Carbohydrate in excess of requirements for immediate energy yielding metabolism and formation of glycogen reserves in muscle and liver can readily be used for synthesis of fatty acids, and hence triacylglycerol in both adipose tissue and liver (whence it is exported in very low-density lipoprotein). The rate of lipogenesis in human beings is dependent on the carbohydrate content of the diet and total caloric intake. In Western countries dietary carbohydrates provide ~50% of energy intake. In less-developed countries, carbohydrate may provide 60 to 75% of energy intake. However, the total intake of food is so low that there is little surplus for lipogenesis. A high intake of fat inhibits lipogenesis in adipose tissue and liver. Despite the relatively higher fat intake in Western countries lipogenesis is significant because total caloric intake exceeds energy demand requiring diversion of excess carbohydrate calories to lipogenesis.

Fatty acids (and ketone bodies formed from them) cannot be used for the synthesis of glucose. The reaction of pyruvate dehydrogenase, forming acetyl-CoA, is irreversible, and for every two-carbon unit from acetyl-CoA that enters the citric acid cycle, there is a loss of two carbon atoms as carbon dioxide before oxaloacetate is reformed. This means that acetyl-CoA (and hence any substrates that yield acetyl-CoA) can never be used for gluconeogenesis. The (relatively rare) fatty acids with an odd number of carbon atoms yield propionyl-CoA as the product of the final cycle of β-oxidation. Propionyl-CoA can be a substrate for gluconeogenesis, as can the glycerol released by lipolysis of adipose tissue triacylglycerol reserves.

Most of the amino acids in excess of requirements for protein synthesis (arising from the diet or from tissue protein turnover) yield pyruvate, or four- and five-carbon intermediates of the citric acid cycle . Pyruvate can be carboxylated to oxaloacetate, which is the primary substrate for gluconeogenesis, and the other intermediates of the cycle also result in a net increase in the formation of oxaloacetate, which is then available for gluconeogenesis. These amino acids are classified as glucogenic. Two amino acids (lysine and leucine) yield only acetyl-CoA on oxidation, and hence cannot be used for gluconeogenesis, and four others (phenylalanine, tyrosine, tryptophan, and isoleucine) give rise to both acetyl CoA and intermediates that can be used for gluconeogenesis. Those amino acids that give rise to acetyl-CoA are referred to as ketogenic. With prolonged fasting and starvation amino acids are mobilized from muscle protein to provide substrates for gluconeogenesis, oxidized by the liver to support liver energy demands, and contribute to synthesis of ketone bodies.

مواضيع ذات صلة

Biomedically, Glucose is the Most Important Monosaccharide

Saccharides are Aldehyde or Ketone Derivatives of Polyhydric Alcohols

A Supply of Oxidizable Fuel is Provided in Both The Fed & Fasting States

The Flux Through Metabolic Pathways Must be Regulated In A Concerted Manner

Metabolic Pathways at The Organ & Cellular Level

Pathways To Process The Major Products Of our Diet

Overview of Substrate Metabolism in Fasting & Feasting

The selective permeability of the inner mitochondrial membrane necessitates exchange transporters

Many Poisons Inhibit the Respiratory Chain

The Respiratory Chain Provides Most Of The Energy Captured During Catabolism

Electron Transport Via The Respiratory Chain Creates A Proton Gradient Which Drives The Synthesis of ATP

The Respiratory Chain Oxidizes Reducing Equivalents & Acts as A Proton Pump