What are the disorders of Phenylalanine or Tyrosine Metabolism in Humans?

Answer 1

Phenylalanine Metabolism in Humans

The metabolism of the aromatic amino acids-phenylalanine and tyrosine in man provides a best example of a gene-controlled, enzyme catalyzed biochemical reaction. In man, phenylalanine is an essential amino acid which must be supplied in the dietary proteins. Once in the body, phenylalanine may follow any of three paths. It may be (1) incorporated into cellular proteins, (2) converted to phenylpyruvic acid, or (3) converted to tyrosine. The conversion of phenylalanine into tyrosine takes place in the presence of phenylalanine hydroxylase enzyme, in the liver cells. Tyrosine is converted in turn to 3-4-dihydroxy phenylalanine (nick-named DOPA) by another enzyme and DOPA serves as a precursor for the hormones adrenaline and noradrenaline and for the black pigment, melanin.

Tyrosine itself serves as a precursor of the hormones thyroxine and triiodothyronine. Excess tyrosine is degraded to carbon dioxide and water by a series of steps which involves the formation of p-hydroxyphenyl pyruvate, 2-5 dihydroxy phenyl pyruvate, homogentisic acid, maleylacetoacetic acid, fumaryl acetoacetic acid and fumaric and acetoacetic acid. Excess phenylalanine is degraded by a series of steps to compounds which include phenylpyruvic acid and phenyl lactic acid.

Genetic disorders of the phenylalanine metabolism and resulted diseases-Five rare diseases in man result from improper functioning of five enzyme systems (i.e., metabolic blocks) involved in the metabolism of phenylalanine, tyrosine and their derivatives. All of these diseases have been found to be due to mutant, autosomal recessive genes in homozygous conditions. These diseases are following:

1.Phenylketonuria-Persons with genotype pp fail to produce enzyme phenylalanine hydroxylase (parahydroxylase) with the result that phenylalanine fails to convert into tyrosine and consequently, the concentration of phenylalanine rises in the blood plasma, cerebrospinal fluid and urine. The urine of phenylketonuric (PKUJ patient contains (in addition to phenylalanine) elevated amounts of phenylpyruvic acid, phenyl lactic acid and other derivatives of phenylalanine. PKU patients have light pigmentation and are physically and mentally retarded. The feeble mindedness in PKU patients is thought to -be due to an impairment of the brain tissues by the phenylpyruvic acid in the cerebro-spinal fluid.

2. Alkaptonuria- The persons with genotype hh fail to produce the enzyme homogentisic acid oxidase which catalyzes the oxidation of homogentisic acid. Therefore, in them, normal oxidation of homogentisic acid into water and carbon dioxide does not occur and large amounts of homogentisic acid are excreted in the urine, which turn black upon exposure to the air. Moreover, the homogentisic acid accumulate in the body and become attached to the collagen of cartilage and other connective tissues, due to which, the ear and sclerae are stained black. Persons with such phenotypic abnormalities are said to have alkaptonuria disease.

3. Tyrosinosis-The recessive gene, t in its homozygous condition, blocks the conversion of p-hydroxyphenylpyruvate into 2, S-dihydroxyphenyl pyruvate. This leads to the accumulation of tyrosine, excesses of which are excreted via the urine. This condition is called tyrosinosis. It is reported in only one human and cause no harmful effect.

4. Goitrous cretinism-The persons with cc genotype fail to produce the enzyme which is required for the conversion of tyrosine into thyroxine and triiodothyronine hormones in their thyroid glands. This condition is called goitrous cretinism which is accompanied by a considerable degree of physical and mental retardation and hypertrophy of thyroid gland.

5. Albinism- The persons with recessive AA genotype lack in the tyrosinase enzyme system which is required for the conversion of 3, 4-dihydroxyphenyl alanine (DOPA) into melanin pigment inside the melanocytes. In an albino patient melanocytes are present in normal numbers in their skin, hairs, iris, etc., but lack in melanin pigment.