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24 Cards in this Set
- Front
- Back
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describe porphyrins |
organic ring molecules, cofactors for proteins and enzymes tetrapyrroles: bind metals in center colored (blood, bile, urine, feces) |
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what are the major functions of porphyrins |
oxygen transport: hemo/myoglobin electron transport, respiration: cytochrome (c, b, a-a3) redox reactions: cytochrome p450 (detox), catalase (peroxide destruction), cytochrome b5 (stearoyl CoA desaturase) other reactions: nitric oxide synthase |
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describe the spectra of heme proteins |
absorb strongly in visible light spectra vary with redox state (Fe 2 or 3) or ligand (O2 or CO, nitric oxide) some are photosensitizers-- generate toxic delta oxygen in porphyrias when skin is exposed to light some are fluorescent (clinically important with lead poisoning) Fe, Pb don't |
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describe generally the mechanism of creating a porphyrin |
aminolevulinic acid, stick together and make porphobilinogen wrap them around and make tetrapyrrole fuse ring change outer groups put metal ion in the middle |
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describe how aminolevulinic acid is made
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succinyl CoA with glycine lose CoA lose CO2 5 ALA Synthase deficiency of ALAS2 causes X-linked sideroblastic anemia |
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describe how porphobilinogen is made |
8 aminolevulinic acids make 4 ALA dehydratase condenses them deficiency of ALAD causes ALA dehydratase deficiency porphyria |
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describe how preuroporphyrinogen is made |
4 porphobilinogen make open ring uroporphyinogen synthase **deficiency causes acute intermittent porphyria AIP |
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describe how uroporphyrinogen III is made |
preuroporphyrinogen is fused uroporphyrinogen III cosynthase inversion of Ac and Pr in one ring deficiency causes Congenital Erythropoietic Porphyria CEP |
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describe how coproporphyrinogen III is made |
uroporphyrinogen decarboxylase removes 4 carboxylates and replaces with methyl groups **deficiency causes porphyria cutanea tarda PCT |
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describe how protoporphyrinogen is made |
coproporphyrinogen oxidase decarboxylates and oxidizes two propionyl groups to form vinyls deficiency causes hereditary coproporphyria HCP |
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describe how protoporphyrin is made |
protoporphyrinogen oxidase oxidizes deficiency causes variegate porphyria VP |
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describe how Heme is made |
ferrochelatase inserts Fe (II) into protoporphyrin **deficiency causes erythropoietic protoporphyria EPP |
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where does porphyrin biosynthesis occur |
bone marrow: hemoglobin for RBCs (continuous, 80%) liver: cytochrome p450 for detox (sporadic, 15%) control: not understood synthesis at ALAS genes liver- drugs, xenobiotics stimulate heme synthesis, exacerbate porphyrias (heme modulates ALAS1) bone marrow- Fe levels modulate translation of ALAS2 mRNA |
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describe heme breakdown |
released from dying RBCs in spleen heme oxygenase removes Fe, opens ring forming biliverdin biliverdin reductase converts to bilirubin antioxidant, causes jaundice liver/kidney help excrete/breakdown |
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describe porphyrias generally |
heritable flaws in porphyrin synthesis lesion causes buildup of toxic intermediates veriable penetrance diverse signs and symptoms skin photosensitivity (blistering, pain) abdominal pain, diverse neuropathy exacerbated by drugs, alcohol red urine porphyrins in urine/feces treatable: heme, phlebotomy, beta carotene |
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describe X linked sideroblastic anemia |
defect in ALAS2 gene x linked recessive, rare excess Fe accumulation, anemia (reduced heme) hepatomegaly, abdominal pain, cardiac myopathy microcytic anemia, increased Fe, pyridoxine stabalizes, phlebotomy |
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describe ALAD deficiency Porphyria (ADP) |
deficiency in ALAD gene
autosomal recessive, very rare pathology from excess ALA (neurotoxic) abdominal pain, diverse neuropathy AIP symptoms, increased ALA, no PBG in urine mimicked by Pb poisoning not much treatment |
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***describe acute intermittent porphyria (AIP) |
1/2 PBGD activity, buildup/excretion of porphyrins autosomal dominant, common acute episodes of abdominal pain, tachycardia, neuropathy (with alcohol/drugs) increased PBG/ALA in urine, normal fecal porphyrins treat with IV heme arginate and glucose |
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describe congenital erythropoietic porphyria (CEP) |
defect in UROS accumulates uroporphyrin/coproporphyrin autosomal recessive, rare photosensitivity from infancy (friable, blistered skin, infection and scarring, ehmolysis, splenomegaly) photosensitivity, pink urine, increased porphyrins in RBCs and urine protect skin, transfusions, marrow transplant |
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***describe porphyria cutanea tarda (PCT) |
decreased UROD activity, most common autosomal dominant, poorly penetrant chronic blistering, red urine, neural involvement exacerbated by ethanol diagnosis by fecal/urinary porphyrins HEP is homozygous form, very rare phlebotomy/chloroquine treatment |
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describe hereditary coproporhyria (HCP) and variegated porphyria (VP) |
rare, autosomal dominate lesiosn: HCP- CPO, VP- PPO HCP: milder than AIP, increased urinary, fecal coproporphyrin VP: common in south africa, finland, increased plasma porphyrins, RBC PBGD normal similar treatment to AIP, avoid stimulants, administer heme/glucose |
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***describe erythropoietic porphyria (EPP) |
deficiency of ferrochelatase autosomal recessive, common photosensitive skin, less scarring/deformity than CEP increased free protoporphyrin in RBC treat w/ beta carotene (liver disease is main risk) rarely caused by ALAS2 mutation, usually 3rd allele involved |
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describe lead poisoning |
pb inhibits ALAD mimics ADP, AIP abdominal pain, nausea, cognitive deficits, encephalopathy, seizures >10micrograms/L Pb increased RBC Zn protoporphyrin levels ingestion, acid releases Pb remove Pb source, chelation: CaEDTA, dimercaprol, succimer |
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describe photodynamic therapy in oncology |
PDT exploits photosensitizers that localize in tumors, illumination kills cancer cells selectively include ALA, heme derivatives and topically applied |
