Other metabolic pathways

Pentose phosphate pathway (phosphogluconate pathway)Produces NADPH and ribose 5-phosphate

Glc 6-phosphate + 2NADP+ + H2O ribose 5-phos + CO2 + 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)

Amino Acid Metabolism - BreakdownNeeded to produce amino groups because we cannot use N2 in air for most biological processes

Other metabolic pathways

Amino Acid Metabolism - Breakdown

Other metabolic pathways

Injested protein

Amino Acid Metabolism - Breakdown

Other metabolic pathways

Other metabolic pathways

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

Other metabolic pathwaysUrea Cycle - regulation1. 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

Other metabolic pathwaysUrea Cycle - genetic defectsPatient cannot tolerate protein-rich diet, need small amounts of protein

Humans cannot live on a protein-free diet thoughWe 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

Amino Acid Metabolism - Breakdown pathways

Other metabolic pathways

Amino Acid Metabolism - Breakdown pathwaysEnzyme cofactors are important to AA catabolism

Tetrahydrofolate - transfers 1-carbon units

Other metabolic pathways

S-Adenosylmethionine - transfers methyl groups

Amino Acid Metabolism - Breakdown pathways

Other metabolic pathways

Glucogenic AAs (red) - degraded to pyruvate, -ketoglutarate, succinyl-CoA, fumarate, oxaloacetateGo on to be converted into glc & glycogen

Ketogenic AAs (blue) - degraded to acetoacetyl-CoA, acetyl-CoAGo on to yield ketone bodies in liver

Some AAs are both - Trp, Phe, Tyr, Ile

Amino Acid Metabolism - Breakdown pathwaysGenetic defects affecting AA catabolism

Other metabolic pathways

Amino Acid Metabolism - Synthesis of all 20 AAs in bacteria or plants

Other metabolic pathways

Amino Acid Metabolism

Gly is a precursor of porphyrinsPorphyrins are part of heme, cytochromes

Gly, Met, Arg - synthesis of creatinecreatine = energy buffer in skeletal muscle

Gly, Glu, Cys - synthesis of glutathioneGlutathione = redox buffer

Tyr - synthesis of catecholamines (correlate with changes in BP)dopamine (Parkinson’s), epinephrine, norepinephrine

Glu - synthesis of neurotransmitterGABA (epilepsy)

His - synthesis of histaminevasodialator, allergic response, stimulates acid secretion in stomachTagamet is an antagonist of histamine

Met, Ornithine - synthesis of spermine (+4) & spermidine (+3)packaging of DNA

Other metabolic pathways