Protein metabolism

1. Protein metabolism

2. Roles of proteins • DNA • Only codes for proteins • Proteins • Structure and shape • Metabolic capability

3. Amino Acids • Building blocks of proteins • 20 in the human body • Contain C,H,O and Nitrogen • Contain • Amine group • NH2 • Carboxyl group • COOH • Also contain a side chain • Makes amino acids different

4. Amino acids • These make up the 20 AAs in the body • Essential • Necessary in the diet • Non-essential • Can be manufactured • Meat vs vegetarian diet

5. Protein structure and function • Proteins • Made up of AAs • Synthesized in the ribosome • Control: DNA & RNA • Chromosomes • Genetic information • Contains codes for protein synthesis • DNA • Pentose sugar (deoxyribose) • Phosphate group • Organic base (purines; A and G and pyrimidines; T and C) • A,T,G,C • Thymine binds Adenine and Cytosine binds guanine • Parallel strands that run in opposite directions

6. Transcription DNA strand unravels Complementary strand of messenger RNA is formed (mRNA) RNA polymerase Uracil (U) replaces T This strand contains a copy of the genetic information coded for on DNA mRNA is translocated from the nucleus to the cytoplasm

7. Translation • mRNA travels to ribsome • Information on mRNA codes for particular proteins • Each amino acid • 3 base pair codon • This is picked up by transfer RNA (tRNA) • tRNA then brings the AA to the developing protein chain

8. Transcriptional and translational control • Transcriptional • Alteration in the concentration of mRNA • Regulation of mRNA polymerase • Translational • Ribosome • Affects the rate at which the protein is synthesized

9. Amino acid metabolism • No excess protein storage in body • Excess is converted to fat or sugar or oxidized • Protein turnover is very high • Repair and maintenance • Enzymes • Rapid turnover allows them to adapt quickly to changing demands • E.g. rise and fall in oxidative enzyme activities with training and detraining • Turnover • Balance between synthesis and degradation

10. Amino Acid metabolism • Transamination • When the amine group of an amino acid is transferred to another molecule • This molecule is typically a keto acid • Essentially an AA without a nitrogen group

11. Deamination • Glutamate dehydrogenase • Along with the coenzyme NAD+ • Deaminates glutamine to alpha-ketoglutarate • Produces ammonia (Glutamate) (Glutamate)

12. Transamination • Serum glutamate-pyruvate transaminase (SGPT) • Transfers nitrogen from Glutamate to pyruvate which is transaminated to alanine (glutamate) (glutamate)

13. Protein metabolism in exercise • Oxidation • Muscle can only oxidize the following AAs • Alanine, aspartate, glutamate, leucine, isoleucine, valine • BCAA • L, I and V • Most important • However, oxidation accounts for only ~ 5-10% of energetic needs

14. Problem with protein metabolism • Nitrogen (specifically, ammonia) • Toxic • Urea cycle • Converts NH3 to urea, which is excreted in the urine • 5 steps 1) Synthesis of carbamoyl phosphate • Requires ATP 2) Formation of citrulline 3) Formation of argininosuccinate 4) Formation of arginine 5) Formation of urea

15. Gluconeogenesis • Some AAs are glucogenic (red), some ketogenic (yellow) • Some also function to help maintain the Kreb’s cycle (anaplerotic additions)

16. Biologically important amino acids • Neurotransmitter AAs • Glycine, glutamate, taurine, aspartate • Neurotransmitter proteins • Acetylcholine • Important to muscle contraction • Synthesis: • Acetyl-CoA and Choline • Choline acetyl transferase • Degradation • Acetylcholinesterase

17. Amino acids • Catecholamines • Epinephrine, Nor-epinephrine • Synthesis • Tyrosine • All the products of this pathway have biological effects • L-DOPA • Used to treat Parkinson’s disease • Precursor to dopamine, nor-epi and epi • Precursor to melanin • Dopamine • Neurotransmitter • Sympathetic nervous system stimulant

18. Amino acids • 5-Hydroxytryptamine (serotonin) • Neurotransmitter • Synthesized from tryptophan • Contributes to well-being • Leads to melatonin • Produced in pineal gland • Important to circadian rhythms • Powerful antioxidant

19. Regulatory peptides and proteins • Metabolic regulators • Insulin • Produced in beta cells (islets of Langerhans) of pancreas • Primarily Anabolic • Glycogen storage • Reduced lipid mobilization • Stimulates protein synthesis • Glucagon • Produced in alpha cells • Primarily “Anti-insulin” • Controlled • Basically by the blood glucose concentration • Somatostatin • Formed in delta cells • Prevents excessive insulin release following a meal

20. Growth factors, gut and brain peptides • Somatomedins • IGF-1 and 2 • Cell proliferation and inhibition of apoptosis • Produced in Liver • Gut peptides • Gastrin • Stimulates secretion of HCl • Released from G cells in stomach, pancreas and duodenum • CCK • Stimulates bile release in response to fat in small intestine • Synthesized in I cells of small intestine • VIP • Increases GI motility • Synthesized in gut, pancreas and hypothalamus • Bombesin (Gastrin releasing peptide) • Stimulates gastrin release • Released from terminals of Vagus nerve • Secretin • Increase water and bicarbonate secretion into the small intestine • Produced by S cells of duodenum • Brain peptides • Endorphins • Endogenous morphine • Produced in brain, released via hypothalamus and pituitary