69.
Advanced Enzyme Regulation
Covalent Modification
Phosphorylation:
• Kinases add phosphate
• Phosphatases remove phosphate
Example:
Glycogen phosphorylase regulation
Allosteric Enzymes
• Sigmoid curve
• Cooperativity
Example:
PFK-1
70. Detoxification Mechanisms
Phase I Reactions
• Oxidation
• Reduction
• Hydrolysis
Enzyme:
Cytochrome P450
Phase II Reactions
• Conjugation
• Glucuronidation
• Sulfation
Makes drugs water-soluble
71. Eicosanoids
Derived from:
Arachidonic acid
Types:
• Prostaglandins
• Thromboxanes
• Leukotrienes
Functions:
• Inflammation
• Blood clotting
NSAIDs inhibit:
Cyclooxygenase (COX)
72. Calcium Metabolism
Regulated by:
• Parathyroid hormone (PTH)
• Vitamin D
• Calcitonin
Functions:
• Bone health
• Muscle contraction
• Blood clotting
73. Biochemical Basis of Obesity
Mechanisms:
• Insulin resistance
• Increased lipogenesis
• Inflammatory cytokines
Hormones involved:
• Leptin
• Ghrelin
74. Metabolic Syndrome
Components:
• Central obesity
• Hypertension
• Hyperglycemia
• Dyslipidemia
Risk:
• Type 2 diabetes
• Cardiovascular disease
75. Advanced Clinical Biochemistry Markers
Cardiac Markers:
• Troponin I
• CK-MB
Liver Markers:
• ALT
• AST
• ALP
Kidney Markers:
• Creatinine
• BUN
76. Mitochondrial Disorders
Features:
• Muscle weakness
• Neurological symptoms
• Lactic acidosis
Maternally inherited.
77. Inborn Errors of Metabolism
Examples:
• Galactosemia
• Alkaptonuria
• Homocystinuria
Usually:
• Enzyme deficiencies
• Autosomal recessive
79. Metabolic Integration – Organ-Specific
Metabolism
Different organs have specialized metabolic roles.
1. Liver – Metabolic Hub
Functions:
• Glycogenesis & Glycogenolysis
• Gluconeogenesis
• Ketogenesis
• Urea cycle
• Cholesterol synthesis
• Detoxification
Liver maintains:
• Blood glucose levels
• Lipid balance
• Nitrogen removal
Clinical:
• Liver failure → hypoglycemia, hyperammonemia
2. Muscle Metabolism
Resting state:
• Uses fatty acids
Exercise:
• Uses glycogen
• Anaerobic glycolysis → lactate
Cori Cycle:
Muscle lactate → Liver → Glucose
3. Brain Metabolism
• Uses glucose primarily
• Cannot use fatty acids
• During prolonged fasting → uses ketone bodies
4. Adipose Tissue
• Stores triglycerides
• Releases fatty acids during fasting
Regulated by:
• Insulin (storage)
• Glucagon (lipolysis)
80. Cori Cycle and Glucose-Alanine Cycle
Cori Cycle
Muscle:
Glucose → Lactate
Liver:
Lactate → Glucose
Purpose:
• Prevents lactic acidosis
• Maintains glucose supply
Glucose-Alanine Cycle
Muscle:
Amino acids → Alanine
Liver:
Alanine → Glucose
Removes nitrogen safely.
81. Detailed Urea Cycle
Location:
• Mitochondria & Cytosol of liver
Steps:
1. Ammonia + CO₂ → Carbamoyl phosphate
2. Carbamoyl phosphate + Ornithine → Citrulline
3. Citrulline → Argininosuccinate
4. Argininosuccinate → Arginine
5. Arginine → Urea
Defects:
• Hyperammonemia
• Neurological damage
82. Purine and Pyrimidine Salvage Pathways
Salvage Pathway
Recycles bases to form nucleotides.
Key enzyme:
HGPRT
Deficiency:
Lesch-Nyhan Syndrome
• Self-mutilation
• Hyperuricemia
83. Detailed Signal Transduction
cAMP Pathway
Hormone binds receptor →
Adenylate cyclase activated →
cAMP formed →
Protein kinase A activated →
Phosphorylation of target proteins
IP3-DAG Pathway
Hormone →
Phospholipase C activation →
IP3 releases Ca²⁺ →
DAG activates PKC
84. Insulin Molecular Mechanism
Insulin receptor:
Tyrosine kinase receptor
Mechanism:
• Autophosphorylation
• Activation of IRS proteins
• GLUT-4 translocation
Effect:
• Increased glucose uptake
• Increased glycogen synthesis
85. Advanced Oxidative Phosphorylation
Chemiosmotic Theory
Proposed by:
Peter Mitchell
Concept:
Proton gradient drives ATP synthesis.
Uncouplers
Example:
• 2,4-Dinitrophenol
Effect:
• Heat production
• No ATP generation
