Abstract
The effect of variation of the rate of input of material on the transient behaviour of metabolic pathways is examined. This reveals the existence of three transient times which make up the overall pathway transient. Two of these have been described previously and represent the times required for the accumulation of the free intermediate pool and the pool of enzyme-bound intermediate. They are state functions and as such are independent of the way in which the steady state was reached. The third is attributable to the variation in the rate of input of material to the pathway. It is dependent on three further factors. These are (a) the time required for the initial enzyme to reach its own steady state, (b) substrate depletion and (c) feedback. The description of the transient is: (Formula: see text) where V0 represents the rate of input and Vss represents the steady-state flux. The transient time associated with the transition between steady-states is shown to be a simple function of the transients for the establishment of each steady state from rest and may be expressed as: tau = tau b-Va/Vb . tau a where Va and Vb refer to the fluxes in the two steady states and tau a and tau b represent the transient times for the establishment of each of the steady-states from rest. The total pathway transient may now be completely defined as: (formula: see text) where summation over all intermediates, I, is implied. The significance of this to the analysis of pathway behaviour is discussed with more general examples of pathway transient analysis.
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- Bryce C. F., Williams D. C., John R. A., Fasella P. The anomalous kinetics of coupled aspartate aminotransferase and malate dehydrogenase. Evidence for compartmentation of oxaloacetate. Biochem J. 1976 Mar 1;153(3):571–577. doi: 10.1042/bj1530571. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chiu C. S., Cook K. S., Greenberg G. R. Characteristics of a bacteriophage T4-induced complex synthesizing deoxyribonucleotides. J Biol Chem. 1982 Dec 25;257(24):15087–15097. [PubMed] [Google Scholar]
- Christopherson R. I., Jones M. E. The overall synthesis of L-5,6-dihydroorotate by multienzymatic protein pyr1-3 from hamster cells. Kinetic studies, substrate channeling, and the effects of inhibitors. J Biol Chem. 1980 Dec 10;255(23):11381–11395. [PubMed] [Google Scholar]
- Cleland W. W. Optimizing coupled enzyme assays. Anal Biochem. 1979 Oct 15;99(1):142–145. doi: 10.1016/0003-2697(79)90055-1. [DOI] [PubMed] [Google Scholar]
- Cook P. F., Wedding R. T. salmonella typhimurium/enzymol. Arch Biochem Biophys. 1977 Jan 15;178(1):293–302. doi: 10.1016/0003-9861(77)90194-1. [DOI] [PubMed] [Google Scholar]
- Duggleby R. G., Sneddon M. K., Morrison J. F. Chorismate mutase-prephenate dehydratase from Escherichia coli: active sites of a bifunctional enzyme. Biochemistry. 1978 Apr 18;17(8):1548–1554. doi: 10.1021/bi00601a030. [DOI] [PubMed] [Google Scholar]
- Easterby J. S. A generalized theory of the transition time for sequential enzyme reactions. Biochem J. 1981 Oct 1;199(1):155–161. doi: 10.1042/bj1990155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Easterby J. S. Coupled enzyme assays: a general expression for the transient. Biochim Biophys Acta. 1973 Feb 15;293(2):552–558. doi: 10.1016/0005-2744(73)90362-8. [DOI] [PubMed] [Google Scholar]
- Easterby J. S. The kinetics of consecutive enzyme reactions. The design of coupled assays and the temporal response of pathways. Biochem J. 1984 May 1;219(3):843–847. doi: 10.1042/bj2190843. [DOI] [PMC free article] [PubMed] [Google Scholar]
- García-Carmona F., García-Cánovas F., Lozano J. A. Optimizing enzyme assays with one or two coupling enzymes. Anal Biochem. 1981 May 15;113(2):286–291. doi: 10.1016/0003-2697(81)90079-8. [DOI] [PubMed] [Google Scholar]
- Harbron S., Woodrow I. E., Kelly G. J., Robinson S. P., Latzko E., Walker D. A. A continuous spectrophotometric assay for sucrose phosphate synthetase. Anal Biochem. 1980 Sep 1;107(1):56–59. doi: 10.1016/0003-2697(80)90491-1. [DOI] [PubMed] [Google Scholar]
- Heinrich R., Rapoport T. A. Mathematical analysis of multienzyme systems. II. Steady state and transient control. Biosystems. 1975 Jul;7(1):130–136. doi: 10.1016/0303-2647(75)90050-7. [DOI] [PubMed] [Google Scholar]
- Hess B., Wurster B. Transient time of the pyruvate kinase-lactate dehydrogenase system of rabbit muscle in vitro. FEBS Lett. 1970 Jul 29;9(2):73–77. doi: 10.1016/0014-5793(70)80316-7. [DOI] [PubMed] [Google Scholar]
- Hijazi N. H., Laidler K. J. Transient-phase and steady-state kinetics for enzyme activation. Can J Biochem. 1973 Jun;51(6):806–814. doi: 10.1139/o73-100. [DOI] [PubMed] [Google Scholar]
