A.12 Enzyme structure and species
The structure of a specific enzyme may vary from species to species. These
differences, which tend to be the replacement of one or a few amino acid residue
by alternative residues, may be important in that they may form selective targets
for drugs. For example, differences in the structures of human and bacterial
DHFR result in the antibacterial trimethoprin binding specifically to bacter-
ial DHFR (see section 7.5.1).
The structure of an enzyme can also vary within a person, since different
genes may encode enzymes that catalyse the same reaction. These enzymes are
known asisozymes. Isozymes are often specific for different types of tissue. For
example, lactate dehydrogenase (LDH) is produced in two forms, the M-type
(muscle) and the H-type (heart). The M-type is predominates in tissue subject to
anaerobic conditions, such as skeletal muscle and liver tissue, whereas the
H-type predominates in tissue under aerobic conditions, such as the heart.
Isozymes may be used as a diagnostic aid. For example, the presence of
H-type LDH in the blood indicates a heart attack, since heart attacks cause
the death of heart muscle with the subsequent release of H-type LDH into the
circulatory system.
Variations in the structures of enzymes within a species can also occur
between and within ethnic groups of the same species. For example, a number
of different alcohol dehydrogenase isoenzymes have been observed in some
Asians.
260 APPENDIX 12 ENZYME STRUCTURE AND SPECIES