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 mammals1.) Biosynthetic pathways of -aminolevulinate

2.) Biosynthesis of heme from -aminolevulinate

Ac: acetylPr: propionyl

Heme serves as a feedback inhibitor!

Porphyrias: group of genetic diseases caused by the accumulationin body fluids, and liver of some porphyrin precursors (becauseof 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 urineStercobilin: 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 reservoirin skeletal muscle it can rapidly regenerate ATP from ADP by creatine kinasereaction.  active contraction andglycolysis ATP synthesis

light activity/rest phosphocreatine synthesisat the expense of ATP

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

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 metabolism2GSH + R–O –O –H GSSG + H2O + R –OH (glutathione peroxidase: contains selenocystein!)

(disulfide bond)

Aromatic amino acids:precursors of manyplant substances

Plant growth hormone

Phe, Tyr ↓tannins, alkaloids (morphine),cinnamate, nutmeg, cloves,vanilla, cayenne pepper, etc.

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 NADPHcytochrome P-450 reductase

NO: important biological messenger● neurotransmission● blood clotting● controling blood pressure