CYP2R1
Encyclopedia
Vitamin D 25-hydroxylase also known as cytochrome P450 2R1 is an enzyme
that in humans is encoded by the CYP2R1 gene
.
vitamin D hydroxylase that converts vitamin D
into 25-hydroxyvitamin D (calcidiol), which is the major circulatory form of the vitamin.
in the CYP2R1 gene which results in the substitution of a proline
for a leucine
residue at codon 99 eliminates the enzyme activity and is associated with low circulating levels of 25-hydroxyvitamin D and classic symptoms of vitamin D deficiency. The gene product which it encodes, vitamin D 25-hydroxylase, has therefore been proposed as the key enzyme in the conversion of cholecalciferol
(vitamin D3) to calcidiol
. Calcidiol is subsequently converted by the action of 25-hydroxyvitamin D3 1-alpha-hydroxylase
to calcitriol
, the active form of vitamin D3 that binds to the vitamin D receptor
(VDR) which mediates most of the physiological actions of the vitamin.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the CYP2R1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
Vitamin D 25-hydroxylase is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This enzyme is a microsomalMicrosome
In cell biology, microsomes are vesicle-like artifacts re-formed from pieces of the endoplasmic reticulum when eukaryotic cells are broken-up in the laboratory; by definition, microsomes are not ordinarily present in living cells....
vitamin D hydroxylase that converts vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
into 25-hydroxyvitamin D (calcidiol), which is the major circulatory form of the vitamin.
Clinical significance
An inherited mutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
in the CYP2R1 gene which results in the substitution of a proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
for a leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
residue at codon 99 eliminates the enzyme activity and is associated with low circulating levels of 25-hydroxyvitamin D and classic symptoms of vitamin D deficiency. The gene product which it encodes, vitamin D 25-hydroxylase, has therefore been proposed as the key enzyme in the conversion of cholecalciferol
Cholecalciferol
Cholecalciferol is a form of vitamin D, also called vitamin D3 or calciol.It is structurally similar to steroids such as testosterone, cholesterol, and cortisol .-Forms:Vitamin D3 has several forms:...
(vitamin D3) to calcidiol
Calcidiol
Calcifediol , also known as calcidiol, 25-hydroxycholecalciferol, or 25-hydroxyvitamin D , is a prehormone that is produced in the liver by hydroxylation of vitamin D3 by the enzyme cholecalciferol 25-hydroxylase...
. Calcidiol is subsequently converted by the action of 25-hydroxyvitamin D3 1-alpha-hydroxylase
25-Hydroxyvitamin D3 1-alpha-hydroxylase
25-Hydroxyvitamin D3 1-alpha-hydroxylase also known as cytochrome p450 27B1 is a cytochrome P450 enzyme that in humans is encoded by the CYP27B1 gene....
to calcitriol
Calcitriol
Calcitriol , also called 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3, is the hormonally active form of vitamin D with three hydroxyl groups...
, the active form of vitamin D3 that binds to the vitamin D receptor
Calcitriol receptor
The calcitriol receptor, also known as the vitamin D receptor and also known as NR1I1 , is a member of the nuclear receptor family of transcription factors...
(VDR) which mediates most of the physiological actions of the vitamin.