Biochem post-midterm- mitochondrial function and hepatic detox of monoamines, alcohol, toluene, heme

• A preferentially metabolizes serotonin
• B preferentially metabolizes phentylamine, dopamine

• deficit in 5-HT, NE, and DA in depression
• first gen anti-depressants were MAO inhibitors (too many peripheral adverse events, now only used if resistant to SSRI)

Some individuals with low/no levels of MAO-A are prone to aggression, especially males

• Ex. deprenyl
• similar to phenthylamine and increases brain DA levels (used in PD treatment adjunct to L-dopa)

• caused by MAO inhibitors
• hyperadrenergic state induced by MAO-I and pressor amines (like tyramine, found in cheese, beer, wine, soy sauce)

disulfiram (antabuse) or cyanide

heme deficiency due to excess p450 synthesis, erythropoietin, acute intermitten porphyria or ALA dehydratase deficiency

• increased ROS , supraoxide radical, and NH4. 
• Increased 4,5-dioxocaleric acid (DOVA), which can cause DNA adducts and liver cancer.

Erythropoietin in nuclei activates transcription of ALAS2 gene, ALAS-mRNA synthesis, transferrin receptor gene. 

Iron binds to IRE-BP of ALAS-mRNA, this induces synthesis of ALAS mRNA which is translated to ALAsynthase protein. ALAS involved in heme synthesis in mitochondria, which will bind globin in the cytosol to make hemoglobin.

• Succinyl CoA+ glycine -> Aminolevulinic acid
• In mitochondrial matrix

• ALA -> Coproporphyrinogen III
• in the cytosol

• Coproporphyrinogen III -> HEME
• mitochondrial matrix

• takes place in the liver
• heme toxin oxidized to bilirubin
• bilirubin further detoxified by glucoronidation or albumin

• Biliverdin is water soluble, bilirubin is fat soluble
• Biliverdin excreted by reptiles/birds
• Bilirubin is a neurotoxin to babies

a GSH transferase on hepatocyte surface that traps bilirubin from plasma and helps transport it to the liver where it is glucoronidated . Conjugated bilirubin leaves through the bile.

causes jaundice (buildup of bilirubin)- caused by genetic mutation in activity of glucoronosyl transferase