1. Other metabolic pathways Pentose phosphate pathway (phosphogluconate pathway) Produces NADPH and ribose 5-phosphate Glc 6-phosphate + 2NADP + + H 2 O  ribose 5-phos + CO 2 + 2NADPH + 2H + NADPH - used in fatty acid and cholesterol synthesis (found most in mammary gland, adrenal cortex, liver and adipose tissue) Ribose 5-phosphate - used to synthesize nucleic acids (occurs at high rates in growing and regenerating tissues and in tumors)

2. Amino Acid Metabolism - Breakdown Needed to produce amino groups because we cannot use N 2 in air for most biological processes Other metabolic pathways

3. Amino Acid Metabolism - Breakdown Other metabolic pathways Injested protein

4. Amino Acid Metabolism - Breakdown Other metabolic pathways

5. Nitrogen Excretion & Urea Cycle Ammonia is toxic, if not used for synthesis of new AAs or other nitrogenous products - excreted! Ammonia deposited in mitochondria of hepatocytes is converted to urea in the urea cycle

6. Other metabolic pathways Urea Cycle - regulation 1. By flux of nitrogen through cycle - depends on diet lots protein in diet = carbon skeletons used for fuel, lots of urea starvation = breakdown muscle protein for energy, lots of urea All enzymes (CPS-I and 4 in cycle) synthesized at higher rates in starving animals and animals on high protein diets 2. Carbomyl phosphate synthetase I allosterically activated by end product

7. Other metabolic pathways Urea Cycle - genetic defects Patient cannot tolerate protein-rich diet, need small amounts of protein Humans cannot live on a protein-free diet though We are incapable of synthesizing half of the 20 AA, these are essential AAs that must be provided in diet Bacteria & plants can synthesize all 20 AAs must be provided in diet

8. Amino Acid Metabolism - Breakdown pathways Other metabolic pathways

9. Amino Acid Metabolism - Breakdown pathways Enzyme cofactors are important to AA catabolism Tetrahydrofolate - transfers 1-carbon units Other metabolic pathways S-Adenosylmethionine - transfers methyl groups

10. Amino Acid Metabolism - Breakdown pathways Other metabolic pathways Glucogenic AAs (red) - degraded to pyruvate,  -ketoglutarate, succinyl-CoA, fumarate, oxaloacetate Go on to be converted into glc & glycogen Ketogenic AAs (blue) - degraded to acetoacetyl-CoA, acetyl-CoA Go on to yield ketone bodies in liver Some AAs are both - Trp, Phe, Tyr, Ile

11. Amino Acid Metabolism - Breakdown pathways Genetic defects affecting AA catabolism Other metabolic pathways

12. Amino Acid Metabolism - Synthesis of all 20 AAs in bacteria or plants Other metabolic pathways

13. Amino Acid Metabolism Gly is a precursor of porphyrins Porphyrins are part of heme, cytochromes Gly, Met, Arg - synthesis of creatine creatine = energy buffer in skeletal muscle Gly, Glu, Cys - synthesis of glutathione Glutathione = redox buffer Tyr - synthesis of catecholamines (correlate with changes in BP) dopamine (Parkinson’s), epinephrine, norepinephrine Glu - synthesis of neurotransmitter GABA (epilepsy) His - synthesis of histamine vasodialator, allergic response, stimulates acid secretion in stomach Tagamet is an antagonist of histamine Met, Ornithine - synthesis of spermine (+4) & spermidine (+3) packaging of DNA Other metabolic pathways