Liver Flashcards
Posthepatic jaundice usually due to what?
Obstruction of the bile duct
Newborn jaundice due to
Low Glucuronyl Transferase activity
Two enzymes of Bilirubin synthesis
Heme Oxygenase
Biliverdin Reductase
High neonatal bilirubin results in
Acute Kernicterus
When would you test for unconjugated bilirubin (indirect)
Hemolytic Anemia and Gilbert syndrome
What is Gilbert syndrome
low glucuronyl transferase
When to test for conjugated bilirubin (direct)
Bile duct obstruction, liver dysfunction,
DUBIN-JOHNSON SYN. (= impaired bile secretion)
What kinds of reactions do CYP enzymes mediate?
They oxidize things to conjugate and excrete (increase solubility. Also: -Expoxidations -N & O dealkylation -S- Oxidation -Hydroxylation
Features of CYP enzymes (3)
Flavin-containing reductase
located on sER membrane
generates radical intermediate
CYP3A4 properties (3)
- most abundant
- inhibited by FURANOCOUMARIN
- metabolize Acetominophen, Cyclosporins, and Lovastatin
Phase 2 detox involves addition of what molecules?
Cysteine, Glycine, + Sulfur, and glucuronide
Sulfation substrates
NT’s
Steroids
Tylenol or other drugs
Glucuronation Substrates
Polycyclic aromatic hydrocarbons
Steroids
Nitrosamines
–Removes used hormones
Substrates for Glycine conjugation
Benzoates and Salicylates
Benzoate is a Tx for what?
Hyperammonemia
What accumulates in porphyria?
ALA + PBG
= heme synthesis intermediates
Porphyrin structure
Cyclic with 4 PYRROLE rings
Binds Iron prosthetic groups for Hb, Mb, and CYP enzymes
2 stages of Heme synthesis (steps and enzymes
- gamma-ALA produced from SUCCINYL-COA and GLYCINE (by ALA Synthase)
- Condensation of 2 gamma-ALA molecules to form PBG (by ALA Dehydratase
gamma ALA synthesis requires what?
B6
Heme synthesis regulation (what inhibits the two enzymes)
ALA synthase inhibited by heme
ALA dehydratase inhibited in LEAD poisioning
**High ALA and low PBG is diagnostic for lead poisoning
Other types of porphyrias (2)
Erythropoietic = low FERROCHELATASE
Porphyria Cutanea Tarda = Most common, low UROPORPHINOGEN DECARBOXYLASE
Tx for Porphyria
Hematin
Iron travels bound to _____, and is stored as _____. Which is used to test for Iron Status?
Transferrin (3+), Ferritin
FERRITIN used to test for iron status
Iron absorption path
Fe2+ absorbed (ferroportin)
Ceruloplasmin conversion to 3+
Excess iron stored as
Hemosiderin
In fatty acid metabolism, flavoprotein transfers what?
electrons to molecular Oxygen
In fatty acid metabolism, FA’s are shortened to ______. Why?
Octanyl CoA - better mitochondrial substrate
MCAD is what? Where?
Medium chain acyl CoA Dehydrogenase
Liver and Kidney
PPAR is…
Peroxisome proliferator- activated receptors
What do PPAR do? (general)
Regulate lipid metabolism by increasing the number of peroxisomes
What is PPAR-alpha? What does it do?
The major receptor in the liver
Binds to FA’s, and signals gene transcription for Lipoprotein lipase, Apolipoprotein A1 & A2, and CPT1
Bile composition
Bile salts + PL’s + Cholesterol + Bilirubin + Water + electrolytes
RLS for bile salt synthesis
7-alpha hydroxylation reaction
Why can’t liver use ketones?
It doesn’t have CoA transferase needed to convert Acetoacetate —-> acetoacetyl CoA
What tissues prefer Ketones?
Cardiac muscle and Kidney
