Regucalcin/SMP30 is the lactone-hydrolyzing enzyme gluconolactonase (GNL) in the liver responsible for L-ascorbic acid (vitamin C) biosynthesis PMID:16585534. The lactonase reaction with l-gulono-γ-lactone is the penultimate step in vitamin C biosynthesis PMID:16585534. SMP30 knockout mice developed scurvy when fed vitamin C-deficient diet, confirming its essential role in vitamin C synthesis PMID:16585534.
Regucalcin was originally discovered as a calcium-binding protein in 1978 PMID:699201, though it lacks the typical EF-hand Ca2+-binding motif. It increases Ca2+-ATPase activity in heart mitochondria PMID:16786169. This regulation of Ca2+-ATPase activity is important for maintaining calcium homeostasis PMID:16786169.
Regucalcin expression is coordinately upregulated with tissue maturation and gradually downregulated with aging PMID:8794449. In liver, peak expression occurs in 5-day-old neonates with a second increase from day 7-10, then decreases in adults to about 1/3 of neonatal levels [PMID:8794449 from UniProt]. In kidney, expression increases from day 21, peaks at day 35, and remains high until 3 months.
Regucalcin is found in:
- Cytoplasm (confirmed by multiple sources)
- Nucleus (ISS evidence)
- Mitochondria (especially in heart, where it regulates Ca2+-ATPase) PMID:16786169
The protein is also known as Senescence Marker Protein 30 (SMP30) because its expression decreases with aging. Given its role in vitamin C synthesis and multiple regulatory functions, reduced expression with age may contribute to age-related dysfunction in calcium homeostasis, oxidative stress management, and metabolic regulation.