- Hijazi N. H., Laidler K. J. Transient-phase and steady-state kinetics for enzyme systems involving two substrates. Can J Biochem. 1973 Jun;51(6):832–840. doi: 10.1139/o73-103. [DOI] [PubMed] [Google Scholar]
- Hijazi N. H., Laidler K. J. Transient-phase and steady-state kinetics for inhibited enzyme systems. I. Single-intermediate mechanisms. Can J Biochem. 1973 Jun;51(6):815–821. doi: 10.1139/o73-101. [DOI] [PubMed] [Google Scholar]
- Hijazi N. H., Laidler K. J. Transient-phase and steady-state kinetics for inhibited enzyme systems. II. Double-intermediate mechanisms. Can J Biochem. 1973 Jun;51(6):822–831. doi: 10.1139/o73-102. [DOI] [PubMed] [Google Scholar]
- Klesov A. A., Grigorash S. Iu. Kineticheski zakonomernosti gidroliza nerastvorimoi tselliulozy pod deistviem polifermentnykh tselliulaznykh sistem v nestatsionarnom rezhime reaktsii. Biokhimiia. 1982 Feb;47(2):240–256. [PubMed] [Google Scholar]
- Kuchel P. W., Roberts D. V. The behaviour of coupled enzyme systems in the transient and steady-state regions of the reaction. Biochim Biophys Acta. 1974 Oct 17;364(2):181–192. doi: 10.1016/0005-2744(74)90002-3. [DOI] [PubMed] [Google Scholar]
- Mally M. I., Grayson D. R., Evans D. R. Catalytic synergy in the multifunctional protein that initiates pyrimidine biosynthesis in Syrian hamster cells. J Biol Chem. 1980 Dec 10;255(23):11372–11380. [PubMed] [Google Scholar]
- Matchett W. H. Indole channeling by tryptophan synthase of neurospora. J Biol Chem. 1974 Jul 10;249(13):4041–4049. [PubMed] [Google Scholar]
- Mattlasson B., Johansson A. C., Mosbach K. Preparation of a soluble, bifunctional enzyme aggregate and studies on its kinetic behaviour in polymer media. Eur J Biochem. 1974 Jul 15;46(2):341–349. doi: 10.1111/j.1432-1033.1974.tb03626.x. [DOI] [PubMed] [Google Scholar]
- McClure W. R. A kinetic analysis of coupled enzyme assays. Biochemistry. 1969 Jul;8(7):2782–2786. doi: 10.1021/bi00835a014. [DOI] [PubMed] [Google Scholar]
- Ovádi J., Keleti T. Kinetic evidence for interaction between aldolase and D-glyceraldehyde-3-phosphate dehydrogenase. Eur J Biochem. 1978 Apr;85(1):157–161. doi: 10.1111/j.1432-1033.1978.tb12223.x. [DOI] [PubMed] [Google Scholar]
- Rapoport T. A., Heinrich R., Jacobasch G., Rapoport S. A linear steady-state treatment of enzymatic chains. A mathematical model of glycolysis of human erythrocytes. Eur J Biochem. 1974 Feb 15;42(1):107–120. doi: 10.1111/j.1432-1033.1974.tb03320.x. [DOI] [PubMed] [Google Scholar]
- Rudolph F. B., Baugher B. W., Beissner R. S. Techniques in coupled enzyme assays. Methods Enzymol. 1979;63:22–42. doi: 10.1016/0076-6879(79)63004-5. [DOI] [PubMed] [Google Scholar]
- Salerno C., Ovádi J., Keleti T., Fasella P. Kinetics of coupled reactions catalyzed by aspartate aminotransferase and glutamate dehydrogenase. Eur J Biochem. 1982 Jan;121(3):511–517. doi: 10.1111/j.1432-1033.1982.tb05816.x. [DOI] [PubMed] [Google Scholar]
- Storer A. C., Cornish-Bowden A. The kinetics of coupled enzyme reactions. Applications to the assay of glucokinase, with glucose 6-phosphate dehydrogenase as coupling enzyme. Biochem J. 1974 Jul;141(1):205–209. doi: 10.1042/bj1410205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Teasdale R. D., Jeffrey P. D., Kuchel P. W., Nichol L. W. Interpretation of the kinetics of consecutive enzyme-catalysed reactions: studies on the arginase-ornithine carbamoyltransferase system. Aust J Biol Sci. 1982;35(2):137–143. doi: 10.1071/bi9820137. [DOI] [PubMed] [Google Scholar]
- Traut T. W. Significance of the enzyme complex that synthesizes UMP in Ehrlich ascites cells. Arch Biochem Biophys. 1980 Apr 1;200(2):590–594. doi: 10.1016/0003-9861(80)90391-4. [DOI] [PubMed] [Google Scholar]
- Welch G. R., Gaertner F. H. Coordinate activation of a multienzyme complex by the first substrate. Evidence for a novel regulatory mechanism in the polyaromatic pathway of Neurospora crassa. Arch Biochem Biophys. 1976 Feb;172(2):476–489. doi: 10.1016/0003-9861(76)90101-6. [DOI] [PubMed] [Google Scholar]
- Welch G. R., Gaertner F. H. Influence of an aggregated multienzyme system on transient time: kinetic evidence for compartmentation by an aromatic-amino-acid synthesizing complex of Neurospora crassa. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4218–4222. doi: 10.1073/pnas.72.11.4218. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Welch G. R. On the free energy "cost of transition" in intermediary metabolic processes and the evolution of cellular infrastructure. J Theor Biol. 1977 Sep 21;68(2):267–291. doi: 10.1016/0022-5193(77)90165-5. [DOI] [PubMed] [Google Scholar]
- Woodrow I. E., Walker D. A. Activation of wheat chloroplast sedoheptulose bisphosphatase: a continuous spectrophotometric assay. Arch Biochem Biophys. 1982 Jul;216(2):416–422. doi: 10.1016/0003-9861(82)90230-2. [DOI] [PubMed] [Google Scholar]
