Heme synthesis Flashcards
What is needed for ALA synthase?
Vit B6
Deficiency→anemia
Defective ALA dehydratase symptoms
Acute attacks of abdominal pain and neuropathy
Defective PBG deaminase (in liver)
Acute intermittent porphyria: abdominal pain, neurologic dysfunction
Type: hepatic
Defective Protoporphyrinogen IX oxidase
Variegate porphyria: photosensitivity, developmental delay in children
Type: Hepatic
Defective Ferrochelatase
Erythropoietic protoporphyria: Photosensitivity w/ skin lesions after brief sun exposure, gallstones, mild liver dysfunction
Type: erythropoietic
Unconjugated (“indirect”) bilirubin
Hemoglobin is broken down, heme is then turned into unconjugated bilirubin in the spleen. This unconjugated bilirubin is insoluble in water. It is then bound to albumin and sent to the liver.
Conjugated (“direct”) bilirubin
In the liver, bilirubin is conjugated with glucuronic acid by the enzyme glucuronyltransferase, making it soluble in water
Jaundice
Too much bilirubin or not getting rid of it correctly
Pre-hepatic jaundice (hemolytic)
↑ unconjugated bilirubin
- hemolytic anemias
- internal hemorrage
- G6P dehydrogenase deficiency
- Neonatal jaundice due to problem w/ maternal/fetal blood groups (baby’s conjugation enzymes aren’t up and running yet when it’s trying to get rid of fetal Hb)
Symptoms: ↑ unconjugated BR -normal conjugated BR -normal ALT & AST -Urobilinogen present in urine
Intra-hepatic jaundice
-Impaired hepatic uptake, conjugation, or secretion ofconjugated BR
Liver dysfunction
- liver cirrhosis
- viral hepatitis
- Criggler-Najjar syndrom
- Gilbert syndrom
Symptoms:
- ↑ALT/AST
- urobilinogen present in urine
- conjugated BR detected in urine
Post-hepatic
- Problems w/ release
- Cholestasis (decreased bile flow)
Symptoms: ↑ blood conjugated BR w/ much smaller increases in unconjugated form -Normal ALT/AST ↑ ALP ↑ bile salts (b/c preventing release) -Urine is dark -Conjugated BR in urine -No urobilinogen in urine -Pale stool
Neonatal jaundice
- Deficiency of UDP-GT enzyme
- Immature hepatic pathways-unable to conjugate and excrete bilirubin
Treatment: UV light–>breaks down bilirubin
Criggler-Najjar syndrome
Cause: UDP-GT deficiency
Type 1: complete loss of gene
Symptoms:
-severe hyperbilirubinemia (accumulates in brain of affected newborns–>causes kernicturus)
Treatment:
- Phototherapy
- Blood transfusions
- Heme oxygenase inhibitors
- Oral Calcium phosphate
- Liver translation
Type 2: benign form (mutation in gene)
Gilbert Syndrome
Reduced activity of UDP-GT activity. Not as serious as Crigler-Najjar
Serum BR
Hepatitis
Liver inflammation
- Leads to liver dysfunction
- Causes ↑ levels conjugated/unconjugated BR in blood
- Accumulates in skin & sclera of eyes→yellow discoloration, urine is tea colored