Enzymatic activation in vitamin D signaling - Past, present and future

Area of Science:

• Biochemistry
• Molecular Biology
• Endocrinology

Background:

• Vitamin D signaling regulates calcium homeostasis, bone health, and diverse cellular functions.
• Disruptions in vitamin D signaling are implicated in numerous diseases.
• Cytochrome P450 (CYP) enzymes are essential for vitamin D3 bioactivation into active metabolites.

Purpose of the Study:

• To review advancements in identifying vitamin D3 bioactivating enzymes and their genes.
• To evaluate species- and tissue-specific expression, catalytic functions, and genetic mutations of these enzymes.
• To critically discuss current knowledge gaps and the physiological importance of vitamin D hydroxylases.

Main Methods:

• Literature review focusing on identification and characterization of vitamin D bioactivating enzymes.
• Analysis of data on enzyme expression, substrate specificity, kinetics, and gene mutations.
• Discussion of vitamin D receptors and alternative bioactivation pathways.

Main Results:

• Significant progress has been made in identifying key vitamin D3 bioactivating enzymes.
• Data on enzyme characteristics, including species/tissue specificity and catalytic activity, have been compiled and evaluated.
• The roles of various vitamin D hydroxylases and alternative activation pathways are discussed.

Conclusions:

• Knowledge of vitamin D3 bioactivating enzymes has considerably advanced.
• Further research is needed to fully elucidate the mechanisms of vitamin D signaling and its diverse activities.
• Understanding these enzymatic pathways is critical for addressing vitamin D-related health conditions.