Glycolysis & Gluconeogenesis PDF

Glycolysis & Gluconeogenesis  OVERVIEW OF GLYCOLYSIS The glycolytic pathway is employed by all tissues for the breakdown of glucose to provide energy (in the form of ATP) and intermediates for other metabolic pathways. Glycolysis is at the hub of carbohydrate metabolism because virtual...

Glycolysis & Gluconeogenesis  OVERVIEW OF GLYCOLYSIS The glycolytic pathway is employed by all tissues for the breakdown of glucose to provide energy (in the form of ATP) and intermediates for other metabolic pathways. Glycolysis is at the hub of carbohydrate metabolism because virtually all sugars - whether arising from the diet or from catabolic reactions in the body - can ultimately be converted to glucose Glycolysis is the principal route for carbohydrate metabolism. Glycolysis provides ATP in the absence of oxygen. This is especially important, because this allows skeletal muscle to perform at very high levels of work output when oxygen supply is insufficient, and it allows tissues to survive anoxic episodes. Diseases in which enzymes of glycolysis (eg, pyruvate kinase) are deficient are mainly seen as hemolytic anemias or, if the defect affects skeletal muscle (eg, phosphofructokinase), as fatigue.  TRANSPORT OF GLUCOSE INTO CELLS Glucose cannot diffuse directly into cells, but enters by one of two transport mechanisms: Na+-independent, facilitated diffusion transport system Na+-dependent monosaccharide cotransporter system.  GLYCOLYSIS CAN FUNCTION UNDER ANAEROBIC CONDITIONS Figure 15.3 Glycolysis is a preparatory pathway for aerobic metabolism of glucose. Textbook of Biochemistry with Clinical Correlations, 7e edited by Thomas M. Devlin © 2011 John Wiley & Sons, Inc. Pyruvate is the end product of glycolysis in cells with mitochondria and an adequate supply of oxygen. This series of ten reactions is called aerobic glycolysis because oxygen is required to reoxidize the NADH formed during the oxidation of glyceraldehyde 3-phosphate Aerobic glycolysis sets the stage for the oxidative decarboxylation of pyruvate to acetyl CoA, a major fuel of the TCA (or citric acid) cycle. Alternatively, pyruvate is reduced to lactate as NADH is oxidized to NAD+.This conversion of glucose to lactate is called anaerobic glycolysis because it can occur without the participation of oxygen. Anaerobic glycolysis allows the production of ATP in tissues that lack mitochondria (for example, red blood cells) or in cells deprived of sufficient oxygen. The conversion of glucose to pyruvate occurs in three stages: Phosphorylation state, same as investment phase in which the phosphorylated forms of intermediates are synthesized at the expense of ATP Splitting state: Aldolase and Isomerase reactions Oxido-Reduction state, same as ATP production state. The subsequent reactions of glycolysis constitute an energy generation phase in which a net of two molecules of ATP are formed Figure 15.6 The glycolytic pathway, divided into three stages. Textbook of Biochemistry with Clinical Correlations, 7e edited by Thomas M. Devlin © 2011 John Wiley & Sons, Inc. Lactate formation in muscle: In exercising skeletal muscle, NADH production (by glyceraldehyde 3-phosphate dehydrogenase) is used in conversion of pyruvate to lactate (no oxygen adequate supply). Thus, during intense exercise, lactate accumulates in muscle, causing a drop in the intracellular pH, potentially resulting in cramps. Much of this lactate eventually diffuses into the bloodstream, and can be used by the liver to make glucose GLUCONEOGENESIS (de novo synthesis of Glucose) Figure 15.31 Pathway of gluconeogenesis from lactate. Textbook of Biochemistry with Clinical Correlations, 7e edited by Thomas M. Devlin © 2011 John Wiley & Sons, Inc. Figure 15.34 Reaction catalyzed by glucose 6-phosphatase. Textbook of Biochemistry with Clinical Correlations, 7e edited by Thomas M. Devlin © 2011 John Wiley & Sons, Inc. Diabetes mellitus (type 1, or insulin-dependent diabetes mellitus; IDDM) is characterized by decreased glucose tolerance as a result of decreased secretion of insulin because of progressive destruction of pancreatic beta-islet cells. Glucose tolerance is also impaired in type 2 diabetes mellitus (noninsulin- dependent diabetes, NIDDM) as a result of impaired sensitivity of tissues to insulin action. Insulin resistance associated with obesity (and especially abdominal obesity) leading to the development of hyperlipidemia, then atherosclerosis and coronary heart disease, as well as overt diabetes, is known as the metabolic syndrome.