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

Chapter 8
Porphyrins and the Porphyrias
J. Jerry Kaneko
Department of Pathology, Microbiology, and Immunology
School of Veterinary Medicine
University of California, Davis
Davis, California
I. INTRODUCTION
II. PORPHYRINS
A. Structure of the Porphyrins
B. Synthesis of Porphyrins and Heme
III. METHODOLOGY
A. Urinary Porphyrins
B. Fecal Porphyrins
C. Blood Porphyrins
D. Porphobilinogen
IV. PORPHYRIAS
A. Classification
B. Erythropoietic Porphyrias
C. Hepatic Porphyrias
D. Porphyrinurias (Acquired Toxic Porphyrias)
REFERENCES
I . INTRODUCTION
The metal-porphyrin complexes are found widespread
in nature as constituents of compounds of fundamental
importance in the metabolic processes of life. The photosynthetic
pigment of plants, chlorophyll, is a magnesium
porphyrin. The iron-porphyrin complexes of animals are
found as prosthetic groups of proteins, including the hemoglobins,
myoglobins, and the heme enzymes peroxidase,
catalase, and the cytochromes. The porphyrins also exist
in nature in their free state or as zinc complexes, and it is
this group that is associated with the porphyrias and the
porphyrinurias.
Present knowledge of the porphyrins has its basis in the
classic studies of the German physician and chemist Hans
Fischer, whose work on the porphyrins dates back to 1915.
The development of elegant methods of detection and identification
of porphyrins and sophisticated enzymological
techniques have resulted in the present clear understanding
of the mechanisms of porphyrin biosynthesis and the biochemical
and molecular bases for the disorders of porphyrin
metabolism.
II . PORPHYRINS
A . Structure of the Porphyrins
The parent nucleus of the porphyrins is a cyclic tetrapyrrole,
which consists of four pyrrole nuclei with their
α (adjacent to the β ) carbon atoms linked together by methene
(-C ) bridges. This compound is called porphin and
is shown in Figure 8-1 . The various synthetic and naturally
occurring porphyrins are derivatives of porphin, distinguished
from each other by the type and position of the
radicals substituted for the hydrogen atoms at positions 1
through 8. For convenience in discussing the substitutions,
the simplified representation of the porphin nucleus as
shown in Figure 8-1 is used.
The classification of the porphyrins is based on the
synthetic porphyrin, etioporphyrin (ETIO), in which two
different radicals are substituted at positions 1 through 8.
The substituted radicals are four methyl (M) and four ethyl
(E) groups. The number of structural isomers possible with
these eight substituted radicals is four, as shown at the top
of Figure 8-2 . The naturally occurring porphyrins are only
those in which the positioning of their substituted radicals
correspond to isomer I or III of etioporphyrin, ETIO I and
ETIO III. This observation led Fischer to speak of a “ dualism
” of porphyrins in nature, which is in essential agreement
with present knowledge of the biosynthesis of the
Clinical Biochemistry of Domestic Animals, 6th Edition 241
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