Cytochrome P450 1α-hydroxylase (CYP27B1) (CYP27B1)

Cytochrome P450 1α-hydroxylase, encoded by the CYP27B1 gene, is a mitochondrial enzyme that serves as the rate-limiting step in the activation of vitamin D [1.3.3]. It catalyzes the conversion of 25-hydroxyvitamin D3 into 1,25-dihydroxyvitamin D3, also known as calcitriol, which is the primary ligand for the vitamin D receptor [1.2.2, 1.4.2]. While predominantly expressed in the renal proximal tubules, the enzyme is also found in extra-renal sites such as macrophages, skin, and bone, where it facilitates paracrine and autocrine signaling [1.2.3, 1.2.5]. This activation is crucial for maintaining systemic calcium and phosphate homeostasis and supporting skeletal health [1.1.4, 1.3.3]. Genetic mutations in the CYP27B1 gene lead to vitamin D-dependent rickets type 1A, a rare disorder of bone mineralization [1.3.3, 1.4.4]. In contrast, the ectopic expression of the enzyme in conditions like sarcoidosis or certain cancers can lead to hypercalcemia due to unregulated calcitriol production [1.2.2, 1.3.3]. Pharmacological intervention involves the use of calcitriol or synthetic analogs to treat deficiency, while inhibitors like ketoconazole or glucocorticoids are used to manage overactivity [1.2.2, 1.3.4]. The enzyme's activity is tightly regulated by parathyroid hormone, fibroblast growth factor 23, and calcitriol itself through feedback loops [1.2.2, 1.2.3].

Other names

25-hydroxyvitamin D3 1-alpha-hydroxylase [1.3.3]Calcidiol 1-monooxygenase [1.3.3]P450C1 alpha [1.3.3]1-alpha-OHase [1.3.3]Cytochrome P450 subfamily XXVIIB polypeptide 1 [1.3.3]

Inhibition of enzymatic activity, replacement of the endogenous enzymatic product (calcitriol), and transcriptional suppression of enzyme expression [1.2.2, 1.3.4].