BIOCHEMISTRY, BIOMEDICINE & PHARMACEUTICS

Heme Biosynthesis and Regulation Biological Importance of Heme  - Oxygen transport (Hemoglobin) & Storage (Myoglobin) - Electron carrier in Electron Transport Chain  (Cytochromes) - Prosthetic group of various enzyme - Deficiency of the enzyme causes porphyria Biosynthetic Pathway for the Synthesis of Heme  Figure 1: Pathway for Heme Synthesis (Source: NEJM).   Steps of the pathway: 1. Formation of Delta Aminolevulinic Acid (ALA): - catalyzed by enzyme ALA synthase, rate limit step for the biosynthesis of Heme - ALA synthase (ALAS) is a mitochondrial enzyme consisting of two isozymes - ALAS1 is a housekeeping gene present in the cells consisting of mitochondria - ALAS2 is the erythroid form of the ALA synthase - Succinyl CoA and Glycine are the precursors that undergo condensation to form ALA - ALAS require pyridoxal-5-phosphate as a cofactor - The deficiency of ALA synthase causes X-Linked Sideroblastic Anemia  2. Conversion of ALA to Porphobilinogen (...

       Lesch Nyhan Syndrome: Clinical Presentation and Biochemical Diagnosis A 3-year-old child was brought to the hospital with a complaint of self-mutilation. He had a chronic ulcer on the buccal surface of his lips, and self-inflicted trauma by biting his finger. History revealed that severe motor retardation was apparent at the age 6 months old and he has never been able to lift or support his trunk.  The growth chart showed that he has growth retardation. Biochemical analysis was performed which is represented below : Serum Uric acid: 9.0 mg/dL Blood Urea : 32 mg/dL Serum Sodium : 139 mmol/l Potassium: 5.1 mmol/l Calcium 39 mmol/l Total Protein: 70 g/L Albumin: 23 g/L Urinary Uric acid: 160mg/100 ml Urinary Glucose: Absent Urinary Protein: Absent Microscopic urine examination: triphosphate crystals Diagnosis? Provisional Diagnosis : Based on the behavioral pattern of self-mutilation, growth retardation, dystonia, and increased serum and ...