1. BIOC/DENT/PHCY 230 LECTURE 5

2. glu

3. UREA o synthesised mainly in liver o maintains N in a soluble, non-toxic form o transported in blood to kidney for excretion o allows for the elimination of 2 nitrogens CNH 2 O H2NH2N

4. How does nitrogen enter the urea cycle? O P C O H2NH2N carbamoyl phosphate aspartate

5. Carbamoyl phosphate o synthesised from carbon dioxide and ammonia o ammonia comes from deamination of glutamine and glutamate o energy requiring reaction o catalysed by carbamoyl phosphate synthetase (CPS) CO 2 + NH 3 + 2ATPcarbamoyl- P + 2ADP + P i

6. Aspartate o aspartate is generated by transamination glutamate + oxaloacetate  -KG + aspartate

7. CAC Entry of substrates into the urea cycle

8. 1= CPS 2= ornithine transcarbamoylase 5= arginase Urea cycle

9. CAC Recycling fumarate in the CAC

10. CO 2 + NH 3 + 3ATP + 2H 2 O urea + 2ADP + 2P i +AMP + PP i + fumarate Overall equation for urea cycle o urea synthesis is an energy demanding process o the equivalent of 4 ATP are consumed for each molecule of urea synthesised

11. Regulation of urea cycle Two major points of regulation: o concentration of urea cycle enzymes o CPS activity

12. CPS activity o CPS is allosterically regulated o N-acetylglutamate activates CPS

13. N-acetylglutamate synthase is activated by arginine positive feedback

14. Disorders of urea cycle enzymes: 1=CPS 2= ornithine transcarbamoylase

15. Nitrogen compounds in urine Urea - major nitrogen excretion product. NH 4 + - produced in the kidney by deamination of glutamine. Reduces body acidity because the process removes protons.

16. Uric Acid - the final metabolic product of purine- nucleotide degradation. Creatinine - derived in skeletal muscles, by spontaneous cyclisation of creatine & phosphocreatine.

17. Fates of amino acid carbon skeletons Carbon skeletons can be glucogenic or ketogenic

18. Biosynthesis of amino acids

20. The take home message o urea is a small organic metabolite used to eliminate excess nitrogen from the body o the urea cycle requires a substantial input of energy o CPS is the key regulatory step of the urea cycle o other N compounds are excreted in the urine o carbon skeletons can be recycled or oxidised o availability of carbon skeletons determines dietary requirements for amino acids