of PFK1
Definition
allosterically activated by high AMP, (allo) inhibited by high ATP, high citrate. in liver, inhibited by glucagon and stimulated by insulin. stimulated by fructose 2,6 bisphosphate.
Term
PFK2
Definition
bifunctional enzyme: contains kinase and phosphatase (FBP2). is active when dephosphorylated and inactive (w/ FBP2 activated) when phosphorylated. favors the formation of Fru 2,6 bis P.
Term
regulation of PFK2
Definition
glucagon actives cAMP which phosphorylates and inactivates PFK2. = decrease in Fru 2,6 bis P = reduction in glycolysis rate
Term
regulation of third of three glycolysis steps (and regulation of the regulator)
Definition
PEP>pyruvate = pyruvate kinase. stimulated by insulin and decreased by glucagon/epinephrine.
Term
in liver glycolysis is catabolic/anabolic
Definition
anabolic. in all other tissues, the pathway is used for energy generation and is considered catabolic.
Term
lactic acidosis (4)
Definition
lactate accumulating in blood. caused by (myocardial) infarction, low oxygen tension in blood (lung disease), or impairment in oxidative phosphorylation.
Term
lactate in muscle
Definition
acidic pH = muscle cramps
Term
pyruvate kinase deficiency
Definition
common cause of hemolytic anemia. mature erythrocytes lack mitochondria, so are dependent on glycolysis for ATP production. without it, transporters in the RBC membranes stop functioning, so the membrane gets all spiny and the spleen eats the cell. autosomal recessive. also causes jaundice
Term
arsenic poisoning
Definition
arsenate closely resembles inorganic phosphate and competes with it in enzymatic reactions. leads to inhibition of pyruvate dehydrogenase. is a competitive inhibitor of glyceraldehyde 3-phosphate dehydrogenase (which converts 1,3bisphosphoglycerate to 3-phosphoglycerate). = no ATP from that glycolysis step. {{brain is particularly affected}}
Term
fates of pyruvate (4)
Definition
>lactate (anaerobic metabolism), >alanine (links carb and AA metabolism), >OAA (gluconeogenesis), > Acetyl CoA (TCA)
Term
oxidation of pyruvate: purpose and location
Definition
formation of acetyl coa. mitochondrial matrix
Term
substrates and products of oxidation of pyruvate; regulation.
Definition
S - pyruvate. P - Acetyl Coa(, NADH); PDH.
Term
PDH / regulation.
Definition
comprised of 3 enzymes and multiple cofactors. inhibited by Acetyl Coa, NADH, cAMP-mediated pathways. stimulated by insulin (dephosphorylation).
Term
PDH deficiency
Definition
most common cause of congenital lactic acidosis. brain is particularly sensitive.
Term
purpose and location of TCA
Definition
energy transfer from acetyl-coa to high energy compounds that drive ATP production. intermediates serve as precursors for many biosynthetic pathways. location - mitochondrial matrix
Term
substrates and products of TCA / regulation
Definition
S - acetyl coa. P - 3NADH, FADH2, GTP, 2CO2 / rates of glycolysis and TCA are integrated, so ATP and NADH inhibit TCA allosterically, citrate inhibits pfk1 in glycolysis, and the rate of pyruvate>acetylcoa affects TCA.
Term
clinical relevance of TCA cycle
Definition
many of the enzymes in the cycle are targets for genetic mutation. inborn errors. rare.
Term
purpose and location of gluconeogenesis
Definition
production of glucose from non-carb precursors; for glucose-requiring tissues (brain and nervous system, exercising skeletal muscle, RBCs, testes, renal medulla, embryonic tissues). location - liver and kidney - mitochondria and cytosol.
Term
substrates and products of gluconeogenesis
Definition
s - lactate OR glucogenic AAs OR glycerol. NOT FAT. p - glucose.
Term
clinical relevance of gluconeogenesis
Definition
inheritable defects result in hypoglycemia during fasts
Term
what does gluconeogenesis require
Definition
4ATP, 2GTP, 2NADH
Term
bypass reactions (4)
Definition
*pyruvate>OAA>PEP. 1. pyruvate carboxylase, 2ATP. Takes place in liver mitochondria. 2. PEP carboxykinase (CK), 2GTP. Takes place in liver cytosol. *fructose16bp>fructose6p via fructose16bisphosphatase. Takes place in liver cytosol. *glucose6p>glucose via glucose6phosphatase. Takes place only in the endoplasmic reticulum of kidney.
Term
energy requiring steps of gluconeogenesis (4)
Definition
pyruvate>OAA>PEP (2). 2 3-phosphoglycerate to 2 1,3bisphosphoglycerate requires 2ATP. 2 1,3bisphosphoglycerate> 2 glyceraldehyde requires 2NADH.
Term
regulation of gluconeogenesis
Definition
inhibited by insulin, stimulated by glucagon and cAMP-mediated signaling. PFK2 and FBP2 (do opposite of what they do in glycolysis.)
Term
regulation of pyruvate carboxylase
Definition
allosterically activated by acetyl coa (high in fasted state)
Term
regulation of PEPCK
Definition
transcription of its mRNA is increased by glucagon and decreased by insulin
Term
regulation of fructose 1,6-bisphosphatase
Definition
inhibited by high AMP, fructose26bisphosphate, stimulated by high ATP.
Term
why can't G6P leave the cell?
Definition
the phosphate group has a negative charge, so it's no longer soluble through the cell membrane
Term
pyruvate is oxidized/reduced to lactate?
Definition
reduced
Term
TCA cycle - general
Definition
acetyl coa donates 2C to the 4C oxaloacetate, which leads to a series of oxidation reactions
Term
3 regulated enzymes of TCA
Definition
citrate synthase, isocitrate dehydrogenase ("pacemaker"), A-ketoglutarate dehydrogenase
Term
gluconeogenesis and glycolysis are...
Definition
reciprocally regulated
Term
protein kinase cascade is stimulated by
Definition
insulin
Term
gluconeogenesis is stimulated by...
Definition
counter-regulatory hormones
Term
common regulatory themes
Definition
allosteric interactions, covalent (phosphorylation), enzyme levels, cellular compartmentalization, organ specific metabolism
Term
diabetes mellitus
Definition
insufficiency of insulin, excess glucagon, elevated blood glucose
Term
major consequence of a deficiency in the kinase in liver that synthesizes fructose26biphosphate?
Definition
fructose16bisphosphatase activity will increase
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