UNIT V Urea Cycle 2024 - .pptx

B.TECH BIOTECHNOLOGY BT301 PC: BIOCHEMISTRY Dr.A.Ravinder, B.Tech, M.Tech., Ph.D., MBA, PGD in IPR Guest Professor, Centre for Biotechnology, College for Engineering, Science and Technology, JNTUH Hyderabad Unit V: METABOLISM OF PROTEINS AND NUCLEIC ACIDS CATABOLISM Urea Cycle Amino a...

B.TECH BIOTECHNOLOGY BT301 PC: BIOCHEMISTRY Dr.A.Ravinder, B.Tech, M.Tech., Ph.D., MBA, PGD in IPR Guest Professor, Centre for Biotechnology, College for Engineering, Science and Technology, JNTUH Hyderabad Unit V: METABOLISM OF PROTEINS AND NUCLEIC ACIDS CATABOLISM Urea Cycle Amino acids: Glutamine, Tryptophan, Cysteine, Proline Nucleic Acids: Structure of Purines, Pyrimidines, Nucleoside, Nucleotide Degradation of Purines, Pyrimidines, Nucleotides ANABOLISM Amino acids: Glutamine, Tryptophan, Cysteine, Proline Synthesis of Purines and Pyrimidines (De novo and Salvage Pathway) CO5: Analyze various pathways related to Proteins and Nucleic Acids  The Urea Cycle The Urea Cycle (ornithine cycle), occurs in the liver and converts ammonia, a toxic byproduct of amino acid metabolism, into urea, which is then excreted from the body through the urine This cycle is crucial for the detoxification of ammonia and maintaining nitrogen balance in the body The urea cycle consists of five main steps that occur in the mitochondria and cytoplasm of liver cells Mitochondria Cytoplasm 1. Formation of Carbamoyl Phosphate 3. Formation of Argininosuccinat 2. Formation of Citrulline 4. Formation of Arginine 5. Formation of Urea Formation of Carbamoyl Phosphate (Mitochondria) Ammonia (NH₃) combines with bicarbonate (HCO₃⁻) and two ATP molecules to form carbamoyl This phosphate reaction is mediated by Carbamoylphosphate synthetase I (CPS I) 2ATP + HCO3− + NH3 → 2ADP + Pi + carbamoyl-. Formation of Citrulline (Mitochondria) Carbamoyl phosphate reacts with ornithine to form Citrulline Citrulline is then transported from the mitochondria to the cytoplasm mediated by mitochondrial ornithine transporter protein This protein is synthesized Formation of Argininosuccinate (Cytoplasm) Citrulline combines with aspartate (which provides the second nitrogen atom) in an ATP- dependent reaction to form arginino succinate Citrulline + Aspartate + ATP → Argininosuccinate + AMP + Pi Enzyme: Argininosuccinate synthase 4. Formation of Arginine (Cytoplasm) Argininosuccinate is cleaved to form arginine and fumarate (a byproduct that enters the citric acid cycle) Argininosuccinate → Arginine+ Fumarate Enzyme: Argininosuccinate Lyase 5. Formation of Urea (Cytoplasm) Arginine is hydrolyzed to form UREA and ornithine Ornithine is then transported back into the mitochondria to participate in another cycle Enzyme: Arginase What happens when the urea cycle goes wrong? If there is a problem with the urea cycle, then the level of ammonia in the blood will rise, causing hyperammonemia Ammonia is able to cross the barrier between the bloodstream and the brain. Once it enters the brain, it can stop the TCA cycle by depleting one of the metabolites, α-ketoglutarate This means that these brain cells cannot make energy, ultimately leading to their death This eventually will lead to neurological problems,