Catabolism of aromatic amino acids, disorders

Aromatic amino acids, like other proteogenic amino acids, are the building blocks of proteins and include phenylalanine, tryptophan, and tyrosine. All plants and micro-organisms synthesise their own aromatic amino acids to make proteins. However, animals have lost these costly metabolic pathways for aromatic amino acids synthesis and must instead obtain the amino acids through their diet.

1. Phenylalanine and Tyrosine: These two amino acids merge into a common pathway via conversion of Phe to Tyr through hydroxylation. The reaction is catalysed by phenylalanine hydroxylase which requires tetrahydrobiopterin. This pathway leads to formation of fumarate as well as acetoacetate, implying that the two amino acids are both glucogenic and ketogenic.

Note that in this pathway, maleyl acetoacetic acid (cis) and fumaryl acetoacetic acid (trans) are geometric isomers.

Disorders:

Phenylketonuria

Phenylketonuria is caused by a deficiency of phenylalanine hydroxylase. It is characterised by accumulation of phenylalanine (and a deficiency of tyrosine). Hyper phenyl alaninemia may also be caused by deficiencies in any of the several enzymes required to synthesise BH4, or in BH2reductase, which regenerates BH4 from BH2.

a.Elevated phenylalanine: Phenylalanine is present in elevated concentrations in tissues, plasma, and urine. Phenyl lactate, phenyl acetate, and phenylpyruvate, which are not normally produced in significant amounts in the presence of functional phenylalanine hydroxylase, are also elevated in PKU. These metabolites give urine a characteristic musty, odour.

b. CNS symptoms: Mental retardation, failure to walk or talk, seizures, hyperactivity, tremor, microcephaly, and failure to grow.

c. Hypopigmentation: Patients with phenylketonuria often show a deficiency of pigmentation. The hydroxylation of tyrosine by tyrosinase, which is the first step in the formation of the pigment melanin, is competitively inhibited by the high levels of phenylalanine present in PKU.

Albinism

Albinism refers to a group of conditions in which a defect in tyrosine metabolism results in a deficiency in the production of melanin. It causes pigment deficiency and may cause visual impairment, as well as increased susceptibility to skin cancer. The two types are occulocutaneous and ocular.

2. Tryptophan This amino acid is both glucogenic and ketogenic because its catabolism yields alanine and acetoacetyl CoA. Catabolism can lead to formation of niacin, serotonin and auxins Note: Quinolinate from tryptophan catabolism is used in the synthesis of nicotinamide adenine dinucleotide (NAD)

Disorders:

Hartnup disease

Hartnup disease is an autosomal recessive metabolic disorder affecting the absorption of nonpolar amino acids (particularly tryptophan that can be, in turn, converted into serotonin, melatonin, and niacin). The symptoms can manifest early in childhood with photosensitivity, rashes, ataxia, tremors and mental retardation.