lecture 10

lecture 10 - BIS 103 - Lecture 10 - Gluconeogenesis or...

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BIS 103 - Lecture 10 - Gluconeogenesis or glucose synthesis -pyruvate kinase pyruvate carboxylase, biotin, acetyl-CoA, PEP carboxykinase -fructose-1,6-bisphosphatase I -glucose-6-phosphatase Three key sites in glycolysis that are “irreversible” pyruvate kinase - phosphofructokinase - hexokinase Regulation of gluconeogenesis by fructose-2,6-bisphosphate (F-2,6-BP) Synthesis of glycogen : glycogen synthase Degradation of glycogen : glycogen phosphorylase Reactions to get around the 3 key sites
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Three organizing principles of biosynthesis 1. The first principle is that the pathway taken in the synthesis of a biomolecule is usually different from the pathway taken in its degradation. The two opposing pathways may share many reversible reactions, but there is always at least one enzymatic step that is unique to each pathway. In this lecture we will discuss the biosynthesis of glucose as it is carried out in animals.
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2. The second principle is that corresponding anabolic and catabolic pathways are controlled by different regulatory enzymes. These opposing pathways are regulated in a coordinated, reciprocal manner, so that stimulation of the biosynthetic pathway is accompanied by inhibition of the degradative pathway and vice versa. Biosynthetic pathways are usually regulated at their initial step to prevent accumulation of unwanted intermediates.
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3. The third principle is that energy-requiring biosynthetic processes are coupled to an energy-yielding breakdown of ATP in such a way that the overall process is essentially irreversible in vivo . Thus the total amount of ATP (NADPH) energy used in a given biosynthetic pathway always exceeds the minimum amount of free energy required to convert the precursor into the biosynthetic product. The resulting large negative free energy change for the overall process assures that it will occur even when the concentrations of precursors is relatively low.
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Mammalian cells constantly make glucose directly from simple precursors, such as pyruvate and lactate, and then pass the glucose into the blood where it can be taken, e.g. to the brain or to muscle. The synthetic process for making glucose is called gluco- neogenesis. Gluconeogenesis is defined as the biosynthesis of carbohydrate from three-carbon and four-carbon precursors, generally non-carbohydrate in nature.
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Most animal organs can metabolize a variety of carbon sources to generate their energy needs - triacylglycerols, various sugars, pyruvate, amino acids, etc. However, the brain and central nervous system (CNS) require glucose as the sole or major carbon source. This is also true for the kidney medulla, testes, and erythrocytes. Therefore animal tissues must be able to synthesize glucose from other precursors and also to maintain blood glucose levels within narrow limits - both for proper functioning of the brain and CNS and also to provide glucose for glycogen storage in other tissues.
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Why gluconeogenesis (synthesis of glucose)? Ab. 120 g/day used by brain
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This note was uploaded on 04/19/2008 for the course BIS 103 taught by Professor Abel during the Spring '08 term at UC Davis.

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lecture 10 - BIS 103 - Lecture 10 - Gluconeogenesis or...

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