Hibernation impact on the catalytic activities of the mitochondrial D-3-hydroxybutyrate dehydrogenase in liver and brain tissues of jerboa (Jaculus orientalis)

BACKGROUND: Jerboa (Jaculus orientalis) is a deep hibernating rodent native to subdesert highlands. During hibernation, a high level of ketone bodies i.e. acetoacetate (AcAc) and D-3-hydroxybutyrate (BOH) are produced in liver, which are used in brain as energetic fuel. These compounds are bioconverted by mitochondrial D-3-hydroxybutyrate dehydrogenase (BDH) E.C. 1.1.1.30. Here we report, the function and the expression of BDH in terms of catalytic activities, kinetic parameters, levels of protein and mRNA in both tissues i.e brain and liver, in relation to the hibernating process. RESULTS: We found that: 1/ In euthemic jerboa the specific activity in liver is 2.4- and 6.4- fold higher than in brain, respectively for AcAc reduction and for BOH oxidation. The same differences were found in the hibernation state. 2/ In euthermic jerboa, the Michaelis constants, K(M )BOH and K(M )NAD(+ )are different in liver and in brain while K(M )AcAc, K(M )NADH and the dissociation constants, K(D )NAD(+)and K(D )NADH are similar. 3/ During prehibernating state, as compared to euthermic state, the liver BDH activity is reduced by half, while kinetic constants are strongly increased except K(D )NAD(+). 4/ During hibernating state, BDH activity is significantly enhanced, moreover, kinetic constants (K(M )and K(D)) are strongly modified as compared to the euthermic state; i.e. K(D )NAD(+ )in liver and K(M )AcAc in brain decrease 5 and 3 times respectively, while K(D )NADH in brain strongly increases up to 5.6 fold. 5/ Both protein content and mRNA level of BDH remain unchanged during the cold adaptation process. CONCLUSIONS: These results cumulatively explained and are consistent with the existence of two BDH enzymatic forms in the liver and the brain. The apoenzyme would be subjected to differential conformational folding depending on the hibernation state. This regulation could be a result of either post-translational modifications and/or a modification of the mitochondrial membrane state, taking into account that BDH activity is phospholipid-dependent.