Biochemistry – Gluconeogenesis – Flashcards
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glucokinase, PFK1, and pyruvate kinase
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enzymes found in glycolysis but not gluconeogenesis
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gluconeogenic substrates
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-Lactate (pyruvate) - Cori cycle -Gluconeogenic amino acids (all, except leucine and lysine) -Glycerol (from the breakdown of triglycerides) -All TCA intermediates (not acetyl-CoA)
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liver
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major gluconeogenic organ
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location of gluconeogenesis
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primarily in the cytosol, but some precursors are made in the mitochondria (place)
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gluconeogenesis does not occur in
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muscle cells because they lack glucose 6-phosphatase or glucagon receptors
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gluconeogenesis is stimulated by
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falling levels of glucose, increased glucagon levels, decreased insulin levels
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glucose 6-phosphate
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glycolysis and gluconeogenesis is regulated by
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cytosolic NADH
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electron shuttle that turns lactate into pyruvate
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thiamine
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used in decarboxylation reactions
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biotin
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used in carboxylation reactions
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NADH
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electron shuttle required for gluconeogenesis
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lactate dehydrogenase
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makes NADH if lactate is the carbon source
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mitochondria
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Where does gluconeogenesis get NADH if alanine is the carbon source?
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ethanol effect on gluconeogenesis
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It increases NADH levels, which inhibits the conversion of lactate to pyruvate, thus inhibiting gluconeogenesis
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major regulator of gluconeogenesis
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conversion of fructose 1,6-phosphate to fructose 6-bisphosphate
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How is the PFK-1 reaction bypassed?
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in a simple hydrolytic reaction catalyzed by fructose 1,6-bisphosphatase
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How is the glucokinase reaction bypassed?
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in a simple hydrolysis reaction catalyzed by glucose 6-phosphatase
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Where is glucose 6-phosphatase located?
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On the ER and found only in the liver
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Where do the carbon atoms for gluconeogenesis come from?
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lactate or amino acids
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fatty acid oxidation
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What provides the necessary energy for gluconeogenesis?
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major allosteric modulator of PFK-1 and fructose 1,6-bisphosphatase?
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fructose 2,6-bisphosphate
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PFK2
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Regulates fructose 2,6-bisphosphate production; not active when phosphorylated
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What happens when PFK-2 is inhibited?
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-leads to low levels of fructose 2,6-bisphosphate, which inactivates PFK-1 and activates fructose 1,6-bisphosphatase
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biotin
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cofactor for carboxylation enzymes
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What are the metabolic consequences of biotin deficiency?
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accumulation of lactate, acetyl CoA, and ketones (diabetic ketoacidosis); failure in fatty acid synthesis, developmental retardation, lethargy, hallucinations, rash