Protein Metabolism

1. Protein Metabolism

2. Catabolism Synthesis Amino acids Protein Gut Degradation Deposition Protein turnover

3. Protein synthesis • On-going, semicontinuous activity in all cells but rate varies greatly between tissues

4. Rate of protein synthesis

5. Protein synthesis • On-going, semicontinuous activity in all cells but rate varies greatly between tissues • Rate is regulated by hormones and supply of amino acids and energy • Energetically expensive • requires about 5 ATP per one peptide bond • Accounts for about 20% of whole-body energy expenditure

6. Protein degradation • Also controlled by hormones and energy status • Method to assist in metabolic control • turns off enzymes

7. Protein synthesis and degradation • Synthesis must exceed degradation for net protein deposition or secretion • Changes in deposition can be achieved by different combinations of changes in synthesis and degradation

8. Changes in deposition

9. Catabolism Synthesis Amino acids Protein Gut Degradation Deposition Protein turnover

10. Protein synthesis and degradation • Synthesis must exceed degradation for net protein deposition or secretion • Changes in deposition can be achieved by different combinations of changes in synthesis and degradation • Allows for fine control of protein deposition

11. Protein synthesis and degradation • Other possible reasons for evolution of protein turnover include • Allows post-translational conversion of inactive peptides to active forms (e.g., pepsinogen to pepsin) • Minimizes possible negative consequences of translation errors

12. Protein catabolism • Some net catabolism of body proteins occurs at all times • Expressed as urinary nitrogen excretion • yields urea • Minimal nitrogen excretion is termed endogenous urinary nitrogen (EUN)

13. Urinary nitrogen excretion LIVER Amino acids keto acids NH3 CO2 Urea Blood KIDNEY Urea Urine

14. Protein catabolism • Occurs when • dietary protein exceeds requirements • composition of absorbed amino acids is unbalanced • gluconeogenesis is increased

15. Amino acid metabolism • Biosynthesis of nonessential amino acids • Catabolism • Conversion to glucose or fat • Urea cycle

16. Biosynthesis of nonessential amino acids • Transamination reactions • allow extensive interconversion between nonessential amino acids • requires vitamin B6 as a coenzyme

17. Biosynthesis of nonessential amino acids • Tyrosine • From phenylalanine (PKU; 1 in 15,000) • hydroxylation of phenylalanine • important in adrenaline, noradrenaline, thyroxine and melanin synthesis

18. Biosynthesis of nonessential amino acids • From intermediates of glycolysis • from 3-phosphoglycerate and glycine • serine • phosphatidylserine • from serine • glycine • high demand (10-50x greater than dietary intake) • synthesis of purines, collagen, bile salts and glutathione • cysteine • S from methionine • glutathione

19. Biosynthesis of nonessential amino acids • From intermediates of TCA • From oxaloacetate • aspartate • amino donor in urea synthesis • pyrimidine and purine synthesis • asparagine

20. Biosynthesis of nonessential amino acids • From intermediates of TCA • From α-ketoglutarate • glutamate/glutamine • purine and pyrimidine synthesis • proline • arginine • intermediate in the urea cycle • source of vasodilator, nitric oxide

21. Catabolism • Oxidative deamination • Released NH3 converted to urea • Carbon skeleton can be • oxidized (TCA cycle) • used for glucose synthesis (gluconeogenesis) • used for fat synthesis

22. Ketogenic amino acids • Leucine and isoleucine • converted to acetoacetate or acetyl CoA in liver • fuel for other tissues