Background
Anaplerosis Associates (R), Inc., (formerly DMC Consulting, Inc.)
was formed by David M. Cohen, Ph.D., in January 2006. After
several decades of education, training and research in computer
science, mathematics and physiology, he wanted to offer his
ideas and skills in mathematical modeling in metabolism to the
larger industrial community.
Cohen's curriculum vitae can be found here.
Selected Publications of David M. Cohen, Ph.D.:
>> Modeling (rate constants): This is a mathematical treatment
of the observed rate constants in experiments using isotopically
labeled precursors. How does the single dominant rate constant
relate to the metabolic structure of the pathways ? What can be
inferred from the rate constant ? Can an explanation of the
dynamics in terms of the dominant rate constant be used to
estimate the rate of the metabolic pathway ? See the
publication in Metabolic Engineering: dominant rate constant
>> Modeling (syntactic rules): We participated in the
development of a novel approach to simulation of metabolic
pathways, the "syntactic" approach. This is particularly
well-suited to the investigation of the relationship between the
labeling patterns of molecules in a pathway (after providing
isotopically labeled substrate) and the rate of the pathway.
These positional isotopomers of the metabolic intermediates can
be measured using nuclear magnetic resonance (NMR)
spectrosopy. Mass isotopomers of the metabolites are the
labeled compounds in which the total number of isotopic labels
per molecule is assessed, rather than the position of each label.
For the relationship to NMR spectroscopy and application to
heart metabolism, see the following paper: syntactic modeling.
A detailed description of the computer simulation can be found in
the following paper: syntax - the program . For a PowerPoint
slideshow containing explanations of features of the syntactic
modeling approach, click here: Syntactic Model: Slides
The application of the syntactic approach for the testing of
algebraic formulas used to calculate metabolic rates can be
found in the following papers: heart CAC and anaplerosis.
>> Brain Metabolism: There are several aspects that we
investigated. First, on the basis of the analysis of atomic flow in
the citric acid cycle and the metabolic pathways in the brain, we
argued that the gradual reduction in the activity in a single
enzyme (with age or with disease) would suffice to limit the
production of energy in the cerebral neurons. Glutamine
synthetase, primarily a glial enzyme, was one of two enzymes
whose activities were found to be decreased in the postmortem
brains of patients with Alzheimer's disease compared to
nonaffected aged individuals. Inhibition of this enzyme would
necessarily impair neuronal energy production. See the specific
paper (inhibition of glutamine synthetase)-as well as the review
article concerning the relationship of aging, Alzheimer's disease
and metabolic changes (such as diabetes) (aging, metabolism
and Alzheimer's disease).
A second major area of our investigation concerned the use of
stable isotopes (non-radioactive isotopes) to measure rates of
metabolism in the brain. We developed a new method for
estimation of cerebral glucose metabolism (CMRgluc) using in
vivo nuclear magnetic resonance spectroscopy (measuring
cerebral metabolic rates with 13C NMR). We did additional
studies with a metabolic inhibitor which we showed to be
protective to brain metabolism during ischemic attacks
(protection by 2-deoxyglucose in cerebral ischemia).
A third major study concerned the source of nitrogen atom used
to synthesize compounds in the brain (glutamate, glutamine, etc).
This study investigated the importance of leucine as a nitrogen
carrier (leucine-nitrogen metabolism).
>> Heart metabolism: We performed experimental studies in the
isolated, working rat heart and found the lack of a complete
cycling in glutamate-glutamine (glutamine cycling and
corrigendum). In addition, we investigated current methods for
estimating the rate of the pentose phosphate pathway in heart
(pentose phosphate pathway and letter).
Anaplerosis Associates (R), Inc., (formerly DMC Consulting, Inc.)
was formed by David M. Cohen, Ph.D., in January 2006. After
several decades of education, training and research in computer
science, mathematics and physiology, he wanted to offer his
ideas and skills in mathematical modeling in metabolism to the
larger industrial community.
Cohen's curriculum vitae can be found here.
Selected Publications of David M. Cohen, Ph.D.:
>> Modeling (rate constants): This is a mathematical treatment
of the observed rate constants in experiments using isotopically
labeled precursors. How does the single dominant rate constant
relate to the metabolic structure of the pathways ? What can be
inferred from the rate constant ? Can an explanation of the
dynamics in terms of the dominant rate constant be used to
estimate the rate of the metabolic pathway ? See the
publication in Metabolic Engineering: dominant rate constant
>> Modeling (syntactic rules): We participated in the
development of a novel approach to simulation of metabolic
pathways, the "syntactic" approach. This is particularly
well-suited to the investigation of the relationship between the
labeling patterns of molecules in a pathway (after providing
isotopically labeled substrate) and the rate of the pathway.
These positional isotopomers of the metabolic intermediates can
be measured using nuclear magnetic resonance (NMR)
spectrosopy. Mass isotopomers of the metabolites are the
labeled compounds in which the total number of isotopic labels
per molecule is assessed, rather than the position of each label.
For the relationship to NMR spectroscopy and application to
heart metabolism, see the following paper: syntactic modeling.
A detailed description of the computer simulation can be found in
the following paper: syntax - the program . For a PowerPoint
slideshow containing explanations of features of the syntactic
modeling approach, click here: Syntactic Model: Slides
The application of the syntactic approach for the testing of
algebraic formulas used to calculate metabolic rates can be
found in the following papers: heart CAC and anaplerosis.
>> Brain Metabolism: There are several aspects that we
investigated. First, on the basis of the analysis of atomic flow in
the citric acid cycle and the metabolic pathways in the brain, we
argued that the gradual reduction in the activity in a single
enzyme (with age or with disease) would suffice to limit the
production of energy in the cerebral neurons. Glutamine
synthetase, primarily a glial enzyme, was one of two enzymes
whose activities were found to be decreased in the postmortem
brains of patients with Alzheimer's disease compared to
nonaffected aged individuals. Inhibition of this enzyme would
necessarily impair neuronal energy production. See the specific
paper (inhibition of glutamine synthetase)-as well as the review
article concerning the relationship of aging, Alzheimer's disease
and metabolic changes (such as diabetes) (aging, metabolism
and Alzheimer's disease).
A second major area of our investigation concerned the use of
stable isotopes (non-radioactive isotopes) to measure rates of
metabolism in the brain. We developed a new method for
estimation of cerebral glucose metabolism (CMRgluc) using in
vivo nuclear magnetic resonance spectroscopy (measuring
cerebral metabolic rates with 13C NMR). We did additional
studies with a metabolic inhibitor which we showed to be
protective to brain metabolism during ischemic attacks
(protection by 2-deoxyglucose in cerebral ischemia).
A third major study concerned the source of nitrogen atom used
to synthesize compounds in the brain (glutamate, glutamine, etc).
This study investigated the importance of leucine as a nitrogen
carrier (leucine-nitrogen metabolism).
>> Heart metabolism: We performed experimental studies in the
isolated, working rat heart and found the lack of a complete
cycling in glutamate-glutamine (glutamine cycling and
corrigendum). In addition, we investigated current methods for
estimating the rate of the pentose phosphate pathway in heart
(pentose phosphate pathway and letter).
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Overview
Our goal is to bring the convenience, elegance and brevity of
mathematical analysis (supported by computer programming) to
the task of understanding the complexity of biological systems.
Our goal is to bring the convenience, elegance and brevity of
mathematical analysis (supported by computer programming) to
the task of understanding the complexity of biological systems.