2-423-08GluconeoStudent - Gluconeogenesis and The Cori...

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Gluconeogenesis and The Cori Cycle Objectives Understand the role of gluconeogenesis in normal physiological processes What metabolites can act as gluconeogenic precursors? What cannot? Know how the irreversible steps of glycolysis are bypassed in gluconeogenesis, and how these are regulated Know the net equation, energy requirements of gluconeogenesis Understand the reciprocal regulation of glycolysis, gluconeogenesis Outline the Cori cycle, explain its biological significance Connect the gluconeogenesis story to the ketone body story I. Where we are Have been studying how fuels are broken down in cells to produce ATP--(oxidative) catabolism. Now turning the corner to look at biosynthetic pathways that require an input of energy and/or reducing power--(reductive) anabolism. A couple of useful generalizations: 1. Pathway of biosynthesis is different than pathway of degradation--in at least one unique step 2. Anabolic and catabolic pathway is controlled by different regulatory enzymes--but these sometimes have the same effector (modulator) that works oppositely on the regulatory enzymes; called coordinate or reciprocal regulation II. Gluconeogenesis A. Review of Glycolysis: -a catabolic pathway used to break down glucose into 2 molecules of pyruvate; -net 2 ATP, 2 NADH (= 4 or 6 ATP) -ATP then used for cellular work B. What is Gluconeogenesis: -at 7 steps, the reverse of glycolysis -an anabolic pathway (biosynthetic) -synthesizes glucose from nonhexose precursors. -occurs primarily in liver which maintains blood glucose levels. Blood glucose critical for erythrocytes and brain because they can't make it, cannot use fatty acids as fuel -occurs when there is a high demand for glucose by particular tissues (brain, RBCs), such as when dietary intake insufficient Gluconeogenesis produces glucose from pyruvate, but other metabolites can enter at different points in gluconeogenic process . -gluconeogenic precursors include oxaloacetate, pyruvate, lactate, many amino acids -other entering metabolites include glycerol, which comes from hydrolysis of fat reserves- which enters gluconeogenesis at level of g-3-p -but acetly CoA CANNOT act as a gluconeogenic precursor. ..(remember the glyoxylate cycle, which works only in plants, bacteria, to generate glucose (ultimately) from acetyl CoA)
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NET REACTION of gluconeogenesis 2 pyruvate + 4 ATP + 2GTP + 2NADH + 4 HOH > glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+ + 2 H+ The hormones insulin and glucagon regulate blood glucose level. Liver does most of the work by converting glycogen to glucose or, if glycogen depleted by fasting, then gluconeogenesis So, glucose to pyruvate = glycolysis, pyruvate to glucose = gluconeogenesis. Cellular economy dictates that most of the reactions are the same…7 of them, actually.
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2-423-08GluconeoStudent - Gluconeogenesis and The Cori...

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