Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

II. Porphyrins
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two vinyl groups are converted to hydroxy-ethyl groups,
the product is hematoporphyrin IX. If the two vinyl groups
are replaced by hydrogen atoms, the product is deuteroporphyrin
IX. Protoporphyrin and deuteroporphyrin normally
occur in feces but are primarily products of intestinal bacterial
degradation.
B . Synthesis of Porphyrins and Heme
The initial steps in the pathway for porphyrin and heme
biosynthesis begins with the incorporation of the methyl
carbon (C-2) and nitrogen atom of glycine into the porphyrin
ring and ultimately into the heme of hemoglobin.
Porphyrin metabolism and the porphyrias have been periodically
reviewed ( Elder and Sheppard, 1982 ; Hindmarsh,
1986 ; Sassa, 2006 ; Sassa and Kappas, 2000 ).
The methyl carbons (C-2) of glycine supply 8 of the 34
carbons of protoporphyrin: one for each of the four methene
bridges and one for each of the pyrrole rings ( Fig. 8-3 ).
The carboxyl carbon atom of glycine is given off as CO 2 and
is not incorporated into the protoporphyrin molecule ( Fig.
8-3 ). The direct incorporation of the nitrogen or the methyl
carbon glycine into the heme of hemoglobin has been the
basis for a useful technique to label the erythrocyte and to
measure its survival time. After administering 15 N-glycine,
the concentration of 15 N in heme rises rapidly, remains constant
for a time, and then falls. Mathematical analysis of the
curve indicates a survival time of 120 days for the human
erythrocyte. On a similar basis, methyl carbon labeled glycine
has been used to determine the life span of the erythrocytes
of a number of domestic animals ( Table 8-1 ).
The remaining carbons of protoporphyrin are supplied
by the tricarboxylic acid (TCA) cycle intermediate, succinyl-CoA.
An outline of the pathway of heme and porphyrin
synthesis is given in Figure 8-4 , which depicts the
compartmentalization of their pathways between the mitochondria
and cytosol. The nomenclature of the enzymes of
porphyrin synthesis varies among authors, so a guide to the
nomenclature of the enzymes is provided in Table 8-2 .
FIGURE 8-3 The synthetic pathway
for protoporphyrin and heme.
Note that two enzymes are required to
catalyze the formation of UROgenIII.
The circled numbers correspond to
the enzymes listed in Table 8-2.