* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Lehninger Principles of Biochemistry
Survey
Document related concepts
Mitogen-activated protein kinase wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Butyric acid wikipedia , lookup
Proteolysis wikipedia , lookup
Basal metabolic rate wikipedia , lookup
Evolution of metal ions in biological systems wikipedia , lookup
Lipid signaling wikipedia , lookup
Biosynthesis wikipedia , lookup
Oxidative phosphorylation wikipedia , lookup
Adenosine triphosphate wikipedia , lookup
Fatty acid synthesis wikipedia , lookup
Amino acid synthesis wikipedia , lookup
Glyceroneogenesis wikipedia , lookup
Blood sugar level wikipedia , lookup
Fatty acid metabolism wikipedia , lookup
Citric acid cycle wikipedia , lookup
Transcript
David L. Nelson and Michael M. Cox LEHNINGER PRINCIPLES OF BIOCHEMISTRY Sixth Edition CHAPTER 15 Principles of Metabolic Regulation © 2013 W. H. Freeman and Company Factors affecting the activity of enzymes Regulation by reversible phosphorylation A typical ATP-utilizing enzyme has a Km for ATP of about 5 mM The concentration of ATP in animal tissues is about 5 mM Control of glycogen synthesis from blood glucose Hexokinase I of muscle has a low Km for glucose Hexokinase IV of liver has a high Km for glucose Regulation of phosphofructokinase-1 (PFK-1) Reciprocal Regulation of PFK-1 and FBPase-1 Activated by Fructose 2,6-bisphosphate Inhibited by Fructose 2,6-bisphosphate Glucagon, a pancreatic hormone, signals low blood sugar and lowers the level of fructose 2,6-bisphosphate in the liver. This stimulates gluconeogenesis and the production of glucose. Fructose 2,6-bisphosphate is synthesized by the enzyme phosphofructokinase-2 (PFK-2) and broken down by fructose 2,6 bisphosphatase (FBPase-2) Phosphofructokinase-2 (PFK-2) and fructose 2,6 bisphosphatase (FBPase-2) are on the same polypeptide chain and regulated by glucagon Regulation of Pyruvate Kinase Pyruvate kinase is inhibited by: ATP acetyl-CoA long-chain fatty acids High concentrations of ATP signals that glycolysis is not needed for further production of ATP. Acetyl-CoA and fatty acids are fuels for the citric acid cycle. When there is plenty of fuel for the citric acid cycle glycolysis is not needed to provide acetyl-CoA for the citric acid cycle. Regulation of Pyruvate Kinase Glycogen Metabolism Glycogen phosphorylase degrades glycogen Hydrolysis of glucose 6-phosphate occurs in the ER UDP-glucose, synthesized from glucose 1-phosphate, is the glucose donor for glycogen synthesis Branch synthesis in glycogen Why is glycogen branched? 1. Make the glycogen molecule more soluble. 2. Increase the number of reducing ends, the ends where glycogen synthase adds more glucose residues and where glycogen phosphorylase removes glucose residues. Glycogenin primes the initial sugar residues in glycogen The initial glucose monomer (from UDP-glucose) is covalently attached to a tyrosine residue on glycogenin Regulation of glycogen phosphorylase Activated by glucagon Glucose binds to an allosteric site on glycogen phosphorylase a and induces a conformational change that exposes the phosphorylated serines to phosphorylase a phosphatase. The result is a decrease in glycogen breakdown in response to high blood glucose levels. Regulation of glycogen synthase Insulin promotes activation of glycogen synthase and blocks inactivation of glycogen synthase Glucagon blocks activation of glycogen synthase