chapter 29
Metabolism of Iron and Heme
FIG U RE 29-5
Synthesis o f uroporphyrinogen I and III. The latter is the biologically useful isomer, and its form ation requires the action
o f uroporphyrinogen-III synthase. Ac, -C H 2CO OH ; P, -C H 2C H 2COOH.
inner mitochondrial membrane, and its active site faces the
cytosolic side of the membrane. Formation of heme is ac-
complished by ferrochelatase (or heme synthase), which
incorporates Fe2+ into protoporphyrin and is inhibited by
lead. Zinc can function as a substrate in the absence of iron.
Disorders o f Heme Biosynthesis
The porphyrias are a group of disorders caused by
abnormalities in heme biosynthesis. They are inherited
and acquired disorders characterized by excessive accu-
mulation and excretion of porphyrins or their precursors.
Defects in any one of the eight enzymes involved in
heme biosynthesis may cause inherited porphyrin-related
disorders (Figure 29-9). Porphyrins have a deep red or
purple color (Greek
= purple). Porphyrins are
excreted by different routes, depending on their water
solubility. For example, uroporphyrin with its eight car-
boxylic group substituents is more water-soluble than
the porphyrins derived from it and is eliminated in the
urine, whereas protoporphyrin (which contains two car-
boxylic groups) is excreted exclusively in bile. Copropor-
phyrin has four carboxylic groups and is found in bile
and urine.
These disorders are associated with acute or cuta-
neous manifestations (or both). In the acute state, the
presentation may include abdominal pain, constipation,
hypertension, tachycardia, and neuropsychiatrie mani-
festations. Cutaneous problems consist of photosensi-
tivity (itching, burning, redness,
swelling, and scar-
ring), hyperpigmentation, and sometimes hypertrichosis
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