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42 Cards in this Set
- Front
- Back
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T/F gluconeogenesis is initiated when all glycogen is depleted
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No, it is initiated just before
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What is the principal rxn that is involved in gluconeogenesis?
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pyruvate to glucose
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What are the 3 key substrates for gluconeogenesis, and their respective sources?
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alanine (muscle degradation), glycerol (TAGs) and lactate (pyruvate)
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Which TCA cycle intermediate plays a role in gluconeogenosis?
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oxaloacetate
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where do the carbons from pyruvate in gluconeogenesis enter into the glycolytic cycle?
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Phosphoenolpyruvate (PEP)
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Where does glycerol enter back into the glycolytic pathway?
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glycerol-3-phosphate
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where is the primary site (organ) of gluconeogenesis?
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liver (some activity I the kidney cortex in extreme starvation)
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What is the cost in ATPs to convert pyruvate to glucose?
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6 ATP (note it cost 2 ATPs in glycolysis… with a net gain of two… thus there is a net loss of two ATP)
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Where does lactate come from?
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Muscles and RBCs
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Where does alanine come from?
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muscle breakdown
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Where must the gluconeogenesis precursors go?
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the liver
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What is the Cori cycle?
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the cycling of lactate produced by anaerobic glycolysis, i.e., glucose>blood>lactate>to liver>glucose
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What is the glucose-alanine cycle?
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the cycling of glucose>muscle>muscle degradation>alanine> to liver>(nitro excreted and carbon to glucose) gluconeogenesis> glucose>muscle
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Where does alanine come from in muscle?
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glucose to alanine through linked rxns… amino acid to ∂-Keto Acid as ∂-KG goes to glutamate… as pyruvate goes to alanine
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Anaplerotic?
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rxn that supplies metabolic pathways with intermediate molecules
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If we look at reversing glycolysis, its ∆G= +20. However, gluconeogenesis has a ∆G=-9. So, what draws gluconeogenesis forward?
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high energy phosphates (the hydrolysis of ATP and GTP) and the reducing equivalents.
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What are the 4 major rxns in gluconeogenesis? (name the enzymes only)
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a) pyruvate carboxylase… b) phosphoenolpyrvate carboxykinase (PEPCK)… c) F-1,6-Bisphosphatase… d) G6-phosphatase
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What type of rxn is the pyruvate carboxylase rxn?
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lactate dehydrogenase
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What is needed to convert lactate into pyruvate?
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lactate dehydrogenase and NAD+ (which will be reduced)
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What impact does ethanol ingestion have on the conversion of lactate to pyruvate
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NADH is produced in ethanol metabolism, thus the excess NADH will inhibit pyruvate production (thus inhibit gluconeogenesis) , which also produces NADH… in fact it will drive the rxn in the opposite direction.
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What type of rxn is the conversion of alanine to pyruvate?
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transamination rxn.
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What is the conversion of alanine to pyruvate (transamination) rxn coupled to? And what enzyme catalyzes this?
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∂-KG to glutamate… alanine aminotransferase
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What is the mechanism for glycerol to get into the gluconeogenesis pathway?
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Glycerol --> Glycerol-3-P --> DHAP
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What is required for first step (glycerol --> Glycerol-3-P in the entry of glycerol to the gluconeogenesis pathway?
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glycerol kinase and ATP
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What is required for second step (Glycerol-3-P --> DHAP) in the entry of glycerol to the gluconeogenesis pathway?
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glycerol-3-P dehydrogenase and NAD+
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What can inhibit glycerol entry into the gluconeogenesis pathway? Why?
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alcohol consumption… because it contributes NADH and send the rxn in the opposite direction.
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What is the mechanism for pyruvate to enter the gluconeogenesis pathway?
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Pyruvate --> oxaloacetate --> phosphoenolpyruvate (PEP)
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Why is CO2 required in the pyruvate to oxaloacetate rxn?
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a) pyruvate has 2 carbons and oxaloacetate has 4 carbons.
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What is required to drive the Pyruvate --> oxaloacetate rxn? And where does it occur?
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a) pyruvate carboxylase + CO2 + ATP + biotin (a cofactor)… b) in the mitochondria
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What is required to drive the oxaloacetate --> phosphoenolpyruvate (PEP) rxn? And where does this rxn occur? And why?
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a) PEPCK + GTP (CO2 is lost)… b) in the cytosol and the mitochondria... c) oxaloacetate cannot cross the into cytosol (thus it is coupled transport) like previously discussed but the goal is to get OAA out of the matrix.
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How is the PK in the glycolytic pathway of PEP to pyruvate inhibited?
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PKA activation, which will then phosphorylate PK… results from glcagon signal cascade to cAMP production
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When TAGs are metabolized by glucagon via cAMP, what can occur that will shunt pyruvate into the gluconeogenesis pathway? Why does this make sense?
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The fatty acids from the breakdown of TAG produces NADH, which inhibits pyruvate dehydrogenase, which converts pyruvate into acetyl CoA… thus shunting pyruvate into the gluconeogenesis pathway… b) if you need to breakdown TAG, you might need gluconeogenesis.
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When does gluconeogenesis occur?
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during fasting, prolonged exercise, high protein diet and while under high stress.
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When are amino acids release from muscles?
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low insulin and high cortisol
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when are amino acids available for gluconeogenesis?
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high protein intake… low carb intake
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When is glycerol released from adipose?
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low insulin, high glucagon, epi, and cortisol
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When is lactate produced by RBCs and muscle
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during exercise
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In the gluconeogenesis rxn of pyruvate --> PEP, what activates pyruvate carboxylase?
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cAMP
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Is PEPCK inducible?
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yes
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What effect does cAMP have on PK?
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inhibits it
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In the gluconeogenesis rxn of F-1,6-BisP to F6P (which i is inducible) what inhibits it? What does this oppose?
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F-2,6-BisP… this is in opposition to glycolysis where F-2,6-BisP induces PFK-1
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In the gluconeogenesis rxn of G6P to glucose, is it inducible?
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yes
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