Conversion of Amino Acids to Specialized Products
A. Synthesis and Degradation of Melanins
- Precursor Amino Acid: Tyrosine
- Conversion Steps:
- Tyrosine → DOPA → DOPA-quinone
Enzyme: Tyrosinase
Cofactor: Copper (Cu²⁺)
- The further polymerization of DOPA-quinone forms:
- Eumelanin (black-brown pigment)
- Pheomelanin (red-yellow pigment)
- Site of Melanin Synthesis: Melanocytes in the basal layer of epidermis
- Melanocytes produce melanin, but keratinocytes store it.
- Function of Melanin:
- Absorbs UV radiation, protects nuclear DNA from mutation and cancer.
- Regulation:
- MSH (Melanocyte Stimulating Hormone) and ACTH increase melanin synthesis.
- Sunlight stimulates tyrosinase activity → tanning.
- Degradation:
- Melanin is not enzymatically degraded but diluted via keratinocyte turnover.
Pathological Conditions Related to Melanin
- Albinism (Oculocutaneous):
- Deficient Tyrosinase activity → No melanin synthesis.
- Normal melanocyte number, but no pigment.
- Light skin, photophobia, high skin cancer risk.
- Vitiligo:
- Autoimmune destruction of melanocytes.
- Patchy depigmentation, irregular borders.
- Melasma & Freckles:
- Increased melanin production, melanocyte number normal.
- Malignant Melanoma:
- Uncontrolled proliferation of melanocytes.
- Very aggressive, metastasizes early.
B. Synthesis and Secretion of Thyroid Hormones (T3 and T4)
- Precursor Amino Acid: Tyrosine
- Tyrosine residues are part of a protein called → Thyroglobulin.
- Iodide Uptake:
- Iodide (I⁻) transported into thyroid follicular cell via Na⁺/I⁻ cotransporter.
- Oxidation of Iodide to Iodine:
- Enzyme: Thyroid Peroxidase (TPO).
- Iodination of Tyrosine on Thyroglobulin:
- Tyrosine + Iodine → MIT (mono-iodotyrosine)
- Tyrosine + 2 Iodine → DIT (di-iodotyrosine)
- Coupling Reactions:
- DIT + DIT → T4 (Thyroxine)
- MIT + DIT → T3 (Triiodothyronine)
(T3 is more active but T4 is more abundant.)
- Release into Blood:
- Thyroglobulin is proteolyzed → releases T3 and T4.
- Transport in Blood: Bound to Thyroxine-binding globulin (TBG).
- Peripheral Conversion:
- T4 → T3 via 5’-deiodinase in tissues.
Functions of Thyroid Hormones
- Increase basal metabolic rate, heat production.
- Stimulate carbohydrate and fat metabolism.
- Essential for growth and CNS development in infants.
- Increase heart rate and cardiac output.
Pathological Conditions Related to Thyroid Hormones
- Hypothyroidism (Low T3/T4):
- Hashimoto thyroiditis, iodine deficiency.
- Symptoms: weight gain, cold intolerance, fatigue, bradycardia.
- In infants → Cretinism (severe developmental delay).
- Hyperthyroidism (High T3/T4):
- Graves’ disease (autoimmune, TSH-receptor stimulating antibodies).
- Symptoms: weight loss, heat intolerance, tachycardia, anxiety, exophthalmos.
- Goiter:
- Iodine deficiency → low T3/T4 → ↑ TSH → thyroid enlargement.
- Thyroid Peroxidase Inhibition by Drugs:
- Propylthiouracil (PTU) and Methimazole block TPO → ↓ T3/T4 synthesis.