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Isozymes Provide a Means of Regulation Specific to Distinct Tissues and Developmental Stages

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Isozymes Provide a Means of Regulation Specific to Distinct Tissues and Developmental Stages
Figure 10.26. Chemical Basis of the Bohr Effect. In deoxyhemoglobin, shown here, three amino acid residues form
two salt bridges that stabilize the T quaternary structure. The formation of one of the salt bridges depends on the
presence of an added proton on histidine β146. The proximity of the negative charge on aspartate 94 favors protonation
of histidine β146 in deoxyhemoglobin.
I. The Molecular Design of Life
10. Regulatory Strategies: Enzymes and Hemoglobin
10.3. Isozymes Provide a Means of Regulation Specific to Distinct Tissues and
Developmental Stages
Isozymes or isoenzymes, are enzymes that differ in amino acid sequence yet catalyze the same reaction. Usually, these
enzymes display different kinetic parameters, such as K M, or different regulatory properties. They are encoded by
different genetic loci, which usually arise through gene duplication and divergence (Section 2.2.5). Isozymes differ from
allozymes, which are enzymes that arise from allelic variation at one gene locus. Isozymes can often be distinguished
from one another by biochemical properties such as electrophoretic mobility.
The existence of isozymes permits the fine-tuning of metabolism to meet the particular needs of a given tissue or
developmental stage. Consider the example of lactate dehydrogenase (LDH), an enzyme that functions in anaerobic
glucose metabolism and glucose synthesis. Human beings have two isozymic polypeptide chains for this enzyme: the H
isozyme highly expressed in heart and the M isozyme found in skeletal muscle. The amino acid sequences are 75%
identical. The functional enzyme is tetrameric, and many different combinations of the two subunits are possible. The H4
isozyme, found in the heart, has a higher affinity for substrates than does the M4 isozyme. The two isozymes also differ
in that high levels of pyruvate allosterically inhibit the H4 but not the M4 isozyme. The other combinations, such as
H3M, have intermediate properties depending on the ratio of the two kinds of chains. We will consider these isozymes in
their biological context in Chapter 16.
The M4 isozyme functions optimally in an anaerobic environment, whereas the H4 isozyme does so in an aerobic
environment. Indeed, the proportions of these isozymes are altered in the course of development of the rat heart as
the tissue switches from an anaerobic environment to an aerobic one (Figure 10.27A). Figure 10.27 B shows the tissuespecific forms of lactate dehydrogenase in adult rat tissues. The appearance of some isozymes in the blood is indicative
of tissue damage and can be used for clinical diagnosis. For instance, an increase in serum levels of H4 relative to H3M is
an indication that a myocardial infarction, or heart attack, has occurred.
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