Catabolism of Tyrosine

• The catabolism of tyrosine involves breaking down the amino acid tyrosine into simpler, usable compounds through a series of biochemical reactions:

1) Tyrosine Aminotransferase (TAT)

• Reaction: Tyrosine is converted into p-hydroxyphenylpyruvate.

• Mechanism: The enzyme tyrosine aminotransferase (TAT) transfers an amino group from tyrosine to alpha-ketoglutarate, resulting in p-hydroxyphenylpyruvate and glutamate.

2) p-Hydroxyphenylpyruvate Dioxygenase (HPPD)

• Reaction: p-Hydroxyphenylpyruvate is converted into homogentisate.

• Mechanism: The enzyme p-hydroxyphenylpyruvate dioxygenase (HPPD) catalyzes this conversion, requiring molecular oxygen.

3) Homogentisate 1,2-Dioxygenase (HGD)

• Reaction: Homogentisate is converted into 4-maleylacetoacetate.

• Mechanism: The enzyme homogentisate 1,2-dioxygenase (HGD) adds oxygen to homogentisate, producing an unstable intermediate that rearranges into 4-maleylacetoacetate.

4) Fumarylacetoacetate Hydrolase (FAH)

• Reaction: 4-Maleylacetoacetate is converted into fumarate and acetoacetate.

• Mechanism: The enzyme fumarylacetoacetate hydrolase (FAH) catalyzes this final step, where fumarate enters the citric acid cycle and acetoacetate is used in ketogenesis.

Metabolic Disorders of Tyrosine Catabolism

• Several inherited disorders result from defects in enzymes involved in tyrosine catabolism, affecting the body's ability to process tyrosine properly:
  

Metabolic Disorders of Tyrosine Catabolism

1) Albinism

• Cause: Defects in the enzyme tyrosinase.

• Symptoms: Reduced or absent melanin production, vision problems, sensitivity to sunlight, and increased skin cancer risk.

• Management: Protective measures against sunlight.

2) Alkaptonuria

• Cause: Deficiency in homogentisate 1,2-dioxygenase (HGD).

• Symptoms: Accumulation of homogentisic acid, dark urine upon air exposure, and ochronosis (bluish-black discoloration of connective tissue).

• Treatment: Symptom management and possibly joint replacement surgery.

3) Tyrosinemia

Type I

• Cause: Deficiency in fumarylacetoacetate hydrolase (FAH).

• Symptoms: Liver and kidney damage.

• Treatment: Specific diet, nitisinone medication, and potentially liver transplantation.

Type II (Richner-Hanhart Syndrome)

• Cause: Deficiency in tyrosine aminotransferase (TAT).

• Symptoms: Corneal ulcers and palmoplantar hyperkeratosis.

• Treatment: Special diet.

Type III (Hawkinsinuria)

• Cause: Deficiency in p-hydroxyphenylpyruvate dioxygenase (HPPD).

• Symptoms: Developmental and intellectual disabilities.

• Treatment: Dietary adjustments and supplementation.