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Testosterone dehydrogenase activity in koala liver: characterisation of cofactor and steroid substrate differences

Stupans, I, Kong, S, Kirlich, A, McKinnon, RA & Murray, M 2000, Comparative Biochemistry and Physiology, part C, pp. 245-250.

The activity of testosterone dehydrogenase, or 17b-HSD, in the liver was evaluated in koalas, tammar wallabies, rats and humans. The activity was higher in koalas than wallabies, but was similar when NAD, an enzyme cofactor, was used in assays. Enzyme kinetics showed testosterone dehydrogenase mostly uses NADP as a cofactor in the liver of the koala, and that this pathway is utilised to a lesser extent in wallabies, human and rats than it is in koalas.

  Testosterone dehydrogenase is an enzyme that is involved in metabolism of sex hormones, utilising NAD and NADP as cofactors in oxidizing testosterone in koala liver. Its activity was measured here in small cellular pouches, or microsomes, of liver cells. The activity of 17b-HSD with NADP in microsomes was found to be highest in koalas (11.64 nmoles/mg protein/min). Although the enzyme’s NAD-mediated activity in microsomes was highest in rats, it was higher in koala and human microsomes than it was in cytosol, the cell’s fluid. Enzymatic tests showed Km, a biochemical constant, did not change when testosterone was added to the enzyme. Km of 17b-HSD was high with NAD cofactor, 13.9-18.5mM, and low with NADP cofactor, 0.28-0.43mM. Potential inhibitors of the reaction were investigated and 17b-estradiol was found to inhibit NADP-mediated 17b-HSD activity by 25-45% and presence of NAD did not affect the inhibition. Koalas’ 17b-HSD oxidative activity is similar to adults in pouch young.

  This study has shown that 17b-HSD activity in microsomes is different in koalas compared to other animals. In the reductive pathway, NADPH is preferred in koalas which is again different from other species. Some of the steroids tested and cofactors NAD and NADP do not appear to compete for the binding site of 17b-HSD enzyme. 17b-estradiol was the exception, which means it binds and reacts with 17b-HSD. It is unusual that 17b-HSD’s activity is similar between adults and young, as its activity is much higher in young rats than in adult rats. Compared to other mammals, koalas are unique in their diet which consists almost exclusively of eucalyptus leaves. Metabolic enzymes that are involved in this digestive process have not been studied and are likely to be different from other animals. NADP-mediated oxidation of steroids by 17b-HSD is yet another example of koala’s unique metabolism that is different from tammar wallabies, rats and humans.

  Further studies with larger sample sizes are needed to determine if there is a difference in 17b-HSD activity between male and female koalas. Gene expression of 17b-HSD in koalas should also be studied to explain differences in activity between species.

 

Summarised by Alexandra Selivanova

 

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