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Vitamin D-binding protein (DBP), also/originally known as gc-globulin (group-specific component), is a protein that in humans is encoded by the GC gene. [ 5 ] [ 6 ] DBP is genetically the oldest member of the albuminoid family and appeared early in the evolution of vertebrates.
Metabolites produced from vitamin D 2 tend to bind less well to the vitamin D-binding protein. [3] Vitamin D 3 can alternatively be hydroxylated to calcifediol by sterol 27-hydroxylase, an enzyme coded for by gene CYP27A1, but vitamin D 2 cannot. [3] Ergocalciferol can be directly hydroxylated at position 24 by the enzyme coded for by CYP27A1. [3]
The second hydroxylation occurs mainly in the kidney through the action of CYP27B1 to convert 25-OH vitamin D 3 into 1,25-dihydroxycholecalciferol (calcitriol, 1,25-(OH) 2 vitamin D 3). All these metabolites are bound in blood to the vitamin D-binding protein.
CYP2R1 is cytochrome P450 2R1, an enzyme which is the principal vitamin D 25-hydroxylase. [5] [6] In humans it is encoded by the CYP2R1 gene located on chromosome 11p15.2. [7]It is expressed in the endoplasmic reticulum in liver, where it performs the first step in the activation of vitamin D by catalyzing the formation of 25-hydroxyvitamin D. [8]
Calcifediol binds in the blood to vitamin D-binding protein (also known as gc-globulin) and is the main circulating vitamin D metabolite. [4] [5] Calcifediol has an elimination half-life of around 15 to 30 days. [4] [9] Calcifediol is further hydroxylated at the 1-alpha-position in the kidneys to form 1,25-(OH) 2 D 3, calcitriol.
A number of blood transport proteins are evolutionarily related in the albumin family, including serum albumin, alpha-fetoprotein, vitamin D-binding protein and afamin. [3] [4] [5] This family is only found in vertebrates. [6] Albumins in a less strict sense can mean other proteins that coagulate under certain conditions.
Transcription of the CYP24A1 gene is markedly inducible by 1,25-(OH) 2 D 3 binding to the vitamin D receptor. [6] The gene has a strong, positive vitamin D response element in the promoter . Through regulation of CYP24A1 expression, a negative feedback control system is created to limit the effects of 1,25-(OH) 2 D 3 .
Ergocalciferol and metabolites have lower affinity to the vitamin D-binding protein compared to the D 3 counterparts. The binding affinity of ercalcitriol to the vitamin D receptor is similar to that of calcitriol. [22] Ergocalciferol itself and metabolites can be deactivated by 24-hydroxylation. [23]
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