Figures: Lehninger-4ed; chapter: 22 (Stryer-5ed; chapter: 24) Amino acid metabolism IV. Synthesis of biologically active molecules from amino acids Figures: Lehninger-4ed; chapter: 22 (Stryer-5ed; chapter: 24)

Glycine: precursor of porphyrins in mammals 1.) Biosynthetic pathways of -aminolevulinate

2.) Biosynthesis of heme from -aminolevulinate Ac: acetyl Pr: propionyl

Heme serves as a feedback inhibitor!

Porphyrias: group of genetic diseases caused by the accumulation in body fluids, and liver of some porphyrin precursors (because of the defect of certain enzyme in the biosynthesis of porphyrin). ● buildup of -aminolevulinate and porphobilinogen (acute intermittent porphyria)  - acute abdominal pain - neurological disfunctions (apparent madness) ● accumulation of uroporphyrinogen (rare)  - red urine, the teeth fluoresce in UV light - very sensitive skin to sunlight - anemia (insufficient heme)  vampire miths?

3.) Heme as the source of bile pigments (heme released from dying erythrocytes in the spleen is degraded) Fe2+ binds to ferritin, CO (poison) binds to hemoglobin (1%)

Breakdown of bilirubin (M = methyl, V = vinyl, Pr = propionyl, E = ethyl groups)

Hemoglobin released from damaged erythrocytes: black/purple  Biliverdin: green Bilirubin: yellow Urobilin: gives the yellow colour to the urine Stercobilin: gives the red-brown colour to feces Jaundice: yellow skin and eyeballs (due to impaired liver function or blocked bile secretion  bilirubin leaks into the blood) Jaundice in newborn infants: not enough glucuronyl bilirubin transferase (exposure to fluorescent lamp  photochemical conversion of bilirubin)

These pathways of heme degradation: ● protect cells from oxidative damage ● regulate certain cellular functions CO produced by HO: ● toxic (high conc.) ● vasodilator as NO (low conc.) ● regulatory effects on neurotransmission (low conc.) Bilirubin: ● the most abundant antioxidant in mammalian tissues (antioxidant activity in serum) ● protective effect in developing brain of the newborns

Gly and Arg: precursors of creatine

Phosphocreatine is an important energy reservoir in skeletal muscle  it can rapidly regenerate ATP from ADP by creatine kinase reaction.   active contraction and glycolysis  ATP synthesis light activity/rest  phosphocreatine synthesis at the expense of ATP

Gly, Glu and Cys: precursors of glutathione (GSH)

2GSH + R–O –O –H  GSSG + H2O + R –OH (disulfide bond) GSH (redox buffer): ● maintain the -SH groups of proteins in the reduced form ● the iron of heme in ferrous state (Fe2+) ● serves as reducing agent for glutaredoxin (deoxyribonucleotide synth.) ●removes toxic peroxides formed during growth and aerobic metabolism 2GSH + R–O –O –H  GSSG + H2O + R –OH (glutathione peroxidase: contains selenocystein!)

Aromatic amino acids: precursors of many plant substances Phe, Tyr ↓ tannins, alkaloids (morphine), cinnamate, nutmeg, cloves, vanilla, cayenne pepper, etc. Plant growth hormone

Biosynthesis of some neurotransmitters from amino acids 1.) Tyr is a precursor of catecholamines: • Dopa • Dopamine • Norepinephrine • Epinephrine Levels of catecholamines are correlated with changes in blood pressure!

Parkinson’s disease: underproduction of dopamine (treatment: L- dopa) Schizophrenia: overproduction of dopamine

2.) Glu is a precursor of: GABA (inhibitory neurotransmitter) Epileptic seizures: underproduction of GABA GABA analogs: treatment of epilepsy and hypertension

3.) His is a precursor of: Histamine (powerful vasodilator in animal tissues) Histamine: ● released as part of the allergic response ● stimulates acid secretion in the stomach

4.) Trp is a precursor of: Serotonin (imp. neurotransmitter)

5.) Met is a precursor of: spermine and spermidine (polyamines involved in DNA packaging)

Biosynthesis of nitric oxide (NO) from Arg (nitric oxide synthase reaction) NO synthase : dimeric enzyme, structurally related to NADPH cytochrome P-450 reductase NO: important biological messenger ● neurotransmission ● blood clotting ● controling blood pressure