urea synthesis

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UREA SYNTHESIS : 

UREA SYNTHESIS Dr.V. SIVA PRABODH MD. NRI MEDICAL COLLEGE

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Metabolism of Ammonia COOH – CHNH2 - CH2 - CH2 - COOH Glutamic acid Glutamine Synthetase NH4+ H2O ATP ADP + Pi COOH – CHNH2 - CH2 - CH2 – CONH2 H2O Glutaminase Mg 2+ NH4+ Glutamine

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AMMONOTELIC : Excrete Ammonia Aquatic animals URICOTELIC: Excrete Uric acid Birds UREOTELIC : Excrete Urea Mammals

UREA SYNTHESIS: : 

UREA SYNTHESIS: UREA CYCLE or KREBS HENSELEIT CYCLE UREA IS SYNTHESISED IN LIVER AND EXCRETED BY KIDNEY. 5 STEPS ARE INVOLED IN UREA SYNTHESIS, 2 STEPS IN MITOCHONDRIA AND 3 STEPS IN CYTOSOL. REQUIRES NH4, CO2 3 ATP(4 high energy high energy phosphates) and ASPARTATE.

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Urea Biosynthesis 1st Step: Synthesis of Carbamoyl Phosphate 2nd Step: Formation of Citrulline 3rd Step: Formation of Argininosuccinate 4th Step: Cleavage of Argininosuccinate 5th Step: Formation of Urea by cleavage of Arginine Occurs in Liver Mitochondria Occurs in cytosol

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CH2NH3+ CH2 CH2 H – C – NH3+ COO-- C = O CH2 - NH CH2 CH2 H – C – NH3+ COO -- COO -- C – NH –– CH CH2 – NH CH2 CH2 COO -- CH2 H – C – NH3+ COO -- C = CH2 – NH CH2 - CH2 H – C – NH3+ COO -- HC – COO- -OOC - CH-` C OO – 2 – C -– H CH2 COO -- Mg – ATP AMP + Mg - PPi O O H2N – C – O – P – O – O–- CO2 NH4+ Co2 + 2Mg - ADP + Pi 2Mg - ATP N – Acetyl - glutamate C = O H2O Carbamoyl phosphate synthase I Ornithine Transcarbomoylase Argininosuccinic acid synthase Arginase Argininosuccinase Carbamoyl phosphate Pi Argininosuccinate L - Asparatate L - Ornithine L - Arginine Fumarate 1 3 4 5 NH4 + 2 H2N NH2 H2N NH NH NH3+ NH NH2 NH2 L- Citrulline Urea cycle

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Ornithine Arginine Citrulline Urea Cycle (-4 ATP) Oxloacetate Malate Fumarate Urea Carbamoyl Phosphate Argino succinate Aspartate TCA Cycle (+12ATP) Fumarate Interrelation between urea and tricarboxylic acid TCA cycle CO2 CO2 CO2 NH4+ +

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Regulation of Urea Cycle Carbomoyl Phosphate Synthase I is the Pacemaker Enzyme of the Urea cycle. Allosteric activator – N- acetyl glutamate ( NAG ) Glutamate N - Acetylglutamate Acetyl CoA CoA NAG Synthase NAG hydrolase Acetate

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Metabolic disorders of Urea Cycle Defect Hyperammonemia type I Hyperammonemia typeII Citrullinemia Arginosuccinic aciduria Hyperargininemia Enzyme involved Carbamoyl phosphate synthase I Ornithine transcarbamoylase Arginosuccinate synthase Arginosuccinase Arginase

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