Flashcards in Iron is neat! Deck (37):
What are hemes used in?
Cyt p450 and hemo/myoglobin
Hemoglobin is made of ______ globular subunits, the iron in the ring is in the ____________ state.
Where does heme synthesis take place?
Phase I in mitochondria, II in cytosol, III in mitochondria
What is the rate limiting step in heme synthesis? What is it catalyzed by?
The rate limiting step is the conversion of glycine and succinyl-CoA to delta-aminolevulinic acid (ALA) by ALA synthase
What does ALA synthase require? What is it inhibited by?
PLP (B6), inhibited by heme and hemin
Acute intermittent porphyria is a problem in the _____________ enzyme and this process is related to __________ synthesis
Porphobilinogen deaminase (porphobilinogen -> hydroxymethylbilane) , hepatic
It is autosomal dominant
Congenital erythropoietic porphyria is an issue with the ___________________ enzyme and it is involved in what system?
Uroporphyrinogen III synthase (hydroxymethylbilane -> uroporphyrinogen III), erythocyte defect
It is autosomal recessive
What is the most common porphyria?
Porphyria cutanea tarda, problems with uroporphyrinogen decarboxylase (uroporphyrinogen III -> coproporhyrinogen III) and it is an issue in both hepatocytes and erythrocytes
It is autosomal dominant
Describe variegate porphyria
It is hepatic, defect in protoporphyrinogen oxidase (protoporphyrinogen IX -> protoporphyrin IX), the penultimate step in heme synth.
It is autosomal dominant
Lead affects what steps in heme synthesis?
1. The last step, ferrochelatase (protoporphyrin IX-> heme)
2. First cytosolic step, ALA dehydratase (2 ALA -> porphobilinogen)
Drug related porphyria affects what step?
The last step, ferrochelatase (protoporphyrin IX -> heme)
What tint are urine and feces in most porphyria?
How often are RBC recycled?
Every 120 days
What does hemoglobin breakdown yield?
Globin -> AA, heme->degraded
Conjugated bilirubin contains bilirubin and what?
UDP glucuronic acid
Jaundice is caused by an abundance of _____________ bound to _________________ in the blood
Bilirubin and albumin
What are the final breakdown products of hemes? Where are they excreted?
Urobilin (yellow color of urine), stercobilin (red-brown color of feces)
During heme breakdown, iron is taken from the ____________ (__+) state to the _______________ (__+) state.
Ferrous, 2, ferric, 3
Heme oxygenase 1 is inducible by Nrf2, which is ubiquitinated and destroyed when not active much like what protein in epithelial architecture?
In the small intestine, microbes concert bilirubin to colorless _____________
What are the three types of jaundice?
Pre-hepatic, intra-hepatic, post-hepatic
CC: Direct and indirect Bilirubin
Unconjugated bilirubin is insoluble in the blood
Conjugated (to glucuronate) bilirubin is soluble
Congenital Erythropoietic porphyria
Results from a deficiency of uroporphyrinogen III cosynthase
Key intermediates are diverted to the nonfunctional uroporphyrinogen I isomer that produces red color in ruin, teeth, premature destruction of erythrocytes and skin sensitivity
Color changes in bruises
Cleanup of the pooling of blood typical of a bruise by macrophages leads to degradation of hemoglobin to heme (red), biliverdin (green), and bilirubin (reddish yellow)
Formation of these degradation products manifests as visible color change of bruise
Due to low level of conjugating enzyme at birth
Exacerbated by premature birth
Pathological jaundice can result from blood group incompatibility or liver dysfunction
Excess unconjugated bilirubin (>15mg/dL) can diffuse into the basal ganglia and cause toxic encephalopathy (kernicterus)
Treat with blue fluorescent lights
UDP-glucuronyl transferase-related disorders
Criggler-Najjar results from deficiency of UDP-glucuronyl transferase
Type 1 - complete absence of gene > sever hyperbilirubinemia that accumulates in the brain and causes kernicterus
Type II - mutation causes partial deficiency (<25% activity) serum bilirubin is <6mg/dL unless fasting, stressed, or boozing
Inflammation of the liver that leads to hepatic dysfunction
Causes increased levels of conjugated and unconjugated bilirubin
Conjugated bilirubin accumulation in the skin and sclera of eyes manifests as yellow coloration
What is the key feature of pre-hepatic jaundice?
Increased production of unconjugated BR but have normal ALT and AST
What are the key findings of intra-hepatic jaundice?
Variable increased in both conj. and unconj. BR, increase in serum ALT AST, conjugated BR in urine
What are the key clinical findings in post hepatic jaundice?
Elevated BR in blood, normal serum AST and ALT, elevated alkaline phosphatase, elevated levels of bile salts, no urobilin and stercobilin
Neonatal jaundice is a type of ________________ jaundice
Neonatal jaundice is a deficiency in _________________
Crigler-Najjar syndrome is a deficiency in what enzyme?
What are some common treatments for UDP-GT disorders?
Blood transfusions (infuse blood not loaded with BR), phototherapy (help with breakdown), heme oxygenase inhibitors (slow down the breakdown process to slow accumulation), oral CaPO4 and CO3 (forms complexes with BR in gut), liver transplant
Which UDP-GT disorder is often benign?
Gilbert syndrome (UDP-GT functions at 25%)
What are some causes of hepatitis?
Hep A, B, c; alcoholic cirrhosis; liver cancer