Physiological correlation between lactate dehydrogenase genotype and haemoglobin function in killifish.

TLDR: It is reported here that not only are ATP levels under genetic control, but they are also highly correlated with lactate dehydrogenase (LDH) phenotype, the first such correlation reported.

Abstract: ERYTHROCYTE organic phosphate concentration is known to be an heritable trait in both humans and rats1–3. In humans this trait has been correlated with genetic variability of both pyruvate kinase and hexokinase2. However, similar phenomena have not been reported in lower vertebrates. During our studies on the allosteric regulation of fish haemoglobins by ATP (ref. 4) we observed significant variability in red cell ATP concentrations among individuals of the killifish Fundulus heteroclitus, and wondered whether this variability in organic phosphate could be the result of a genetic component. Consequently, we analysed F. heteroclitus for red cell ATP, concomitantly screening for enzyme variants. We report here that not only are ATP levels under genetic control, but they are also highly correlated with lactate dehydrogenase (LDH) phenotype. To our knowledge, this is the first such correlation reported. Moreover, as ATP is the major allosteric modifier of F. heteroclitus haemoglobin–oxygen affinity5,6, this study provides a basis for an association between LDH and the fish's external environment through the physiological role of haemoglobin at the organism–environment interface.