Homogentisic acid degradation

B. PKU is caused by a deficiency of phenylalanine hydroxylase, which converts phenylalanine to tyrosine. A defect in tyrosine degradation causes homogentisic acid to accumulate and produce dark pigments (alcaptonuria). A defect in the conversion of tyrosine to the skin pigment melanin causes albinism. 

Diagram 9. Pathway proposed by Williams and Sreenivasan (929) for formation and further degradation of homogentisic acid. 

Diagram 10. Summary of view.s of Uchida, Suzuki, and Ichihara (878) on homogentisic acid formation and degradation. 

Collective name for polyprenylated 2,3-dimethylben-zoquinone derivatives, [e.g., PQ-9 (n=9), C5jH ,02, Mr 749.22, bright yellow platelets, mp. 48-49 C, u max 314 nm (petroleum ether)], isolated from chloro-plasts. The P. play a role as redox substrates in photosynthesis for cyclic and non-cyclic electron transport where they are converted reversibly into the corresponding hydroquinones (plastoquinols). The biosynthesis of P. proceeds from homogentisic acid, a product of L-tyrosine degradation, through prenylation and methylation (methyl group from L-methionine) to the plastoquinols which are dehydrated to the P.. ... 

L-tyrosine is degraded via 4-hydroxyphenylpyruvic acid and homogentisic acid to acetoacetic acid and fumaric acid (Fig. 267). 

The aromatic nucleus and one of the methyl groups are derived from homo-gentisic acid, a product of L-tyrosine degradation (D 22). Homogentisic acid reacts with prenylpyrophosphates of different chain length (D 6). The quinols formed are reversibly dehydrogenated to the corresponding quinones, e.g.,... 

The oxidation of p-hydroxyphenylpyruvate is a complicated reaction involving several cofactors and two proteins. This reaction results in the formation of homogentisic acid (IV). It is at this step in the degradation... 

A rare inborn (recessive) abnormality of metabolism in man marked by the inability to complete the degradation of tyrosine and phenylalanine their metabolism ceases at homogentisic acid, which is excreted in the urine. The homogentisic acid oxidizes to black melanoid pigment hence, the urine of alcaptonurics slowly turns black. The defect appears to be harmless. 

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