CPOX is the gene location for Hereditary Coproporphyria and CPOX4 is located on that gene. Until now I had no idea there was a variation of HCP, just thought you either had gentic or acquired Porphyria and never had a clue there would be a twist like a mutation for Mercury. So if "genetic" Porphyria and Mercury caused Porphyria are on the same gene isn't it logical that BOTH are gentic? I dunno, I'm not a rocket scientist but if this isn't true I'm totally confused. Pentacarboxylporphyrin is a marker for Mercury. Again I bring up my mother. My mom had lots of Penta, Copro and Proto. My mother had Mercury poisoning. A mutation on CPOX4 causes one to possibly be more suseptable to Mercury exposure and a elevation in porphyrin. And Mercury causes a whole lot of stuff like immune problems, multiple symptoms and Porphyria. If there's a mutation called a polymorphism how is it acquired? And isn't Mercury implicated in MCS?
A cascade analysis of the interaction of mercury and coproporphyrinogen oxidase (CPOX) polymorphism on the heme biosynthetic pathway and porphyrin production.
Heyer NJ, Bittner AC Jr, Echeverria D, Woods JS.
Battelle Centers for Public Health Research and Evaluation, 1100 Dexter Avenue N, Suite 400, Seattle, WA 98109, USA.
Mercury (Hg) exposure in various forms remains a persistent public health concern in many parts of the world. In previous studies, we have described a biomarker of mercury exposure characterized by increased urinary concentrations of specific porphyrins, pentacarboxyporphyrin (5-CP) and coproporphyrin (4-CP), and the atypical keto-isocoproporphyrin (KICP), based on selective interference with the fifth (uroporphyrinogen decarboxylase, UROD) and sixth (coproporphyrinogen oxidase, CPOX) enzymes of the heme biosynthetic pathway. Whereas this response occurs in a predictable manner among approximately 85% of subjects with Hg exposure, an atypical porphyrinogenic response (APR) has been observed in approximately 15% of Hg-exposed persons, in which the three porphyrins that are affected by Hg, i.e., 5-CP, 4-CP and, KICP, are excreted in substantial excess of that predicted on the basis of Hg exposure alone. This APR has been attributed to a specific polymorphism in exon 4 of the CPOX gene (CPOX4). In the present study, we sought to further confirm the hypothesis that the observed changes in porphyrin excretion patterns might serve as a biomarker of Hg exposure and potential toxicity by statistically modeling the cascading effects on porphyrin concentrations within the heme biosynthetic pathway of Hg exposure and CPOX4 polymorphism in a human population with long-term occupational exposure to elemental mercury. Our results are highly consistent with this hypothesis. After controlling for precursor porphyrin concentrations, we demonstrated that 5-CP and 4-CP are independently associated with Hg concentration, while KICP is associated only with the CPOX4. An unpredicted association of Hg with heptacarboxyporphyrin (7-CP) may indicate a previously unidentified point of mercury inhibition of UROD. These findings lend further support to the proposed utility of urinary porphyrin changes as a biomarker of exposure and potential toxicity in subjects with mercury exposure. Additionally, these findings demonstrate the successful application of a computational model for characterizing complex metabolic responses and interactions associated with both toxicant exposure and genetic variation in human subjects.
PMID: 16214298 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/16214298?ordinalpos=15&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
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The CPOX gene provides instructions for the production of an enzyme called coproporphyrinogen oxidase. This enzyme is responsible for the sixth step in the production of heme, the iron-containing part of hemoglobin. Hemoglobin is the oxygen-carrying protein in red blood cells. Each step in heme production is controlled by a different enzyme, each of which is produced from a single gene. Coproporphyrinogen oxidase removes carbon and oxygen from coproporphyrinogen III (the product of the fifth step in the production of heme) to form protoporphyrinogen IX. This reaction occurs in structures known as mitochondria, the energy-producing centers within cells. Two additional enzymes modify protoporphyrinogen IX before it becomes heme. The heme molecule is incorporated into hemoglobin and packaged into red blood cells, or it is used in the liver for the production of certain liver enzymes
More than 35 mutations that cause hereditary coproporphyria (a type of porphyria) and a more severe form of the disorder, harderoporphyria, have been identified in the CPOX gene. One mutation in particular has been found in all families with harderoporphyria.
Then there's the way the acquired turns into heritable ... studies, for example, that trauma to the mother mouse are passed down, become encoded in the gene.
So there is no end and no beginning--or maybe I mean, no dualism. Sigh. And science tries *so* hard.
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