Porphyrins

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Porphyrins Bile Pigments
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Figure 322. Uroporphyrin III. A (acetate)
-CH2COOH P (propionate) -CH2CH2COOH.
Figure 321. The porphin molecule. Rings are
labeled I, II, III, and IV. Substituent positions
on the rings are labeled 1, 2, 3, 4, 5, 6, 7, and
8. The methenyl bridges (-HC) are labeled a, ß,
?, and d.
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Figure 329. Intermediates, enzymes, and
regulation of heme synthesis. The enzyme numbers
are those referred to in column 1 of Table 322.
Enzymes 1, 6, 7, and 8 are located in
mitochondria, the others in the cytosol.
Mutations in the gene encoding enzyme 1 causes
X-linked sideroblastic anemia. Mutations in the
genes encoding enzymes 28 cause the porphyrias,
though only a few cases due to deficiency of
enzyme 2 have been reported. Regulation of
hepatic heme synthesis occurs at ALA synthase
(ALAS1) by a repression-derepression
mechanism mediated by heme and its hypothetical
aporepressor. The dotted lines indicate the
negative (- ) regulation by repression. Enzyme 3
is also called porphobilinogen deaminase or
hydroxymethylbilane synthase.
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Diseases Associated with Hyperbilirubinemia

• Direct and indirect bilirubin values are used in
  the differential diagnosis of hyperbilirubinemia.
• Hyperbilirubinemia could be caused by increased
  bilirubin production decreased uptake into the
  liver cells, impaired conjugation, and
  interference with the secretion of conjugated
  bilirubin.

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Hemolytic jaundice

• results in increased production of bilirubin.
  Here more bilirubin is conjugated and excreted
  than normally, bu the conjugation mechanism is
  overwhelmed, and an abnormally
  large amount of unconjugated bilirubin is found
  in the blood.

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Gilbert's disease
It may be caused by an inability of the
hepatocytes to take up bilirubin from the blood.
As a result, unconjugated bilirubin accumulates.
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Physiological jaundice Crigler-Najjar syndrome

• They are conditions in which conjugation is
  impaired. Unconjugated
  bilirubin is retained by the body.

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Dubin-Johnson syndrome

• It is associated with inability of the
  hepatocytes to secrete conjugated bilirubin after
  it has been formed. Conjugated bilirubin returns
  to the blood.

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Biliary obstruction

• It is caused by biliary calculi causes backup and
  reabsorption of conjugated bilirubin.
• Blood levels of conjugated bilirubin increase.