Research Notes: Protein Metabolism
- (from BioCarta) "Excess amino acids in the body can be used as a source of energy, with their carbon skeleton converted to metabolic intermediates such as acetyl-CoA or intermediates in the Krebs cycle. The metabolic breakdown of amino acids releases nitrogen that must be converted to a relatively non-toxic form and then excreted. In mammals, the nitrogen is converted to urea in the liver through a series of reactions called the urea cycle. The ammonia released through the deamination of amino acids is reacted to produce carbamoyl phosphate, a reaction catalyzed by carbamoyl phosphate synthase. The enzyme ornithine transcarbamoylase is found in mitochondria and converts ornithine into citrulline. Citrulline is exported into the cytoplasm where another nitrogen for urea is acquired from aspartate, followed by the release of fumarate to form the amino acid arginine. Urea is released from arginine by the enzyme arginase, bringing the cycle back around to ornithine.
"The general route of entry for amino acids into the urea cycle is through transamination, the transfer of their amino group to alpha-ketoglutarate to form glutamate. The amino group from glutamate is released by glutamate dehydrogenase to create an ammonium ion. The ammonium ion is used to make carbamoyl phosphate, and ultimately urea through the urea cycle. Different amino acids can enter this pathway by different routes. The transfer of the amino group from aspartate to alpha-ketobutyrate creates oxaloacetate, a Krebs cycle intermediate. Alanine goes through transamination to release pyruvate, which can be used as fuel.
"Genetic defects that completely block the urea cycle are not observed in people, perhaps since such a defect would be fatal. Mutations that reduce the activity of the urea cycle have been observed, with serious affects on mental functioning and other toxities caused by elevated levels of ammonia."
- (from BioCarta) "A significant amount of metabolic energy can come from amino acid metabolism, particularly under conditions of starvation. The metabolism of amino acids occurs through common metabolic intermediates, many of them part of or linked to the Krebs cycle. The intermediates like pyruvate, oxaloacetate, fumarate, succinyl-CoA and alpha-ketobutyrate all can contribute to the net synthesis of glucose through gluconeogenesis. The amino acids that are degraded into these intermediates are called glucogenic. Some amino acids are degraded directly to gluconeogenic intermediates, while others contribute to gluconeogenesis more indirectly, such as through conversion to oxaloacetate through the Krebs cycle. Other common intermediates in amino acid metabolism are acetyl-CoA and acetoacetate. Animals do not have a metabolic pathway to convert these intermediates into glucose. Instead the metabolic fate of acetyl-CoA and acetoacetate is the production of fatty acids or ketone bodies. Amino acids that are metabolized to produce acetyl-CoA and acetoacetate are called ketogenic. Several of the amino acids do not fall cleanly into one group or another, but are both ketogenic and glucogenic. For example, isoleucine metabolism produces both acetyl-CoA, which makes it ketogenic, but it also produces succinyl-CoA, which contributes to glucose production."
