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Biochem Oct oct 17 TOPIC 12 (part 2).ppt

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Department
Biochemistry
Course
Biochemistry 2280A
Professor
Derek Mc Lachlin
Semester
Fall

Description
Overview of energy metabolism Glucose P i ATP P i NADPH Glycogen Glucose-6-phosphate Ribose-5-phosphate UTP NADH NADH Nucleotides ATP ATP + NAD DNA, RNA Proteins Amino acids Pyruvate Lactate Cholesterol NADH Ketone bodies Acetyl-CoA NADPH Membrane lipids ADP + P i O2 NADH, FADH 2 NADH Fatty acids FADH 2 H 2 NAD , FAD Triacylglycerols CO 2 ATP GTP Topic 12 Carbohydrate metabolism Topic 12 learning objectives • Identify the different metabolic fates of glucose-6- phosphate, and how these pathways are related • Explain in general terms how glycogen is synthesized and degraded • State the net reactions of glycolysis and gluconeogenesis (including stoichiometries)** • State the metabolic circumstances under which glycogen synthesis, glycogen degradation, glycolysis, and gluconeogenesis are favoured, without memorizing individual regulators Topic 12 learning objectives (continued) • Describe the purpose of fermentation, identify circumstances under which it is used, and give the products of the two main fermentation pathways • Explain the purposes of the pentose phosphate pathway, and identify the ultimate fates of the carbon atoms that enter this pathway • Explain in general terms how pathways that carry out opposite processes (e.g., glycolysis and gluconeogenesis) can both be energetically favourable Carbohydrate metabolism Glucose Pi ATP P NADPH i Glycogen Glucose-6-phosphate Ribose-5-phosphate UTP NADH NADH Nucleotides ATP ATP NAD + DNA, RNA Pyruvate Lactate 1. Glycogen synthesis and breakdown 2. Glycolysis and fermentation 3. Gluconeogenesis 4. Pentose phosphate pathway Carbohydrate storage as glycogen Glucose-6-phosphate Glucose-1-phosphate Meléndez et al. (1999) Biophys J 77:1327-32 UTP glycogen glycogen synthase phosphorylase UDP + 2 Pi P Glycogen i (Like ATP, UTP can be used as an energy source) Allosteric regulation in skeletal muscle ATP Glucose-6-phosphate activation inhibition Glucose-1-phosphate UTP glycogen glycogen synthase phosphorylase UDP + 2 Pi P Glycogen** i AMP Allosteric regulation in liver Glucose Glucose-6-phosphate allosteric allosteric Glucose-1-phosphate UTP glycogen glycogen synthase phosphorylase UDP + 2 Pi P Glycogen i Neither ATP nor AMP regulate Control by phosphorylation in liver & muscle glycogen kinase glycogen P synthase phosphatase synthase Active Inactive kinase glycogen glycogen P phosphorylase phosphatase phosphorylase Inactive Active • Insulin leads to dephosphorylation in liver & muscle • Glucagon leads to phosphorylation in liver • Epinephrine leads to phosphorylation in liver & muscle Glycogen metabolism: influence of insulin Insulin Insulin Insulin Insulin Blood Insulin Insulin Cell Cellular events resulting in dephosphorylation Glucose-1-phosphate glycogen glycogen synthase phosphorylase Active Inactive Glycogen Glycogen metabolism: influence of insulin Glucagon Glucagon Glucagon Glucagon Blood Glucagon Glucagon Cell Cellular events resulting in phosphorylation Glucose-1-phosphate glycogen glycogen synthase P phosphorylase P Inactive Active Glycogen Glycolysis: net reaction Glucose + 2 ADP + 2 P + 2 NAD + i (Other monosaccharides can also feed into the pathway) 2 Pyruvate + 2 ATP + 2 NADH Oxidation in Useable Electron transport mitochondria energy ΔG values for glycolysis reactions Targets for control of flux Gibbs free energy 1 2 3 4 5 6 7 8 9 10 11 Metabolite(s) • Steps 1, 3 and 10 are targets for control of flux through glycolysis Control of flux through glycolysis Glucose Step 1: hexokinase Glucose-6-phosphate citrate ATP Fructose-6-phosphate Step 3: phosphofructokinase Fructose-1,6-bisphosphate AMP , ADP, Pi Fructose-2,6-bisphosphate (6 steps) Phosphoenolpyruvate Step 10
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