OVERVIEW OF CARBOHYDRATES METABOLISM

Carbohydrates are one of the four major organic macromolecule that play various roles in the metabolic processes that occur in the body. The medically important monosaccharides are glucose, fructose & galactose. Sucrose & lactose are important disaccharides while the polysaccharides of significance in carbohydrate metabolism include starch and glycogen.
More complex carbohydrates like the oligosaccharides and polysaccharides need to be converted first into simple sugars before being absorbed in the intestines & eventually utilized by the body. In the process of the bodys utilization of these monosaccharides, primarily glucose, simple molecules are produced as byproducts together with the generation of adenosine triphosphate (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 as well 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 made possible through the different processes in the body that aim to support life. We collectively refer to these processes as metabolism. Metabolism generally proceeds in to directions that should be equilibrium with one another. One direction leas to the breakdown of molecules to be used by the body which we call as catabolism and another leads to the build up of more complex molecules from simpler ones which we term as anabolism. The major pathway of carbohydrate catabolism is the conversion of glucose into pyruvate and/or lactate.--- a process known as glycolysis. The reverse pathway, the conversion mainly of pyruvate to glucose 6 phosphate is a major pathway in carbohydrate biosynthesis.

GLYCOLYSIS
Glycolysis 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 of energy. It involves 11 enzyme dependent reactions. The most important enzymes 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 6 phosphate 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 of aerobic glycolysis using glucose or also fructose and galactose yielding pyruvate creates 4 moles of ATP AND 2 moles of NADH, But the process consumes 2 moles of ATP per mole of hexose. Thus, the net gain is 2 moles of ATP as well as 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.

GLUCONEOGENESIS
The literal meaning of gluconeogenesis is the new formation of glucose. It involves the synthesis of glucose from simpler compounds that are not necessarily carbohydrate in nature. These compounds can include glycerol, the sugar alcohol of either glyceraldehydes or dihydrohyacetone, alpha amino acids, and alpha keto acids. Glucose is the major metabolic fuel of the body which the liver can store in the form of glycogen but in amounts only sufficient to supply the body with glucose for 12-24 hours of fasting. During starvation and prolonged fasting, glycerol produced from the hydrolysis of the bodys main storage form of fats, the triglycerides, as well as alpha keto acids produced from amino acid catabolism can serve as sources of glucose to supply the fuel that the body needs. The central pathway of gluconeogenesis from alpha keto acids is the conversion 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 2 moles of NADH, gluconeogenesis consumes 6 moles of ATP and 2 moles of NADH.

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 the production of ribose 5 phosphate used for nucleotide synthesis, the production of NADPH from NADP for the biosynthesis of fatty acids and steroids, the maintenance of the reduced form of glutathione in RBCs needed for normal hemoglobin function, and the interconversion of pentoses and hexoses.

GLYCOGENESIS
This 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 of glucose 6 phosphate into glucose 1 phosphate by the enzyme phosphoglucomutase. The resultant glucose 1 phosphate, in the presence of uridine triphosphate (UTP), is converted to UDP-glucose. Through the action of the enzyme glycogen synthase, UDP-glucose is broken down into UDP & glucose. The same enzyme adds the released glucose to the glycogen polymer in an alpha 1, 4 linkage. For every glucose molecule incorporated into glycogen in glycogenesis, 1mole of ATP is used to first convert glucose into glucose 6 phosphate and 1 mole of UTP is spent to create UDP glucose. In the glycogen molecule, an alpha 1, 6 branching enzyme, removes some of the linked glucose residues & reattaches them via alpha 1, 6 linkages to come up with the proper branching.

GLYCOGENOLYSIS
This is the lysis or breakdown of glycogen to release glucose to be utilized by the body. It is initiated by the enzyme glycogen phosphorylase. Glycogenesis in the muscles is influenced by the hormone ephinephrine & in the liver by glucagon.

HORMONAL CONTROL
Insulin from the pancreas promotes glycogenesis by activating glycogen synthase and also promotes the entry of glucose into the cells. Thus, its overall effect 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, these hormones have an effect of increasing blood glucose levels. Glucocorticoids promote gluconeogenesis & inhibit glycolysis thus causing increase in blood glucose level. Somatotrophic hormone or growth hormone and thyroid hormones also cause increase in blood glucose levels. SOURCE: Clin. Dx and Mgmt by Lab. Mtds. (JB Henry) Biochemistry Reviewer (PJ Friedman) Biochemistry (A. Lehninger)