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Stages 1-3 of intermediary metabolism |
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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 |
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Definition
metabolism of glucose to support energy production. intermediates in the pathway can be used to support other metabolic pathways. |
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glucose (and other carbs at intermediate steps) |
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aerobic = pyruvate+2ATP+2NADH, anaerobic = lactate. |
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in glycolysis. 2ATP, 1 for G>G6P, 1 for F6P>F16BP. |
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committing step in glycolysis |
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Definition
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glycolysis step where a single 6C molecule is cleaved into two 3C molecules |
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Definition
F16BP> 2x glyceraldehyde 3-phosphate (each carries one phosphate from F16BP) |
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Term
why does glycolysis only produce 2atp? |
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Definition
it's actually 4, but 2atp are required for the reaction to proceed. 4-2=2. |
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when is NADH produced in glycolysis? |
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Definition
glyceraldehyde3P>1,3bisphosphoglycerate |
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under anaerobic glycolysis conditions, NADH... |
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Definition
is converted back to NAD+ in the Cori cycle. |
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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. |
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Definition
pyruvate enters mitochondria, is converted to acetyl coa and is used in the TCA cycle. |
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Term
regulation of glycolysis, first of three steps |
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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) |
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regulation of glucokinase |
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Definition
stimulated by insulin, inhibited by glucagon |
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regulation of glycolysis, second of three steps |
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Definition
(fructose6p>fructose16bisphosphate) PFK1 |
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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. |
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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. |
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Definition
glucagon actives cAMP which phosphorylates and inactivates PFK2. = decrease in Fru 2,6 bis P = reduction in glycolysis rate |
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Term
regulation of third of three glycolysis steps (and regulation of the regulator) |
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Definition
PEP>pyruvate = pyruvate kinase. stimulated by insulin and decreased by glucagon/epinephrine. |
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Term
in liver glycolysis is catabolic/anabolic |
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Definition
anabolic. in all other tissues, the pathway is used for energy generation and is considered catabolic. |
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Definition
lactate accumulating in blood. caused by (myocardial) infarction, low oxygen tension in blood (lung disease), or impairment in oxidative phosphorylation. |
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Definition
acidic pH = muscle cramps |
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Term
pyruvate kinase deficiency |
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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 |
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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}} |
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Definition
>lactate (anaerobic metabolism), >alanine (links carb and AA metabolism), >OAA (gluconeogenesis), > Acetyl CoA (TCA) |
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oxidation of pyruvate: purpose and location |
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Definition
formation of acetyl coa. mitochondrial matrix |
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Term
substrates and products of oxidation of pyruvate; regulation. |
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Definition
S - pyruvate. P - Acetyl Coa(, NADH); PDH. |
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Definition
comprised of 3 enzymes and multiple cofactors. inhibited by Acetyl Coa, NADH, cAMP-mediated pathways. stimulated by insulin (dephosphorylation). |
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Definition
most common cause of congenital lactic acidosis. brain is particularly sensitive. |
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purpose and location of TCA |
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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 |
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substrates and products of TCA / regulation |
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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. |
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clinical relevance of TCA cycle |
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Definition
many of the enzymes in the cycle are targets for genetic mutation. inborn errors. rare. |
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Term
purpose and location of gluconeogenesis |
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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. |
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Term
substrates and products of gluconeogenesis |
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Definition
s - lactate OR glucogenic AAs OR glycerol. NOT FAT. p - glucose. |
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clinical relevance of gluconeogenesis |
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Definition
inheritable defects result in hypoglycemia during fasts |
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what does gluconeogenesis require |
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Definition
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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. |
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Term
energy requiring steps of gluconeogenesis (4) |
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Definition
pyruvate>OAA>PEP (2). 2 3-phosphoglycerate to 2 1,3bisphosphoglycerate requires 2ATP. 2 1,3bisphosphoglycerate> 2 glyceraldehyde requires 2NADH. |
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regulation of gluconeogenesis |
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Definition
inhibited by insulin, stimulated by glucagon and cAMP-mediated signaling. PFK2 and FBP2 (do opposite of what they do in glycolysis.) |
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regulation of pyruvate carboxylase |
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Definition
allosterically activated by acetyl coa (high in fasted state) |
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Definition
transcription of its mRNA is increased by glucagon and decreased by insulin |
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regulation of fructose 1,6-bisphosphatase |
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Definition
inhibited by high AMP, fructose26bisphosphate, stimulated by high ATP. |
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Term
why can't G6P leave the cell? |
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Definition
the phosphate group has a negative charge, so it's no longer soluble through the cell membrane |
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Term
pyruvate is oxidized/reduced to lactate? |
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Definition
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Definition
acetyl coa donates 2C to the 4C oxaloacetate, which leads to a series of oxidation reactions |
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3 regulated enzymes of TCA |
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Definition
citrate synthase, isocitrate dehydrogenase ("pacemaker"), A-ketoglutarate dehydrogenase |
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gluconeogenesis and glycolysis are... |
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Definition
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protein kinase cascade is stimulated by |
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Definition
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gluconeogenesis is stimulated by... |
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Definition
counter-regulatory hormones |
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Definition
allosteric interactions, covalent (phosphorylation), enzyme levels, cellular compartmentalization, organ specific metabolism |
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Definition
insufficiency of insulin, excess glucagon, elevated blood glucose |
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Term
major consequence of a deficiency in the kinase in liver that synthesizes fructose26biphosphate? |
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Definition
fructose16bisphosphatase activity will increase |
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