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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

porphyra

= 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