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Control of flux through the citric acid cycle and the glyoxylate bypass in Escherichia coli.
Biochem Soc Symp. 1987; 54:17-31.BS

Abstract

The glyoxylate bypass and citric acid cycle operate concurrently in Escherichia coli when acetate is the sole source of carbon and energy to sustain aerobic growth. The overall carbon balance allows fluxes through the central metabolic pathways (CMPs) to be computed on the assumption that these metabolic pathways are known. Acetate is fluxed via the CMPs to the precursors required for synthesis of new biomass and also to generate the reducing power and ATP required to convert these precursors to biomass. Under these circumstances, a junction is created at isocitrate where isocitrate lyase (ICL) and isocitrate dehydrogenase (ICDH) compete for their common substrate. In general, flux through ICL generates the precursors used for biosynthesis while the larger part of the flux (95%) through ICDH is dedicated to the supply of reducing power and ATP. The system sustains a large intracellular pool of isocitrate to accommodate the rather low affinity of ICL for this substrate. Excessive flux of isocitrate through ICDH is prevented by regulation of ICDH activity: reversible inactivation of ICDH is achieved by a bifunctional kinase/phosphatase, as the phosphorylated form of ICDH has no activity. The kinase/phosphatase responds to two classes of effectors--intermediates of the CMPs generated by flux through ICL and the lower energy forms of ATP and NADPH (ADP, AMP and NADP+) generated when these intermediates are used for biosynthesis. The effect is to adjust flux through ICDH so that the rate of supply of NADPH and ATP is equal to the demands of biosynthesis. Biosynthetic fluxes are limited by the rate of supply of precursors which depends on flux through ICL. Growth rate is most likely limited by the primary flux of acetate to acetyl-CoA or flux through ICL. In the steady state, the flux through ICDH is regulated to be twice the throughput of ICL. The evolution of this complex pattern of control may have depended on alternatives to the citric acid for energy generation.

Authors+Show Affiliations

Department of Biochemistry, University of Glasgow, Scotland, U. K.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

3332993

Citation

Holms, W H.. "Control of Flux Through the Citric Acid Cycle and the Glyoxylate Bypass in Escherichia Coli." Biochemical Society Symposium, vol. 54, 1987, pp. 17-31.
Holms WH. Control of flux through the citric acid cycle and the glyoxylate bypass in Escherichia coli. Biochem Soc Symp. 1987;54:17-31.
Holms, W. H. (1987). Control of flux through the citric acid cycle and the glyoxylate bypass in Escherichia coli. Biochemical Society Symposium, 54, 17-31.
Holms WH. Control of Flux Through the Citric Acid Cycle and the Glyoxylate Bypass in Escherichia Coli. Biochem Soc Symp. 1987;54:17-31. PubMed PMID: 3332993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Control of flux through the citric acid cycle and the glyoxylate bypass in Escherichia coli. A1 - Holms,W H, PY - 1987/1/1/pubmed PY - 1987/1/1/medline PY - 1987/1/1/entrez SP - 17 EP - 31 JF - Biochemical Society symposium JO - Biochem Soc Symp VL - 54 N2 - The glyoxylate bypass and citric acid cycle operate concurrently in Escherichia coli when acetate is the sole source of carbon and energy to sustain aerobic growth. The overall carbon balance allows fluxes through the central metabolic pathways (CMPs) to be computed on the assumption that these metabolic pathways are known. Acetate is fluxed via the CMPs to the precursors required for synthesis of new biomass and also to generate the reducing power and ATP required to convert these precursors to biomass. Under these circumstances, a junction is created at isocitrate where isocitrate lyase (ICL) and isocitrate dehydrogenase (ICDH) compete for their common substrate. In general, flux through ICL generates the precursors used for biosynthesis while the larger part of the flux (95%) through ICDH is dedicated to the supply of reducing power and ATP. The system sustains a large intracellular pool of isocitrate to accommodate the rather low affinity of ICL for this substrate. Excessive flux of isocitrate through ICDH is prevented by regulation of ICDH activity: reversible inactivation of ICDH is achieved by a bifunctional kinase/phosphatase, as the phosphorylated form of ICDH has no activity. The kinase/phosphatase responds to two classes of effectors--intermediates of the CMPs generated by flux through ICL and the lower energy forms of ATP and NADPH (ADP, AMP and NADP+) generated when these intermediates are used for biosynthesis. The effect is to adjust flux through ICDH so that the rate of supply of NADPH and ATP is equal to the demands of biosynthesis. Biosynthetic fluxes are limited by the rate of supply of precursors which depends on flux through ICL. Growth rate is most likely limited by the primary flux of acetate to acetyl-CoA or flux through ICL. In the steady state, the flux through ICDH is regulated to be twice the throughput of ICL. The evolution of this complex pattern of control may have depended on alternatives to the citric acid for energy generation. SN - 0067-8694 UR - https://www.unboundmedicine.com/medline/citation/3332993/Control_of_flux_through_the_citric_acid_cycle_and_the_glyoxylate_bypass_in_Escherichia_coli_ L2 - https://www.lens.org/lens/search/patent/list?q=citation_id:3332993 DB - PRIME DP - Unbound Medicine ER -