Kinetic Mechanism of Nicotinamide N-Methyltransferase.
Level 5 - mechanism / opinion, no new human data
In vitro enzyme kinetics study without human or animal clinical data.
PubMed 30148963 · doi:10.1021/acs.biochem.8b00775
What was done
Initial velocity, product inhibition, and dead-end analogue inhibition kinetic experiments were conducted on purified human nicotinamide N-methyltransferase (NNMT) to characterize its catalytic and substrate-binding mechanism.
What was found
The abstract reports no numerical kinetic parameters (e.g., Km, kcat, or Ki values). Qualitatively, human NNMT follows a rapid equilibrium ordered kinetic mechanism: the enzyme binds S-adenosylmethionine (SAM) first, followed by nicotinamide (NAM); following methyl transfer, methylated NAM and S-adenosylhomocysteine are released consecutively.
Why it matters
Defining the precise binding and release sequence of NNMT provides a biochemical framework to guide the rational design of small-molecule inhibitors and activity-based chemical probes targeting NNMT-driven metabolic and epigenetic dysregulation.
Limits
This is strictly an in vitro biochemical study; cellular uptake, physiological substrate fluctuations, and in vivo efficacy of targeting this mechanism were not assessed. Specific numerical kinetic constants are not reported in the abstract.
Cited by
- supports High levels of NAD clearance through NNMT consume methyl groups and reduce SAMe.