Overview
The enzyme Angiotensin-Converting Enzyme 2 (ACE2), recognized for its role in blood pressure regulation, has been identified with a distinct secondary function: the synthesis of sulfur-containing rings integral to certain cellular antioxidants. This newly observed activity involves ACE2 acting upon hydrogen sulfide (H2S) to generate persulfides and polysulfides, which are components of the cellular antioxidant defense mechanism.
Research Context
Antioxidants, such as vitamins C and E, function by neutralizing free radicals, specifically reactive oxygen species, before these can inflict damage upon genetic material or cell membranes. Such oxidative damage is implicated in the development of neurodegenerative diseases. The protection offered by antioxidants contributes to the preservation of cellular integrity. Hydrogen sulfide (H2S), a gasotransmitter, plays multiple roles in physiological processes, including cardiovascular regulation, neuronal signaling, and anti-inflammatory responses. Its involvement in antioxidant pathways has been a subject of ongoing investigation.
Findings
The research revealed that Angiotensin-Converting Enzyme 2 (ACE2) directly facilitates the production of sulfur rings. This process involves ACE2 utilizing hydrogen sulfide (H2S) as a substrate. The enzyme's catalytic action converts H2S into per- and polysulfide compounds. These sulfur-containing structures are then incorporated into various cellular antioxidants.
Specifically, the study identified that the catalytic site of ACE2, distinct from its known interaction with angiotensinogen, is responsible for this sulfur chemistry. The generated per- and polysulfides are crucial for the function of endogenous cellular antioxidant systems. This mechanism represents a previously unrecognized pathway by which ACE2 contributes to the broader cellular defense against oxidative stress.
The investigators observed that ACE2's capacity to produce these sulfur rings is measurable and occurs under physiological conditions, suggesting its relevance in vivo. The interaction between ACE2 and H2S to yield these sulfur species establishes a direct biochemical link between this enzyme and the body's internal antioxidant production, supplementing the roles of dietary antioxidants.
Why This Matters
The identification of ACE2's role in synthesizing sulfur rings for cellular antioxidants introduces a new understanding of this enzyme's biological functions, extending beyond its known cardiovascular and SARS-CoV-2 entry receptor roles. This discovery reveals a direct enzymatic pathway for the generation of endogenous antioxidants, complementing the protective effects of dietary antioxidants like vitamins C and E. Understanding this mechanism could inform future research into how cellular antioxidant defenses are regulated and potentially modulated.