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Does [ATP] in the cell change?

Michael Kohn kohn at VALIANT.NIEHS.NIH.GOV
Wed Mar 31 12:59:12 EST 1999


Resolution of questions like this is one of the great triumphs of
computer simulation of metabolism. So much emphasis is placed on
describing steady states that students are led to think that such
states are the normal situation inside the cell. Indeed, the
biochemical machinery is often readjusting concentrations of metabolic
intermediates and co-factors to generate the fluxes required by the
external demands on the cell. These demands can be derived from changes
in work load (muscle), extracellular ion concentrations (excitable
tissues), or merely change in exogenous substrate.

Ascites tumnor cells in a substrate-free medium have 3.2 mM ATP. Add
12.5 mM glucose to the medium and the cell hyerpolarizes (K+ falls from
123 mM to 97.7 mM and Na+ rises from 38.4 mM to 621.3 mM). ATP falls to
2.3 mM. Part of this fall is due to conversion to ADP (0.625 to 0.724
mM) and the rest to AMP. Similar metabolic rearrangements have been
found in perfused rat heart suddenly given glucose as an exogenous
substrate. Muscle subjected to a suddenly increased work load
transiently loses ATP because metabolism of endogenous fuels (e.g.
pyruvate, citrate, glycogen, triglycerides) is insufficient to maintain
ATP synthesis at a rate sufficient to meet the energy demand until
delivery of exogenous substrate becomes fast enough to sustain the work
load. A similar situation applies to the NAD/NADH couple.

-- 
Michael C. Kohn

Laboratory of Computational Biology and Risk Analysis
National Institute of Environmental Health Sciences
P.O. Box 12233, Mail Drop A3-06
Research Triangle Park, NC 27709-2233

Telephone:
919-541-4929 (voice)
919-541-1479 (fax)

e-mail:
kohn at valiant.niehs.nih.gov

Web site:
http://valiant.niehs.nih.gov



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