Glycogen intermediary metabolism

The end product of the intermediary metabolism of fatty acids with an uneven number of carbons differs sharply from those formed after the breakdown of the even-chain fatty acids. Whereas glycogen is produced from the fatty acids having an uneven number of carbon atoms, those fatty acids with an even number of carbon atoms have no glycogenic activity, but, with the possible exception of acetic acid, they are all ketogenic and possess no ketolytic activity. 

The 3 10 cells in the liver—particularly the hepatocytes, which make up 90% of the cell mass—are the central location for the body s intermediary metabolism. They are in close contact with the blood, which enters the liver from the portal vein and the hepatic arteries, flows through capillary vessels known as sinusoids, and is collected again in the central veins of the hepatic lobes. Hepatocytes are particularly rich in endoplasmic reticulum, as they carry out intensive protein and lipid synthesis. The cytoplasm contains granules of insoluble glycogen. Between the hepatocytes, there are bile capillaries through which bile components are excreted. 

Of the protein kinases, protein kinase A is the best investigated and characterized (review Francis and Corbin, 1994). The functions of protein kinase A are diverse. Protein kinase A is involved in the regulation of metabolism of glycogen, lipids and sugars. Substrates of protein kinase A may be other protein kinases, as well as enzymes of intermediary metabolism. Protein kinase A is also involved in cAMP-stimulated transcription of genes that have a cAMP-responsive element in their control region (review Montminy, 1997). An increase in cAMP concentration leads to activation of protein kinase A which phosphorylates the transcription factor CREB at Ser 133. CREB only binds to the transcriptional coactivator CBP in the phosphorylated state and stimulates transcription (see Chapter 1.4.4.2). 

UNIT II Intermediary Metabolism Chapter 6 Bioenergetics and Oxidative Phosphorylation 69 Chapter 7 Introduction to Carbohydrates 83 Chapter 8 Glycolysis 89 Chapter 9 Tricarboxylic Acid Cycle 107 Chapter 10 Gluconeogenesis 115 Chapter 11 Glycogen Metabolism 123... 

Some steps in the intermediary metabolism of glycogen and hexoses are shown in Figure 25-9. Each step is enzymatically catalyzed. In some cases, different enzymes are responsible for the forward and reverse reactions. For example, the initial phosphorylation of glucose is mediated by glucokinase, but the reverse reaction depends on glucose-6-phosphatase. 

Pyrimidine nucleotides, in common with purine nucleotides, are required for the synthesis of DNA and RNA. They also participate in intermediary metabolism. For example, pyrimidine nucleotides are involved in the biosynthesis of glycogen (Chapter 15) and of phospholipids... 

Insulin a polypeptide hormone, M, 5,780 (bovine), synthesized in, and secreted by, the B cells of the islets of Langerhans. The first protein primary sequence ever to be elucidated was that of I. (Fig.l) [F. Sanger etal. Biochem. J. 59 (1955) 509-518], I. is the only hormone that decreases the blood glucose concentration. It affects the entire intermediary metabolism, especially of the liver, adipose tissue and muscle. I. increases the permeability of cells to monosaccharides, amino aci and fatty acids, and it accelerates glycolysis, the pentose phosphate cycle, and, in the liver, glycogen synthesis. It promotes the biosynthesis of fatty adds and proteins. These indirect effects on various enzymes and metabolic processes are listed in the tables. 

The intermediary metabolism of carbohydrate is discussed in Chapter 4, to which the reader is referred for details of the enzymatic conversion of hexoses, the formation of glycogen, and the Embden-Meyerhof scheme of glycolysis. Terminal oxidation of carbohydrate is also discussed the oxidation and reactions of pyruvic acid, the monophosphate shunt, and the tricarboxylic acid cycle are illustrated diagrammatically. 

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