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