Parents bring in their 3-week-old child fearful that he has ingested a poison. They had delayed disposing one of the child’s diapers, and noted a black discoloration where the urine had collected. Later, they realized that all of the child’s diapers would turn black if stored as waste for a day or so. Knowing that phenol groups can complex to form colors, which of the following amino acid pathways are implicated in this phenomenon?
1.The histidine pathway
2.The leucine,isoleucine and valine pathway
3.The phenylalanine,tyrosine,and hemogentisate pathway
4.The arginine and citrulline pathway (urea cycle)
5.The methionine and homocystine pathway
Solution:
Lack of the enzyme homogentisate oxidase causes the accumulation of homogentisic acid, a metabolite in the pathway of degradation of phenylalanine and tyrosine. Homogentisate, like tyrosine, contains a phenol group. It is excreted in the urine, where it oxidizes and is polymerized to a dark substance upon standing. Under normal conditions, phenylalanine is degraded to tyrosine, which is broken down through a series of steps to fumarate and acetoacetate. The dark pigment melanin is another end product of this pathway. Deficiency of homogentisate oxidase is called alkaptonuria (black urine—203500), a mild disease discovered by Sir Archibald Garrod, the pioneer of biochemical genetics. Garrod’s geneticist colleague, William Bateson, recognized that alkaptonuria, like nearly all enzyme deficiencies, exhibits autosomal recessive inheritance.