11 Beta-hydroxysteroid dehydrogenases type 1 and 2 (11 beta-HSD1 and 11 beta-HSD2) are microsomal
enzymes responsible for the interconversion of
cortisol into the inactive form
cortisone and vice versa. 11 beta-HSD1 is mainly present in the liver, and has predominantly
reductase activity although its function has not yet been elucidated.
11 beta-HSD2, present in
mineralocorticoid target tissues such as the kidney, converts
cortisol into
cortisone. Reduced activity due to inhibition or mutations of
11 beta-HSD2 leads to
hypertension and
hypokalemia resulting in the
Apparent Mineralocorticoid Excess Syndrome (AMES). Like humans, cats are highly susceptible for
hypertension. As large species differences exist with respect to the kinetic parameters (K(m) and V(max)) and amino acid sequences of both
enzymes, we determined these characteristics in the cat. Both
enzyme types were found in the kidneys. 11 beta-HSD1 in the feline kidney showed bidirectional activity with predominantly
dehydrogenase activity (
dehydrogenase: K(m) 1959+/-797 nM, V(max) 766+/-88 pmol/mg*min;
reductase: K(m) 778+/-136 nM, V(max) 112+/-4 pmol/mg*min).
11 beta-HSD2 represents a unidirectional
dehydrogenase with a higher substrate affinity (K(m) 184+/-24 nM, V(max) 74+/-3 pmol/mg*min). In the liver, only 11 beta-HSD1 is detected exerting
reductase activity (K(m) 10462 nM, V(max) 840 pmol/mg*min). Sequence analysis of conserved parts of 11 beta-HSD1 and
11 beta-HSD2 revealed the highest homology of the feline
enzymes with the correspondent
enzymes found in man. This suggests that the cat may serve as a suitable model species for studies directed to the pathogenesis and treatment of human diseases like AMES and
hypertension.