• Autosomal-recessive deficiency of homogentisic acid oxidase (degradative pathway of tyrosine),
      • benign disease
      • Dark connective tissue, pigmented sclera
      • urine turnes black on standing
      • may have debilitating arthralgias




 Exam MCQ

Which enzyme defect leads to alkaptonuria:

A.  Tyrosine aminotransferase

B.  Homogentisate oxidase

C.  Maleylacetoacetate isomerase

D. Fumarylacetoacetate hydroxylase

ANS: B. Tyrosine transaminase enzyme deficiency leads to type II tyrosinemia, results in the accumulation of excretion of tyrosine metabolites (P-hydroxylphenylpyruvate, P-hydroxyphenyllactate, P-hydroxylphenylacetate etc). Alkaptonuria is due to the defect in homogentisate oxidase. Homogentisate levels are increased and accumulate in tissues and blood and excreted into urine, on oxidation in air, which polymerizes to black colour. Homogentisate is also oxidized to pigments that are deposited in bones, connective tissue and other organs (ochronosis). On oxidation in air, this polymerizes to black colour. Type I tyrosinemia is due to the deficiency of the enzymes fumarylacetoacetatehydrolase. Both fumarylacetoacetate and maleylacetate are accumulated and also act as alkylating agents (DNA alkylation), it is a more serious disorder involving in liver failure, renal tubular dysfunction, rickets and poly neuropathy.


Alkaptonuria a rare genetic disease
Alkaptonuria (black urine disease, black bone disease, or alcaptonuria) is a rare inherited genetic disorder in which the body cannot process the amino acids phenylalanine and tyrosine, which occur in protein. It is caused by a mutation in the HGD gene for the enzyme homogentisate 1,2-dioxygenase (EC; if a person inherits abnormal copies from each parent (it is a recessive condition) the body accumulates an intermediate substance called homogentisic acid in the blood and tissues. Homogentisic acid and its oxidated form alkapton are excreted in the urine, giving it an unusually dark color. The accumulating homogentisic acid causes damage to cartilage (ochronosis, leading to osteoarthritis) and heart valves as well as precipitating as kidney stones and stones in other organs.
Alkaptonuria – Depleted
Our last song from our Aggressive Demonstration EP. Sadly, there will be no more, at least not so soon, because of the problems inside the band.