The enzyme: Renalase.

Area of Science:

• Biochemistry
• Enzymology
• Molecular Biology

Background:

• Renalase, discovered 10 years ago, has recently identified catalytic substrates.
• Its known physiological roles are primarily linked to its function as a secreted protein in blood.
• Recent findings suggest a potential intracellular enzymatic activity.

Purpose of the Study:

• To describe renalase as an enzyme.
• To present evidence for its intracellular catalytic function.
• To argue that this enzymatic function is distinct from its whole-organism physiological effects.

Main Methods:

• Identification and structural assignment of renalase substrates (2- and 6-dihydronicotinamide isomers of β-NAD(P)H).
• Comprehensive kinetic analyses and substrate specificity profiling across species.
• X-ray crystallography to determine the structure of renalase in complex with ligands.

Main Results:

• Renalase rapidly oxidizes 2- and 6-dihydronicotinamide isomers to β-NAD(P)+, transferring electrons to its FAD cofactor and forming hydrogen peroxide.
• Structural and kinetic data support an intracellular detoxification/metabolite repair function.
• The identified enzymatic activity is inconsistent with renalase acting solely as a secreted protein influencing systemic physiology.

Conclusions:

• Renalase possesses a distinct intracellular enzymatic function.
• This function likely involves the detoxification of dihydronicotinamide metabolites and repair of primary metabolism.
• The enzymatic activity of renalase should be considered separate from its broader physiological roles in circulation.