Role of 25-hydroxyvitamin D3 dose in determining rat 1,25-dihydroxyvitamin D3 production

Journal Article · Tue May 01 00:00:00 EDT 1990 · American Journal of Physiology; (USA)

OSTI ID:6871534

Vieth, R; McCarten, K; Norwich, K H ^[1]

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1. Univ. of Toronto, Ontario (Canada)

To understand the relationships among (1) the dose of 25-hydroxyvitamin D (25(OH)D) in vivo, (2) the activity of 1-hydroxylase in renal mitochondria, and (3) the production of 1,25-dihydroxyvitamin D (1,25(OH)2D) in vivo, we gave rats different chronic or acute doses of 25-hydroxyvitamin D3 (25(OH)D3). We followed the metabolism of intracardially administered (25-hydroxy-26,27-methyl-3H)cholecalciferol (25(OH)(3H)D3) for 24 h before killing by measuring extracts of serum by chromatography. Specific activity of 1-hydroxylase in kidney was measured at death. In rats given 0-2,000 pmol 25(OH)D3 chronically by mouth, there was a dose-dependent decline in the percent of serum radioactivity made up of 1,25-dihydroxy-(26,27-methyl-3H)cholecalciferol (1,25(OH)2(3H)D3) as well as a decline in mitochondrial 1-hydroxylase, and these correlated significantly (r = 0.83, P less than 0.001). Serum %1,25(OH)2(3H)D3 in this experiment ranged from 0.8 to 42%. A small part of this range could be accounted for by a faster metabolic clearance rate (MCR) of 1,25(OH)2D3 from rats supplemented with 25(OH)D3 (MCR, 2.12 +/- 0.10 ml/min) compared with rats restricted in vitamin D (MCR, 0.94 +/- 0.06 ml/min, P less than 0.001). The activity of 1-hydroxylase was by far the major factor determining serum %1,25(OH)2(3H)D3. When different acute doses of 25(OH)D3 were given to rats with identical specific activities of 1-hydroxylase, the resulting 1,25(OH)2D3 concentrations in serum correlated with the 25(OH)D3 dose (r = 0.99, P less than 0.001). We conclude that the behavior of 1-hydroxylase in vivo is analogous to the classic behavior in vitro of an enzyme functioning below its Michaelis constant (Km). The amount of 1-hydroxylase present in renal mitochondria determines the fraction (not simply the quantity) of 25(OH)D metabolized to 1,25(OH)2D3 in vivo.

• OSTI ID: 6871534
• Journal Information: American Journal of Physiology; (USA), Vol. 258; ISSN 0002-9513
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHOLECALCIFEROL
METABOLISM
HYDROXYLASES
ENZYME ACTIVITY
VITAMIN D
BIOSYNTHESIS
CLEARANCE
ISOTOPE DILUTION
KIDNEYS
MITOCHONDRIA
RATS
TRITIUM COMPOUNDS
ANIMALS
BODY
CELL CONSTITUENTS
ENZYMES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
MAMMALS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
RODENTS
SYNTHESIS
TRACER TECHNIQUES
VERTEBRATES
VITAMINS
550201* - Biochemistry- Tracer Techniques