BIOLCHEM 415 1st Edition Lecture 15 Outline of Last Lecture I. Glycolysis is the metabolic pathway that converts sugars into pyruvateII. Glycolysis occurs in two stages and produces ATPIII. NADH needs to be replenished for continual glycolysisOutline of Current Lecture IV. Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursorsV. Two ATP-consuming reaction in glycolysis become hydrolytic reactionsVI. Glyclysis and gluconeogenesis are tightly/reciprocally regulatedCurrent LectureHow much glucose do we need?- ~160 g/day (brain uses ~120 g/day)- synthesize because ATP storage low- dietary blood glucose is very short-livedGluconeogensis- synthesis of glucose from non-carbohydrate precursors- non-carbohydrate precursors:- carbon skeletons of some amino acids- glycerol (in 2 steps)- hydrolysis of triacylglycerols - almost a reversal of glycolysis- irreversible steps of glycolysis must be bypassedBiotinThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- an important CO2 carrier- required by pyruvate carboxylase - carries the CO2 necessary for the synthetic reactions- formation of oxaloacetate occurs in 3 stagesOxaloacetate (malate) shuttle- pyruvate OAA in mitochondria- following reactions of gluconeogenesis in the cytosol- connects reaction in mitochondria to cytosol- compartmentation- also shuttles NADH - PEP synthesized from OAA by phosphoenolpyruvate carboxykinasePhosphorylations of glycolysis are replaced by hydrolysis- phosphorylations are irreversible- hydrolysis of fructose 1,6-bisphosphate is irreversible - allosterically regulated enzymeGeneration of free glucose- final step in gluconeogenesis- glucose 6-phosphate lumen of endoplasmic reticulum- integral membrane protein on inner surface- catalyzes formation of glucose- limited tissue distribution- sometimes can’t be exported- cant be converted to glycogen for internal energy storage- contained in liver and kidney which can export glucoseCori Cycle links glycolysis in muscle to gluconeogenesis in liver- in liver- O2 available- ATP available- lactate glucose- in muscle- ATP needed- O2 deficit- glucose lactateGluconeogensis and Glycolysis reciprocally regulated- while one is highly active the other is relatively inactive- enzymes potential control sites- catalyze irreversible reactionPhosphofructokinase- regulates glycolysis in muscle- allosterically inhibited by ATP and stimulated by AMP- higher quantity when ATP needed- feed forward- certain isomers stimulate enzymes so downstream reactions are smootherRegulation of glycolysis in muscle- phosphofructokinase, hexokinase, and pyruvate kinase are regulated- hexokinase allosterically inhibited by glucose 6-phosphate- pyruvate kinase inhibited by allosteric ATP signals and alanine- stimulated by fructose 1,6-bisphosphateRegulation of glycolysis in liver- hexokinase- allosteric enzyme- phosphorylating glucose in the liver- glucokinase- only active after a meal- when blood glucose level high- phosphofructokinase- citrate is a key regulator- inhibitor- stimulated by fructose 2,6-bisphosphate- pyruvate kinase- allosterically and by covalent modification- inhibited by ATP- low blood glucose leads to phosphorylation and inhibition- covalent modification- kinase less active Reciprocal Regulation of glycolysis and gluconeogenesis- stimulated by different (opposite) signals- one is active at a time- due to shared use of signaling moleculesHormonal regulation- this kinase is a bifunctional enzyme- synthesizes fructose 2,6-bisphosphate and the phosphatase the hydrolyzes is onthe same polypeptide chain- glucagon pathway leads to the phosphorylation of bifunctional enzyme- inhibits kinase and stimulates phosphataseGlucagon- acts via 7TM receptors and G-proteins- signals low blood glucose - means that it needs gluconeogenesisGlucose and ATP regulate insulin release- insulin stimulates glucose uptake and glycolysis- normally inhibits gluconeogenesis- type 2 diabetes insulin fails to act (insulin resistance)- unstopped gluconeogenesis = high blood
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