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Unformatted text preview: B iochemis ry E duca ion Department of iochemistry & Molecular iology University of New Mexico BIOC 423 Int oducto y Biochemist y Gluconeogenesis OBJECTIVES Know the role of gluconeogenesis in normal physiological processes. Understand how the "irreversible steps" of glycolysis are by-passed during gluconeogenesis Know the energy requirement of glyconeogenesis and how it is satisfied. Know how glycolysis and gluconeogenesis are reciprocally regulated. Be able to outline the Cori cycle and explain its biological significance. OUTLINE Review the Regulation of glycolysis When is it necessary to synthesize glucose Source of carbon for glucose synthesis Source of energy for glucose synthesis Reversing the "Irreversible Steps" of Glycolysis Pyruvate carboxylase and PEP-carboxy kinase Fructose bis-phosphatase Glucose 6-phosphatase Regulation of gluconeogenesis Cori Cycle Glucose synthesis in anaerobic exercise What can go wrong Diabetes Hypoglycemia LECTURE It is always somewhat problematic to decide where to discuss gluconeogenesis. The word means generation of new glucose or glucose synthesis out of non glucose precursor molecules. Given this definition the synthesis of glucose starting with glycogen is NOT considered gluconeogenesis. Nevertheless, glycogenolysis (breakdown of glycogen) is an important source of glucose that we will review shortly. In this lecture we are going to focus on the synthesis of glucose from non-sugar precursors. Although, it would seem logical to discuss glucose synthesis in the context of the synthesis of other macromolecules, glucose synthesis is different from the synthesis of other macromolecules, in that it uses primarily the reactions of glycolysis. Moreover, gluconeogenesis is very much a part of energy metabolism and the storage and sharing of energy molecules between different tissues. We have already studied most of the glucose synthetic pathway (glycolysis) and we really have only three problematic and irreversible steps to cover in todays lecture. Once we get around these three irreversible steps, gluconeogenesis is simply the reverse of glycolysis. The required questions of new metabolic pathways: Why: The question of why gluconeogenesis is important relates primarily to two different tissues. Recall that glucose is a form of energy that can be freely shared between all tissues and all tissues can use glucose in glycolysis to fuel ATP production. Most tissues are not particularly finicky eaters however and will also accept fatty acid, nucleic acid, and amino acid as fuel molecules. There are three important exceptions. For brain, red blood cell, and lens of the eye, glucose is the primary fuel of choice and for RBC and Lens it is the only acceptable fuel molecule. It has been estimated that brain consumes approximately 80% of the glucose molecules. Without a continual supply of glucose, brain, RBC and lens metabolism stops....
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- Spring '08
- molecular biology