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29 Cards in this Set
- Front
- Back
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components of heme
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Fe2+ and protoporphyrin IX
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where is most heme synthesized
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in erythroid tissues - Not mature red cells because they have already lost their mitochondria
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formation of aminolevulinic acid (ALA)
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glycine and succinyl-CoA condense to form ALA via ALA synthase
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what two things inhibit ALA synthase and where are they found respectively
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Heme - ALAS1 (liver)
Iron - ALAS2 (erythroid cell) |
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what causes increased synthesis of ALA in the liver
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administration of any drug that results in CYP450 activation and synthesis - CYP450 proteins are composed of a heme group and therefore lower the intracellular heme concentration leading to activation of ALAS1
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porphobilinogen
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condensation of two molecules of ALA via ALA dehydratase
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which two enzymes are zinc-containing and therefore are inhibited by lead
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ALA dehydratase
ferrochelatase |
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how many ALA molecules is one heme group composed of
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8
2 ALA --> porphobilinogen 4 porphobilinogen --> protoporphyrin IX |
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which enzyme enhances the introduction of Fe2+ to protophorphyrin creating heme
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ferrochelatase
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accumulation of what suggests the patient will present with abdominal pain and neuropsychiatric signs
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ALA
porphobilinogen *two molecules prior to tetrapyrrole production |
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accumulation of tetrapyrroles leads to what physical finding
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photosensitivity - itchy and burning skin when exposed to visible sunlight
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what is though to cause the photosensitivity in phorphyria
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formation of superoxide radicals from oxygen
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most common porphyria
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porphyria cutanea tarda
defieincy in uroporphyrinogen decarboxylase leading to accumulation of uroporphyrin |
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what is usually associated with porphyria cutanea tarda (acute hepatic porphyria)
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chronic liver disease
iron overload, alcohol, HBV or HCV |
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what usually precipitates acute hepatic porphyria
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administration of drugs such as barbiturates and ethanol - CYP450 inducers leading to decreased concentration of heme
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which enzyme is deficient in erythropoietic protoporphyria
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ferrochelatase resulting in protoporphyrin IX accumulation
*the increased accumulation of Fe should decrease ALAS2 |
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why is ALA synthase activity increased in all hepatic porphyrias
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decreased production of heme, therefore ALAS1 synthesis is increased leading to over-production of ALA
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treatment of porphyrias
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IV injection of heme and glucose to decrease ALAS1 synthesis
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green pigment seen in bruises
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biliverdin
degraded component of heme before being reduced to bilirubin |
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two disorders associated with decreased conjugation of bilirubin in the liver
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Crigler-Najjar
Gilbert syndrome |
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deficiency in the protein required for transport of conjugated bilirubin out of the liver
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dubin-johnson-syndrome
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two diseases resulting in increased conjugated bilirubin in the blood
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hepatocellular jaundice
obstructive jaundice |
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which enzyme activity is low at birth and results in jaundice
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hepatic bilirubin glucuronyltransferase
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x-linked sideroblastic anemia results in deficiency of which enzyme
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ALA synthase 2
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coenzyme for ALA synthase
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pyridoxal phosphate (PLP)
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enzyme deficiency seen in acute intermittent porphyria resulting in accumulation of porphobilinogen and ALA
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Hydroxymethylbilane synthase - 4 porphobiliogens --> hydroxymethylbilane
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what is diagnostic of porphyria cutanea tarda
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isocoproporphyrin excretion in bile and feces is diagnostic of uroporphyinogen decarboxylase deficiency
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which antibiotic complexes with porphyrins and promotes their excretion
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chloroquine
hydroxychloroquine |
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where can protoporphyrin accumulate in erythropoietic protoporphyria
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1. in the bile and predispose patient to gallstone formation
2. form cystals in liver cells and decrease hepatic blood flow |
