enzymology-2018-keynote

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E u r o S c i C o n C o n g r e s s o n
Enzymology and
Molecular Biology
Insights in Enzyme Research
ISSN: 2573-4466
A u g u s t 1 3 - 1 4 , 2 0 1 8
P a r i s , F r a n c e
Enzymology 2018
Page 19
Rona R Ramsay, Insights Enzyme Res 2018, Volume 2
DOI: 10.21767/2573-4466-C1-001
Monoamine oxidase (MAO) has been a drug target for 60 years, particularly to
treat neuropsychiatric disorders. The flavin-containing monoamine oxidases
(MAO A and MAO B) located on the outer membrane of mitochondria oxidise
neurotransmitter amines and generates hydrogen peroxide. In the brain, inhibition
of MAO increases neurotransmitter levels, alleviating depression or helping
compensate for cell loss in neurodegeneration. In the periphery, MAO activity is
essential for protection against biogenic amines. MAO also metabolizes many
amine drugs, an important factor in pharmacokinetics. Kinetic studies of the two
forms of MAO (MAO A and MAO B) have revealed that ligands bind differently to
the oxidized and reduced forms, and have facilitated design of selective inhibitors.
This presentation will summarize the structure and function of MAO and its
inhibition by current drugs. Most successful drugs are irreversible inhibitors that
inactivate MAO by forming a flavin adduct, so that activity in vivo is recovered only
by new protein synthesis. Recent data that resolves the controversial structure
of adduct will be presented, along with steady-state and stopped-flow kinetics
of adduct formation. Going forward, computational methodologies, medicinal
chemistry, and enzymology facilitate structure-based drug design for new multi-
target compounds that inhibit not only MAO, but also other targets where binding
might prevent neurodegeneration in one multi-target compound.
Biography
Rona R Ramsay has pursued her Research in Enzymology in
Cambridge, California and St Andrews (where she has lectured
for 23 years), focusing on mitochondrial enzymes, investigating
howtheseenzymesworkandhowtheyareregulated,techniques
of kinetic analysis, spectroscopy, structural determination,
inhibitor studies, and molecular biology are combined with
molecular modelling to elucidate mechanism and guide drug
discovery. Her historic works include the discovery of the
carnitine carrier and the regulation of carnitine acyltranferases
in fatty acid metabolism; the metabolism of the neurotoxin
MPTP and identification of Complex I in the respiratory chain
as the target of MPP+ toxicity; and the kinetics of iron-sulfur
proteins and of flavoenzymes. Her Current research focusses
on monoamine oxidases involves collaborations with medicinal
chemists and neuropharmacologists to identify new multi-
target molecules against neurodegenerative diseases. ORCHID
ID:
Kinetics, inhibition and drug design for
monoamine oxidases
Rona R Ramsay
University of St Andrews, Scotland, UK