Glycogen is the major storage form of carbohydrate in animals and corresponds to starch in plants.It occurs mainly in liver.
The process of biosynthesis of glycogen from glucose is known as glycogenesis. This occurs in all the tissues of the body but the major sites are liver and muscles. A considerable amount is synthesised in kidney also.
Glycogenesis is a very essential process since the excess of glucose is converted and stored up as glycogen which could be utilised at the time of requirement. In the absence of this process the tissues are exposed to excess of glucose immediately after a meal and they are starved of it at other times. The following are the various reactions of glycogenesis.
Glucose is phosphorylated to glucose 6-phosphate, a reaction that is common to the first reaction in the pathway of glycolysis from glucose. This reaction is catalysed by hexokinase in muscle and glucokinase in liver in the presence of ATP.
Glucose 6-phosphate is then reversibly converted to glucose 1-phosphate in a reaction catalysed by enzyme phosphogluco mutase. This process requires Mg2+ and a small amount of glucose 1,6-diphosphate as coenzyme.
The glucose 1-phosphate is then activated by the energy produced by the hydrolysis of uridine triphosphate (UTP) in the presence of uridine diphosphate glucose pyrophophosrylase. This is a key reaction in glycogen biosynthesis.
UDP-glucose is the immediate donor of glucose residues in the reaction catalyzed by glycogen synthase, which promotes the transfer of the glucose residue from UDP-glucose to a nonreducing end of a branched glycogen chain.
When the chain has become long with more than 8 glucose units, a second enzyme, namely branching enzyme amylo 1-4 to 1-6 transglycosylase acts on the glycogen and helps in joining of 1,4 glycogen chain with a similar neighbouring chain to form α 1-6 linkage, thus forming a branching point in the molecule. Glycogen thus formed may be stored in liver, muscles and tissues.
When the blood sugar level falls (Hypoglycemia), glycogen stored in the tissues specially glycogen of liver and muscles may be broken down and this process of breakdown of glycogen is called glycogenolysis.
The following are the various steps of glycogenolysis.
The first step in the breakdown of glycogen is catalyzed by two enzymes which act independently.
The first enzyme, namely glycogen phosphorylase with inorganic phosphate catalyses the cleavage of a terminal a 1-4 bond of glycogen to produce glycogen with one molecule less and a molecule of glucose 1-phosphate. The enzyme glycogen phosphorylase cannot cleave a 1-6 linkage. This is carried out by another enzyme called the debranching enzyme (a 1-6 glucosidase) which hydrolyses these bonds and thus make more a 1-4 linkage accessible to the action of glycogen phosphorylase.
The combined action of glycogen phosphorylase and the debranching enzyme converts glycogen to glucose 1-phosphate.
The glucose 1-phosphate is then reversibly converted to glucose 6-phosphate by the action of the enzyme phosphoglucomutase.
The next reaction namely the conversion of glucose 6-phosphate to glucose takes place in the liver and kidney by the action of the enzyme glucose 6-phosphatase.
Glucose 6-phosphatase removes phosphate group from glucose 6-phosphate enabling the free glucose to diffuse from the cell into the extra cellular spaces including blood. This reaction does not occur in the muscles because muscles lack the enzyme glucose 6-phosphatase.
The synthesis of glucose from non-carbohydrate precursors is known as gluconeogenesis. The major site of gluconeogenesis is liver. It usually occurs when the carbohydrate in the diet is insufficient to meet the demand in the body, with the intake of protein rich diet and at the time of starvation, when tissue proteins are broken down to amino acids.
Gluconeogenesis and glycolysis are opposing metabolic pathways and share a number of enzymes. In glycolysis, glucose is converted to pyruvate and in gluconeogenesis pyruvate is converted to glucose. However gluconeogenesis is not exact reversal of glycolysis.
There are three essentially irrevesible steps in glycolysis which are
In gluconeogenesis these three reactions are bypassed or substituted by the following news ones.
1. The formation of phosphoenol pyruvate begins with the carboxylation of pyruvate at the expense of ATP to form oxalo acetate.
Oxaloacetate is converted to phosphoenolpyruvate by phosphorylation with GTP, accompanied by a simultaneous decarboxylation.
2. Fructose 6-phosphate is formed from fructose 1,6-diphosphate by hydrolysis and the enzyme fructose 1,6-diphosphatase catalyses this reaction.
3. Glucose is formed by hydrolysis of glucose 6-phosphate catalysed by glucose 6-phosphatase.
Amino acids which could be converted to glucose are called glucogenic amino acids. Most of the glucogenic amino acids are converted to the intermediates of citric acid cycle either by transamination or deamination.
Propionate is a major source of glucose in ruminants, and enters the main gluconeogenic pathway via the citric acid cycle after conversion to succinyl CoA.
At the time of starvation glycerol can also undergo gluconeogenesis. When the triglycerides are hydrolysed in the adipose tissue, glycerol is released. Further metabolism of glycerol does not take place in the adipose tissue because of the lack of glycerol kinase necessary to phosphorylate it. Instead, glycerol passes to the liver where it is phosphorylated to glycerol 3-phosphate by the enzyme glycerol kinase.
This pathway connects the triose phosphate stage of glycolysis, because glycerol 3-phosphate is oxidized to dihydroxy acetone phosphate in the presence of NAD+ and glycerol 3-phosphate dehydrogenase.
This dihydroxy acetone phosphate enters gluconeogenesis pathway and gets converted to glucose. Liver and kidney are able to convert glycerol to blood glucose by making use of the above enzymes.
The liver and skeletal muscles exhibit a special metabolic cooperation as far as carbohydrates are concerned by the way of a cycle of conversions known as Cori cycle.
In this cycle liver glycogen may be converted into muscle glycogen and vice versa and the major raw material of this cycle is lactate produced by the active skeletal muscles.
At the time of heavy muscular work or strenuous exercise, O2 supply is inadequate in active muscles but the muscles keep contracting to the maximum. Hence, glycogen stored up in the muscle is converted into lactic acid by glycogenolysis followed by anaerobic glycolysis and thus lactate gets accumulated in the muscle. Muscle tissue lacks the enzyme glucose 6-phosphatase hence it is incapable of synthesizing glucose from lactic acid and the conversion take place only in the liver.
Lactate diffuses out of the muscle and enters the liver through blood. In the liver lactate is oxidised to pyruvate which undergoes the process of gluconeogenesis resulting in the resynthesis of glucose. The glycogen may be once again converted to glucose (glycogenolysis) and may be recycled to the muscle through the blood. The process of gluconeogenesis completes the cycle by converting glucose once again to muscle glycogen.