Leu, Ile, Val α-keto acids acyl-CoA derivatives
Maple syrup urine disease (branched chain ketonuria) is hereditary disease. Decarboxylation of α-keto acid is violated due to a defect of dehydrogenase complex. Amino acids and α-keto acids accumulate in the blood. There is their urinary excretion. It has the smell of maple syrup. The disease is rare. It leads to disruption of brain function and death within one year after birth.
4. Metabolism of dicarboxylic amino acids
Glutamic acid is glycogenic and nonessential amino acid. It participates in the synthesis of glutathione and glutamine. This is one of the few compounds, in addition to glucose, which serve as energy source of the brain tissue.
Glutamine is involved in the ammonia transport, the regulation of acid-base equilibrium, is a source of nitrogen for the synthesis of purine and pyrimidine nucleotides and amino sugars.
Aspartic acid is also glycogenic amino acid. It is involved in the carbohydrates biosynthesis, participates in the urea cycle, in transamination reactions, in the synthesis of carnosine and anserin, purine and pyrimidine nucleotides.
5. Metabolism of diaminomonocarboxylic acids.
The main pathway of arginine metabolism is synthesis of urea. Cleavage of arginine leads to the formation of ornithine. Glutamic acid or proline is formed from it.
Metabolism of histidine is the formation and oxidation of histamine.
The lack of histidine is accompanied by a decrease in hemoglobin concentration. At arginine insufficiency hypospermia occurs.
The lack of lysine in humans causes dizziness, nausea, sensitivity to noise.
6. Metabolism of phenylalanine and tyrosine.
After phenylalanine oxidation tyrosine is formed:
Phenylalanine is an essential amino acid, but tyrosine is semi-essential as it is derived from phenylalanine. Phenylalanine is used mostly on protein synthesis and is converted into tyrosine under the action of phenylalanine hydroxylase. Fumarate and acetoacetate are formed from phenylalanine and tyrosine in a series of reactions. The intermediated product is homogentisic acid.
Homogentisic acid is excreted in urine in large amount in congenital absence of the homogentisate oxidase in the liver and kidneys. It is oxidized by atmospheric oxygen and gives the urine a dark color. In severe cases, pigment deposition in tissues occurs and darkening of the nose, ears and sclera develop. The disease is called alkaptonuria. It is not the dangerous disorder. But the diet with low content of phenylalanine is recommended.
There is a hereditary defect that manifests in the synthesis of inactive forms of the enzyme phenylalanine hydroxylase. The concentration of phenylalanine in the tissues of the patient increases tenfold. Much of it turns into a phenylpyruvate and phenyllactate. They are excreted in urine of a patient. Phenylketonuria is the most common metabolic disorder in amino acid metabolism.
There is mental retardation, disturbance of physical development, probably due to the toxic effect of phenylalanine high concentrations. The diet with low content of phenylalanine is necessary, especially at an early age.
In the adrenal medulla and in the nervous tissue tyrosine is a precursor of catecholamines, the most important of which are dopamine, norepinephrine (noradrenaline) and epinephrine (adrenaline).
Adrenaline is the hormone of the adrenal medulla. It stimulates the mobilization of deposited carbohydrates and fats. Dopamine and noradrenaline are neurotransmitters in the conduction of nerve impulses.
Tyrosine is the precursor of melanin pigment formed by the enzyme tyrosinase in pigment cells (melanocytes). Melanin is a group of polymeric compounds with the disordered structure. Congenital absence of tyrosinase in melanocytes or absence of melanocytes is manifested as albinism. This disease is characterized by the absence of skin and hair pigmentation, photophobia.