Important enzymes of Heme Synthesis
A-ALA dehydratase
B-porphobilinogen deaminase
C-uroporphyrinogen III synthase (and cosynthase)
D-uroporphyrinogen decarboxylase
Synthesis of Heme
- Important in RBC, hemoglobin, myoglobin, and cytochromes
* Porphyrins are synthesized from glycine and succinyl CoA (rate determining step)** Required B6*
Genetic or environmental defects in enzymes lead to _______.
- Porphyrias, such as lead or agent orange poisoning, photosensitifity (Dracula)
- ALA dehydratase dectefcs - lead poisoning
- Porphobilinogen deaminase defects - acute intermittent porphyria, hepatic, liver effected
- Uroporphyrinogen III synthase defects - congenital erythropoetic prophyria, RBC effected
Heme breakdown
- Heme degradation products (biliverdin and bilirubin) responsible for the color of bruises
- RES enzymes begin this process to convert heme to these
- 2 sugars on bilirubin, secreted on bile, goes to the gut, microorganisms modify this, from there convert to urobilinagin
Two fates of urobilinagin
- Reabsorb in blood, goes to kidney, urinated out, oxidized to urobilin, yellow color
- Rest enzymatically changed to stercobilinogen, oxidized to stercobilin, brownness of feces
Bilirubin
- reddish color, hydrophobic, carried in the blood by albumin
- indirect billirubin, carried to liver where it is modified
- Can cause severe brain damage if to much build up
Sphingosine
- Precursor to membrane lipids
* Derived from Serine*
Histamine is derived from?
•Histidine*
Thyroxine is derived from?
•Thyrosine*
Epinephrine is derived from?
•Thyrosine*
Serotonin is derived from?
•Tryptophan*
Nicotinamide (unit of NAD+) is derived from?
•Tryptophan*
Nitric Oxide is generated from?
- Arginine
* Relaxes smooth muscle, made in endothelium, pass through membranes very rapidly
One of the mechanisms of destruction of NO is?
- macrophages
* NO combined with superoxide to make peroxinitrit (ONOO), very destructive, killa!
NO is used as what?
- Nervous tissue produces NO
- Signal molecule/neurotransmission
- Excitotoxicity, excessive stimulation of one side of the brain, to much makes pathogenic
ENOS, INOS, and NNOS stand for?
- ENOS = endothelium NO synthase
- INOS = Ineducable NO synthase in macrophages
- NNOS = Nervous tissue
Glutathione system
- Serves as an antioxidant, reacting with hydrogen peroxide and organic peroxides
- Cyto protection, enzyme that used glutathione to get rid of peroxide has specific chemical call selenium
