Research article

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

Mostafa Kabine^1,2 , M'hammed Saïd El Kebbaj² , Assia Hafiani^1,2 , Norbert Latruffe¹ and Mustapha Cherkaoui-Malki¹

¹LBMC (GDR-CNRS n°2583), Université de Bourgogne, Faculté des Sciences Gabriel, 6, Boulevard Gabriel, 21000 Dijon, France

²Laboratoire de Biochimie, Faculté des Sciences-Aïn Chock, Université Hassan II, Casablanca, Morocco

author email corresponding author email

BMC Biochemistry 2003, 4:11doi:10.1186/1471-2091-4-11

Published:	10 September 2003

Abstract

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.