In this article we will discuss about the Interrelationship in the Metabolism of Protein, Fat and Carbohydrate: 1. Necessity for Metabolism of Protein Fat and Carbohydrate 2. Necessity of Glucose for the Brain and Erythrocytes 3. Necessity of Continual Supply of Fuel during Starvation.
Necessity for Metabolism of Protein, Fat and Carbohydrate:
1. Pyruvate i s converted to acetyl-CoA which is the starting material for the synthesis of long-chain fatty acids, and by the reverse process, fatty acids are converted to glucose whereas the pyruvate dehydrogenase reaction is essentially nonreversible which prevents the direct conversion of acetyl-CoA to oxaloacetate via the citric acid cycle, since one molecule of oxaloacetate is required to condense with acetyl-CoA and only one molecule of oxaloacetate is regenerated.
On the basis of similar reasons, there cannot be a net conversion of fatty acids having an even number of carbon atoms to glucose or glycogen.
2. Only the terminal 3-carbon portion of a fatty acid having odd number of carbon atoms is glucogenic, as this portion of the molecule will finally form propionyl-CoA by 3-oxidation.
3. Oxaloacetate is an intermediate both in the citric acid cycle and in the pathway of gluconeogenesis.
4. The glycerol moiety of triacylglycerol can form glucose after activation of glycerol 3-phosphate.
5. Many of the carbon skeletons of the nonessential amino acids can be produced from carbohydrate through the citric acid cycle and transamination. Glucogenic amino acids can also produce carbon skeletons that are precursors or members of the citric acid cycle by the reversal of these processes. They are readily converted to glucose and glycogen by gluconeogenic pathways.
6. The ketogenic amino acids are converted to acetoacetate which is metabolized as ketone bodies forming acetyl-CoA in extra hepatic tissues.
7. It is not possible for a net conversion of fatty acids to carbohydrate and also for a net conversion of fatty acids to glucogenic amino acids.
However, it is possible for the conversion of the carbon skeletons of glucogenic amino acids to fatty acids either by formation of pyruvate and acetyl- CoA or by reversal of non-mitochondrial reactions of the citric acid cycle from α- ketoglutarate to citrate followed by the action of ATP-citrate lyase to give acetyl-CoA.
However, under starvation, a net breakdown of protein and amino acids is accompanied by a net breakdown of fat. The net conversion of amino acids to fat is not a significant process except in animals receiving a high-protein diet.
Necessity of Glucose for the Brain and Erythrocytes:
1. Gluconeogenesis is very important because certain tissues and cells including the central nervous system and the erythrocytes are fully dependent on a continual supply of glucose.
2. A minimal supply of glucose is also necessary for extra-hepatic tissues to maintain oxaloacetate concentrations and the integrity of the citric acid cycle.
3. Glucose is the main source of glycerol 3-phosphate in tissues devoid of glycerol kinase such as adipose tissue.
4. A minimal amount of glucose is a must under all conditions.
5. Large quantities of glucose are essential for fetal nutrition and synthesis of lactose in milk.
6. Certain mechanisms are also involved in supplying glucose in times of shortage by introducing other substrates to spare its oxidation.
Necessity of Continual Supply of Fuel during Starvation:
1. During starvation, glucose availability from food becomes less and liver glycogen is involved in maintaining the blood glucose. The level of insulin in the blood decreases, and glucagon increases.
2. Since the glucose utilization diminishes in adipose tissue and the inhibitory effect of insulin on lipolysis becomes less, fat becomes mobilized as free fatty acids and glycerol. The free fatty acids are oxidized or esterified in the tissues. Glycerol is activated to glycerol 3-phosphate in the liver and kidney.
3. In fasting state, endogenous glucose production (from amino acid and glycerol) does not keep pace with its utilization and oxidation. Therefore, the stores of liver glycogen become depleted and blood glucose level falls.
4. Fat is mobilized rapidly and in several hours the plasma free fatty acids and blood glucose stabilize at the fasting level. At this point, there is the increased oxidation of fatty acids forming ketone bodies.
In case of demands of more glucose, carbohydrate in the form of glycerol in adipose tissue performs an important function, for it is only this source of carbohydrate together with that provided by gluconeogenesis from protein.
5. In prolonged starvation in humans, gluconeogenesis from protein is diminished. This adapts the brain to replace half of the glucose oxidized with ketone bodies.