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OVERVIEW OF CARBOHYDRATES METABOLISM

Carbohydrates are one of the four major organic macromolecule thatplay various roles in the metabolic processes that occur in the body. Themedically important monosaccharides are glucose, fructose & galactose.

Sucrose & lactose are important disaccharides while the polysaccharides ofsignificance in carbohydrate metabolism include starch and glycogen.

More complex carbohydrates like the oligosaccharides andpolysaccharides need to be converted first into simple sugars before beingabsorbed in the intestines & eventually utilized by the body. In the process of thebodys utilization of these monosaccharides, primarily glucose, simple moleculesare produced as byproducts together with the generation of adenosinetriphosphate (ATP), the so called energy currency of the cell. On the other hand,the body also has the ability to synthesize glucose from simpler molecules aswell as store glucose in a form that the body can make use of when the need

arises. All these things, the utilization of only the immediately needed molecules,the conservation of those that are not, and the building up of new ones are madepossible through the different processes in the body that aim to support life. Wecollectively refer to these processes as metabolism.

Metabolism generally proceeds in to directions that should be equilibriumwith one another. One direction leas to the breakdown of molecules to be usedby the body which we call as catabolism and another leads to the build up ofmore complex molecules from simpler ones which we term as anabolism. Themajor pathway of carbohydrate catabolism is the conversion of glucose intopyruvate and/or lactate.--- a process known as glycolysis. The reverse pathway,

the conversion mainly of pyruvate to glucose 6 phosphate is a major pathway incarbohydrate biosynthesis.

GLYCOLYSISGlycolysis is the main pathway of carbohydrate metabolism in humans. It

is the process by which the body is able to make use of glucose as a source ofenergy. It involves 11 enzyme dependent reactions. The most importantenzymes in the regulation of glycolysis are hexokinase, phosphofructokinase &pyruvate kinase. The enzymes involved in glycolysis are located in the cytosol.The initial step in glycolysis is the conversion of glucose into glucose 6phosphate by either the enzymes hexokinase in the muscles of glucokinase in

the liver. In the process, magnesium acts as a cofactor and ATP is consumed.Glycolysis can occur either aerobically or anaerobically. The overall reaction ofaerobic glycolysis using glucose or also fructose and galactose yielding pyruvatecreates 4 moles of ATP AND 2 moles of NADH, But the process consumes 2moles of ATP per mole of hexose. Thus, the net gain is 2 moles of ATP as wellas 2 moles of NADH. In anaerobic glycolysis, on the other hand, only 2 moles of

ATP and no NADH are produced per mole of hexose.

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GLUCONEOGENESISThe literal meaning of gluconeogenesis is the new formation of glucose.

It involves the synthesis of glucose from simpler compounds that are notnecessarily carbohydrate in nature. These compounds can include glycerol, thesugar alcohol of either glyceraldehydes or dihydrohyacetone, alpha amino acids,

and alpha keto acids. Glucose is the major metabolic fuel of the body which theliver can store in the form of glycogen but in amounts only sufficient to supply thebody with glucose for 12-24 hours of fasting. During starvation and prolongedfasting, glycerol produced from the hydrolysis of the bodys main storage form offats, the triglycerides, as well as alpha keto acids produced from amino acidcatabolism can serve as sources of glucose to supply the fuel that the bodyneeds. The central pathway of gluconeogenesis from alpha keto acids is theconversion of ATP. One mole of GTP has the same energy value as one mole of

ATP. If anaerobic glycolysis, there is a net production of 2 moles of ATP and 2moles of NADH, gluconeogenesis consumes 6 moles of ATP and 2 moles ofNADH.

PENTOSE PHOSPHATE PATHWAY (PPP)This pathway is also known as the Hexose Monophosphate Shunt. The

pentose phosphate pathway takes place in the cytosol. Its functions include theproduction of ribose 5 phosphate used for nucleotide synthesis, the production ofNADPH from NADP for the biosynthesis of fatty acids and steroids, themaintenance of the reduced form of glutathione in RBCs needed for normalhemoglobin function, and the interconversion of pentoses and hexoses.

GLYCOGENESISThis refers to the synthesis of glycogen, a homopolymer of glucose, and

the main storage form of carbohydrate in man. The first step in the conversion ofglucose 6 phosphate into glucose 1 phosphate by the enzymephosphoglucomutase. The resultant glucose 1 phosphate, in the presence ofuridine triphosphate (UTP), is converted to UDP-glucose. Through the action ofthe enzyme glycogen synthase, UDP-glucose is broken down into UDP &glucose. The same enzyme adds the released glucose to the glycogen polymerin an alpha 1, 4 linkage. For every glucose molecule incorporated into glycogenin glycogenesis, 1mole of ATP is used to first convert glucose into glucose 6phosphate and 1 mole of UTP is spent to create UDP glucose. In the glycogenmolecule, an alpha 1, 6 branching enzyme, removes some of the linked glucoseresidues & reattaches them via alpha 1, 6 linkages to come up with the proper

branching.

GLYCOGENOLYSISThis is the lysis or breakdown of glycogen to release glucose to be utilized

by the body. It is initiated by the enzyme glycogen phosphorylase. Glycogenesisin the muscles is influenced by the hormone ephinephrine & in the liver byglucagon.

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HORMONAL CONTROLInsulin from the pancreas promotes glycogenesis by activating glycogen

synthase and also promotes the entry of glucose into the cells. Thus, its overalleffect is the decrease in glucose level in the blood.

Ephinephrine from the adrenal glands and glucagons also from the

pancreas promote glycogenolysis & inhibit glycogenesis. As a result, thesehormones have an effect of increasing blood glucose levels.

Glucocorticoids promote gluconeogenesis & inhibit glycolysis thus causingincrease in blood glucose level.

Somatotrophic hormone or growth hormone and thyroid hormones alsocause increase in blood glucose levels.

SOURCE: Clin. Dx and Mgmt by Lab. Mtds. (JB Henry)Biochemistry Reviewer (PJ Friedman)Biochemistry (A. Lehninger)