The first step occurs in the liver, where vitamin D is hydroxylated to 25-hydroxyvitamin D (25-OHD) by hepatic 25-hydroxylase
. The second step occurs mainly in the kidney, where 25-OHD is further hydroxylated by the mitochondrial vitamin D 1[alpha]-hydroxylase to the biologically active hormone 1,25-dihydroxyvitamin D (1,25-[OH.sub.2]D), which binds to its nuclear receptor and exerts its biological activities (1,2,3).
Besides, the enzymes such as 1-hydroxylase and 25-hydroxylase
that are involved in formation of an active form of this vitamin are low in persons with high BMI.
1-[alpha]-hydroxylase (CYP27B1) and 25-hydroxylase
convert vitamin D to its active form, 1,25 dihydroxy-vitamin [D.sub.3] (1, 25[(OH).sub.2][D.sub.3]), which exerts its effect by combining with the nuclear vitamin [D.sub.3] receptor (VDR).
It is basically a hormone obtained after hydroxylation at carbon number 25 by enzyme 25-hydroxylase
in the liver to form 25-hydroxyvitamin D, followed by another hydroxylation at carbon number 1 by the enzyme 1a hydroxylase to form, 1,25-dihydroxyvitamin D, active form vitamin D.
The enzyme vitamin D 25-hydroxylase
metabolizes ergocalciferol and cholecalciferol in the liver and converts them to the 25(OH)D forms of 25(OH)D2 and 25(OH)[D.sub.3], respectively.
The formation of 25-OHC is catalyzed by the enzyme cholesterol 25-hydroxylase
(Ch25h) [29, 30].
The release of IFN-[gamma], a T helper- (Th-)1 cytokine that is central to regulating the obesity-induced adipose tissue inflammatory response [36, 37], upregulates the production of 25-hydroxycholesterol by increased 25-hydroxylase
10 demonstrated the inhibition by PIs of the 25-hydroxylase
and the 1a-hydroxylase involved in vitamin D metabolism.
Vitamin D 25-hydroxylase
Four decades of searching, are we there yet?
In addition, there is reason to believe that 25(OH)D is a marker both of gonadal function (vitamin D is 25-hydroxylated by gonadal tissues) and of the capacity of the liver to detoxify xenobiotics (hepatic 25-hydroxylase
enzymes are also involved in phase 1 detoxification pathways).
From here, vitamin D3 is transported to your liver, where it is combined with the 25-hydroxylase
enzyme to form calcidiol (25-hydroxycholecalciferol or 25-hydroxyvitamin D).