Mrs. C.Pushpanjali Lecturer Department of SRM Dental College Ramapuram

C.P 1 CYCLE

KREBS -HENSELEIT CYCLE ORNITHINE CYCLE

UREA is the C.Pend product of catabolism. It is a Non Protein Nitrogenous substance.(NPN) CYCLIC Process where the highly toxic substance is converted to less toxic excretory product UREA. HUMAN-UREOTELIC

C.P Department of Biochemistry 2 IN BLOOD 15-40mg/dL

EXCRETION IN 15-30g/DAY UREA IS SYNTHESISEDS BY LIVER AND EXCRETED BY

C.P Department of Biochemistry 3 IN MITOCHONDRIA Carbamoyl phosphate synthetase I

OrnithineC.P transcarbamoylase IN CYTOSOL Arginosuccinate synthetase Arginosuccinate lyase Arginase

C.P Department of Biochemistry 4 C.P Department of Biochemistry 5 C.P Department of Biochemistry 6 1.FORMATION OF CARBAMOYL PHOSPHATE 2.FORMATION OF CITRULLINE 3.FORMATION OF ARGINOSUCCINATE 4.FORMATION OF ARGININE 5.FORMATION OF UREA

C.P Department of Biochemistry 7 ➢1. AMMONIA AND CO2CONDENSES WITH 2 MOLECULES OF ATP TO FORM CARBAMOYL PHOSPHATE CPSI .

➢IT IS THE RATE LIMITING STEP IN UREA FORMATION.

➢THE POSITIVE EFFECTOR IS N-ACETYL GLUTAMATE(NAG)

C.P Department of Biochemistry 8 2.THE CARBAMOYL GROUP IS TRANSFERRED TO THE NH2 GROUP OF ORNITHINE WHICH LEADS TO THE FORMATION OF CITRULLINE. CITRULLINE LEAVE MITOCHONDRIA AND FURTHER REACTIONS TAKES PLACE IN CYTOSOL. 3.ONE MOLECULE OF ASPARTATE IS ADDED.HYDROLYSIS OF ATP TO AMP,SO TWO HIGH ENERGY PHOSPHATE BONDS ARE UTILISED

4.CLEAVAGE OF ARGINOSUCCINATE TO ARGININE AND FUMARATE. 5.UREA FORMATION AND REGENERATION OF ORNITHINE..

C.P Department of Biochemistry 9 THE UREA CYCLE CONSUMES 4 HIGH ENERGY PHOSPHATE BONDS

C.P Department of Biochemistry 10 C.P Department of Biochemistry 11 BRAIN IS VERY SENSITIVE TO AMMONIA. AMMONIA CROSSES BLOOD BRAIN BARRIER .CNS DYSFUNCTION SYMPTOMS SLURRING OF SPEECH BLURRING OF VISION NAUSEA,VOMITTING CONVULSIONS MENTAL RETARDATION COMA AND DEATH.

C.P Department of Biochemistry 12 1.INCREASED AMMONIA CONCENTRATION ENHANCES AMINATION OF ALPHA KETOGLUTARATE ,AN INTERMEDIATE IN TCA CYCLE TO FORM GLUTAMATE IN BRAIN.THIS DEPLETES ALPHA KETO GLUTARATE OF TCA CYCLE,AFFECTING THE CELLULAR RESPIRATION.THIS LEADS TO DYSFUNCTION OF BRAIN CELLS.

C.P Department of Biochemistry 13 2.GLUTAMINE FORMATION OCCURS IN BRAIN FROM GLUTAMATE BY GLUTAMINE SYNTHASE. DECREASED FORMATION OF GABA ,DUE TO DECREASED GLUTAMATE.

C.P Department of Biochemistry 14 1. Sathyanarayana U., Chakrapani U., Textbook of Biochemistry, 4th Edition, Elsevier, 1999. 2. Pankaja Naik, Essentials of Biochemistry, Jaypee Brothers Medical Publishers, 2012. 3. Vasudevan D.M., Sreekumari S., Kannan Vaidyanathan, Textbook of Biochemistry For Medical Students, 6th Edition, Jaypee Brothers Medical Publishers, 1995. 4. www.google.com

C.P Department of Biochemistry 15