Term
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Definition
| are a group of organic ring molecules that serve as cofactors for a number of proteins and enzymes |
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Term
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Definition
3 pyrroles fused together with Nitrogens being able to bind metal ions in the center
strong absorbance from conjugated ring structure |
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Term
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Definition
oxygen transport
transfer electrons between molecules
Redox Reactions
Nitric Oxide Synthase |
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Term
| Electron Transport Porphyrins |
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Definition
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Term
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Definition
cytochrome p450 - detox
catalase - peroxide distruction
cytochrome b5 stearoyl CoA desaturase |
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Term
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Definition
| porphyrins that generate toxic singlet oxygen or other reactive cmpounds when skin exposed to light |
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Term
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Definition
| in fluorescence spectra of heme proteins it is the strongest band with an extinction coefficient up to 150,000 per molar per cm. |
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Term
| Nonfluorescent porphyrins |
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Definition
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Term
| Step 1 in porphyrin biosynthesis |
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Definition
5-ALA Synthase (ALAS) condenses glycine and succinyl CoA to make delta-aminolevulinic acid
occurs in mitochondrion, requires pyridoxine |
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Term
| Step 2 in Porphyrin Biosynthesis |
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Definition
| 8 delta-aminolevulinates are condensed to form 4 porphobilinogens (PBG) through the enzyme porphobilinogen synthase |
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Term
| Step 3 in Porphyrin Biosynthesis |
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Definition
| 4 Porphobilinogens condense to form preuroporphyrinogen by uroporphyrinogen synthase in the cytosol |
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Term
| Step 4 in porphyrin biosynthesis |
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Definition
preuroporphyrinogen ring closes to form uroporphyrinogen III by the enzyme uroporphyrinogen III cosynthase
there is an inversion of Ac and Pr in "d" ring of product that only occurs enzymatically |
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Term
| Step 5 in Porphyrin Biosynthesis |
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Definition
| uroporphyrinogen III has 4 carboxylates removed to form Coproporphyrinogen III by enzyme uroporphyrinogen decarboxylase less water soluble Ac's now methyl groups |
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Term
| Step 6 in Porphyrin Biosynthesis |
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Definition
The enzyme coproporphyrinogen oxidase decarboxylates and oxidizes 2 propionyl groups from coproporphyrinogen III
this changes them to vinyl groups in protoporphyrinogen |
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Term
| Step 7 in Porphyrin Biosynthesis |
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Definition
protoporphyrinogen oxidase will oxidize protoprophyrinogen to protoporphyrin
the arrangement of the double bonds changes |
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Term
| Step 8 in Porphyrin Biosynthesis |
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Definition
| The enzyme ferrochelatase inserts Fe(II) into protoporphyrin IX to form heme |
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Term
| Sites of Porphyrin Biosynthesis |
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Definition
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Term
| Porphyrin Biosynthesis Control |
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Definition
poorly understood
in liver drugs, xenobiotics will stimulate synthesis
in bone marrow controlled by Fe levels |
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Term
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Definition
Heme is released from dying RBCs in spleen
Heme oxygenase removes Fe and opens ring to form biliverdin (green)
biliverdin is reduced by biliverdin reductase to bilirubin (yellow) |
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Term
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Definition
bilirubin travels back to liver on HSA to be bis-glucuronidated
bis-glucuronide is excreted with bile into intestine
urobilinogen converted microbially to stercobilin in gut |
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Term
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Definition
heritable flaws in porphyrin synthesis
leasion causes buildup of toxic intermediates
variable penetrance |
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Term
| Acute Intermittent Porphyria |
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Definition
caused by deficiency in uroporphyrinogen synthase
symptoms: abdominal pain, tachycardia, neuropathy induced by alcohol or drugs
from 1/2 normal PBG Deaminase leads to buildup of PBG, ALA
Autosomal Dominant inheritance, low penetrance
Diagnosed by : inc. urinary PBG, ALA; normal fecal porphyrins
Treatment: IV Heme arginate and glucose |
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Term
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Definition
deficiency in ferrochelatase
symptoms:photosensitive skin, liver disease can be severe
autosomal dominant
diagnosis free protoporphrin IX in feces, RBC's fluoresces
Treatment: beta-carotene to quench free radicals |
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Term
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Definition
deficiency in uroporphyrinogen decarboxylase
decreased UROD activity
2/3 acquired cases less familial AD; induced by liver disease, alcholism
chronic blistering lesions, red urine w/o neural involvement
diagnosis by urinary and fecal porphyrins
exacerbated by alcohol
treatment: phlebotomy, chloroquine (antimalaria drug) |
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Term
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Definition
symptoms: abdominal pain, nausea, cognitive deficits, encephalopathy, seizures
Pb inhibits ALAD by replacing catalytic Zn ions
>10ug/dL of Pb in blood
treatment; remove Pb source, then chelation |
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Term
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Definition
exploits photoinduced toxicity of porphyrins
precursors for treatment of cancers
good for skin, esophageal, lung, oral and bladder cancers |
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