Q.17 Which of the following enzymes is absent in a person suffering from
Alkaptonuria?
(A) Tyrosinase
(B) Homogentisic acid oxidase
(C) Catechol dioxygenase
(D) Phenylalanine hydroxylase
Homogentisic acid oxidase is absent in Alkaptonuria. This rare genetic disorder results from a deficiency in the enzyme that breaks down homogentisic acid in the tyrosine metabolism pathway. The correct answer is (B).
Question Breakdown
Alkaptonuria causes homogentisic acid buildup, leading to dark urine and ochronosis. The defective enzyme is homogentisate 1,2-dioxygenase, also called homogentisic acid oxidase. This blocks conversion of homogentisic acid to maleylacetoacetate.
Option Analysis
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(A) Tyrosinase: This enzyme catalyzes melanin production from tyrosine in melanocytes. No direct role in homogentisic acid metabolism or Alkaptonuria deficiency, though one hypothesis links it to ochronosis pigmentation.
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(B) Homogentisic acid oxidase: Correct. Also known as homogentisate 1,2-dioxygenase (HGD), its absence causes homogentisic acid accumulation in liver, kidney, and other tissues. Autosomal recessive HGD gene mutations confirm this.
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(C) Catechol dioxygenase: Bacterial or environmental enzyme cleaving catechol rings, analogous to HGD but not involved in human tyrosine catabolism or Alkaptonuria. Absent in standard pathway descriptions.
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(D) Phenylalanine hydroxylase: Converts phenylalanine to tyrosine upstream in the pathway. Its deficiency causes phenylketonuria (PKU), not Alkaptonuria.
Tyrosine Pathway Context
Phenylalanine converts to tyrosine, then to p-hydroxyphenylpyruvate, homogentisic acid, and further via HGD. Blockage at HGD leads to excess homogentisic acid oxidizing into ochronotic pigment, causing arthritis after age 30.
Alkaptonuria enzyme deficiency disrupts tyrosine metabolism, leading to homogentisic acid accumulation and ochronosis. This rare autosomal recessive disorder affects 1 in 100,000–250,000 people, with symptoms like dark urine from birth and joint issues later. Understanding the absent enzyme clarifies its biochemistry for exams like CSIR NET.
Causes of Alkaptonuria Enzyme Deficiency
Mutations in the HGD gene impair homogentisate 1,2-dioxygenase (homogentisic acid oxidase), halting homogentisic acid breakdown to maleylacetoacetate. Excess acid oxidizes to pigment, depositing in cartilage and causing arthropathy. No other enzymes like tyrosinase or phenylalanine hydroxylase are primarily deficient.
Symptoms and Diagnosis
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Urine darkens on standing due to homogentisic acid oxidation.
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Ochronosis: Blue-black pigmentation in ears, sclera after age 30.
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Arthropathy resembling osteoarthritis, heart valve issues.
Diagnosis via urine homogentisic acid test or genetic screening.
Tyrosine Catabolic Pathway Role
Tyrosine → 4-hydroxyphenylpyruvate → homogentisic acid → (HGD) → maleylacetoacetate → fumarylacetoacetate. HGD deficiency blocks this, unlike PKU (phenylalanine hydroxylase defect) or unrelated catechol dioxygenase in microbes.
Management Strategies
No cure; nitisinone reduces homogentisic acid but raises tyrosine, risking side effects. Low-protein diet, vitamin C, pain relief, and joint replacement help. Early detection prevents complications.
This covers Alkaptonuria enzyme deficiency for in-depth study.
