Cytochrome P450 27B1

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Cytochrome P450 27B1
Properties of human protein
Mass / length primary structure <508 amino acids
Cofactor Heme thiolate
Identifier
Gene name CYP27B1
External IDs
Enzyme classification
EC, category 1.14.13.13 ,  oxygenase
Response type Addition of an oxygen atom
Substrate 25 (OH) vitamin D 3 , NADPH , H + , O 2
Products 1.25 (OH) 2 Vitamin D 3 , NADP + , H 2 O

Activation of 25 (OH) vitamin D 3 to 1.25 (OH) 2 vitamin D 3 by means of CYP27B1 or 1α-hydroxylase

The cytochrome P450, family 27, subfamily B, polypeptide 1 (short: CYP27B1 or conventionally: 1α-hydroxylase ) is a member of the cytochrome P450 enzyme superfamily. It hydroxylates the prohormone 25 (OH) vitamin D 3 to 1,25 (OH) 2 vitamin D 3 and activates it. The 1α-hydroxylase competes with the 24-hydroxylase for 25 (OH) D 3 , which inactivates the prohormone. Both enzymes are regulated in opposite directions.

genetics

The coding gene is located in the chromosome segment 12q12.1-q13.3. A defect in this gene leads to vitamin D-dependent rickets type 1 (see rickets ), which is treated with the enzyme product calcitriol 1,25 (OH) 2 D 3 (1,25-dihydroxycholecalciferol, also vitamin D 3 hormone) must become.

Occurrence

1α-hydroxylase is mainly found on the outside of the mitochondrial cell membrane of the kidney , but also in many other organs and tissues : prostate , breast , intestine , lungs , islet cells of the pancreas , monocytes , cells of the parathyroid gland , skin cells . Under normal circumstances, the kidneys in particular contribute to the calcitriol (1,25 (OH) 2 D 3 ) circulating in the blood (exceptions: pregnancy , chronic kidney failure , sarcoid , tuberculosis , rheumatoid arthritis ). The 1,25 (OH) 2 D 3 produced outside of the kidney, on the other hand, is primarily a locally limited (autocrine / paracrine) factor for cell-specific functions.

regulation

  • In the kidneys: The activity of 1α-hydroxylase in the kidneys is strictly regulated: it is activated by reduced calcium intake with food on the one hand directly via a reduction in serum calcium and on the other indirectly via an increase in parathyroid hormone . It is also activated by a reduced intake of phosphate with food, which happens indirectly through a mediating hormone (which hormone is not yet certain). It is inhibited by its product, 1,25 (OH) 2 D 3 itself, on the one hand directly and on the other hand by inhibiting parathyroid hormone activity.

Chronic renal insufficiency can lead to a P450 28B1 deficiency and, due to the resulting 1,25 (OH) 2 D 3 deficiency, to what is known as "renal rickets ".

  • In tissues outside the kidney: the regulation is different. Here the rate of 1.25 (OH) 2 D 3 production is primarily dependent on locally effective factors such as e.g. B. cytokines , growth factors . The mechanisms involved are not yet fully understood. Liu et al. showed in 2006 that activation of macrophages via the TLR (Toll Like Receptor) also leads to a production of 1,25 (OH) 2 D 3 . The mechanism is used for the production of the body's own bactericides ( cathelicidin ), which in turn is regulated with the help of the VDR receptor.

See also

Individual evidence

  1. ↑ a b Dusso AS, Brown AJ, Slatopolsky E: Vitamin D . In: Am. J. Physiol. Renal Physiol. . 289, No. 1, July 2005, pp. F8-28. doi : 10.1152 / ajprenal.00336.2004 . PMID 15951480 .
  2. ↑ Liu PT, Stenger S, Li H, et al : Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response . In: Science (journal) . 311, No. 5768, March 2006, pp. 1770-3. doi : 10.1126 / science.1123933 . PMID 16497887 .

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Vitamin D Metabolism  - Learning and Teaching Materials
Wikibooks: Biochemistry and Pathobiochemistry: Biotransformation  - Learning and Teaching Materials