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27 Cards in this Set
- Front
- Back
The porphin ring is a ______ structure
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- tetrapyrrole
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Heme is type III_________ with a coordinated iron atom
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- protoporphyrin
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What is the difference between uroporhyrin type I & type III?
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- differ in order of substituents on ring D
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A _______ oxidizes spontaneously to a Porphyrin
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- PorphyrinOGEN (intermediates in heme synthesis)
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Which cells synthesize heme?
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- all cells synthesize heme, majority from erythrocyte precursors in bone marrow & liver
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What 3 things is heme used in?
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1) hemoglobin
2) cytochromes 3) catalase / peroxidase |
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First step of heme synthesis: _______ + ______ via ________ --> ________. Where does this reaction occur?
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- succinyl CoA + Glycine
- aminolevulinate synthase (ALA synthase) - ALA - reaction occurs in the mitochondria - this is the regulated step --> product is transported into the cytoplasm |
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In the second step of heme synthesis: two molecules of ______ are condensed by ______ to make ________ (a pyrrole). This product is colorless, but becomes colored on ________. What is special about this enzyme?
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- ALA (delta-aminolevulinate)
- delta-aminolevulinate dehydratase - porphobilinogen - oxidation - zinc containing enzyme so subject to lead poisoning |
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In the third step of heme synthesis, the first part requires 4 molecules of _____ to be condensed by ________. In the second part, ______ assures closure into _______.
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- porphobilinogen
- porphobilinogen deaminase (or uroporphyrinogen synthase) - uroporhyrinogen co-synthase - uroporphyrinogen type III |
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Without uroporphyrinogen co-synthase, what happens?
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- ring closes to make uroporphyrinogen type I --> this can be converted to coproporphyrinogen, but not protoporhyrinogen
- type I will spontaneously oxidize to uroporphyrin type I = conjugated double bond system = colored red-brown --> deposits in skin & leads to photosensitivity |
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In the fourth step of heme synthesis, uroporphyrinogen III is converted to ______ by ________. This molecule re-enters the ______.
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- coproporphyrinogen
- uroporphyrinogen decarboxylase - mitochondria |
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In the fifth step of heme synthesis: coproporphyrinogen III is converted to ________ by _________.
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- protoporphyrinogen III
- coproporphyrinogen decarboxylase |
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After protoporphyrinogen is created, _______ makes ________.
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- protoporphyrinogen oxidase
- protoporphyrin |
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Iron is captured by _____ in protoporphyrin to make ______.
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- ferrochelatase
- heme |
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In the liver: ______ is the key regulated enzyme. ____ is they key feedback regulator, what does it do (4 things)?
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- ALA synthase 1 (ALAS1)
- heme 1) inhibits synthesis of ALAS1 by decreasing stability of mRNA (insulin decreases transcription, steroids increase synthesis) 2) inhibition of ALAS1 transport into the mitochondria 3) allosteric inhibition of ALAS1 by heme in mitochondria 4) drugs up regulate P450s increase heme synthesis |
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In immature erythrocytes: Mature erythrocytes do not contain mito, so they do not synthesize ____. What 4 ways does it differ from liver regulation?
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- heme
1) iron increases translation of ALAS2 (removes inhibitor from mRNA) 2) iron increases ferrochelatase activity 3) erythrocyte-specific TFs act on ALAS2 gene promoter 4) inhibition of ALAS2 transport into mitochondria (heme) |
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What happens in porphyrias (what builds up)? What is therapy?
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- accumulation of toxic intermediates until point of defect
- decrease activity of ALAS (no steroid hormones) - no P450 reactive drugs b/c decrease free heme leading to increased ALAS |
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What step is when you start to get skin photosensitivity?
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- uroporphyrinogen
- everything after this (including this) is insoluble - skin sensitivity to tetrapyrroles |
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What is the best way to diagnose a porphyria? Treatment?
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- urine PBG test
- analysis of excreted: ALA, PBG, uroporphyrinogen (urine), uroporhyrinogen, copro, proto (stool) - decrease ALAS activity, glucose, no P450 drugs |
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Porphyrias are characterized by high levels of __________ (and synthase activity) and by intermediates up to the deficiency (test: urine_____)
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- d-aminolevulinic acid (ALA)
- PBG |
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difference between congenital (hereditary) and acquired porphyria? What tissues are usually affected?
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- congenital shows up
- acquired shows symptoms when confounding factors present - neurological problems |
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Acute intermittent porphyria
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- PBG deaminase deficiency
- porphobilinogen --> porphobilin - urine turns purple |
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Porphyria cutanea tarda
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- uroporphyrinogen decarboxylase deficiency
- uroporphyrinogen --> uroporphyrin III - vampire disease - photosensitive, not soluble |
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Heme is broken down by mixed function oxidase, a _______ enzyme system
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- cytochrome P450
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When heme is broken down it is converted to ______ (green) then converted to ______ (yellow-brown)
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- biliverdin
- bilirubin - accumulation fo bilirubin = jaundice |
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Liver disease: accumulation of________, Excessive hemolysis: accumulation of_______, Occlusion of bile duct: accumulation of ________. Which enzyme conjugates bilirubin?
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- non-conjugated bilirubin
- non-conjugated bilirubin - conjugated-bilirubin - diglucuronyl transferase |
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why do newborns get jaundice? How do you treat?
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- maternal liver normally metabolizes heme produced by fetus
- expression of DUP-glucuronyl transferase occurs after birth - light therapy can help remove bilirubin - make it more soluble and hydrophilic |