Download Aminosav metabolizmus IV. Aminosavak bioszintézise

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)
(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