Showing papers by "University of Oxford published in 1985"

Homeostasis model assessment : insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man

Abstract: The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.

The Negative Priming Effect: Inhibitory Priming by Ignored Objects:

Abstract: A priming paradigm was employed to investigate the processing of an ignored object during selection of an attended object. Two issues were investigated: the level of internal representation achieved for the ignored object, and the subsequent fate of this representation. In Experiment 1 a prime display containing two superimposed objects was briefly presented. One second later a probe display was presented containing an object to be named. If the ignored object in the prime display was the same as the subsequent probe, naming latencies were impaired. This effect is termed negative priming. It suggests that internal representations of the ignored object may become associated with inhibition during selection. Thus, selection of a subsequent probe object requiring these inhibited representations is delayed. Experiment 2 replicated the negative priming effect with a shorter inter-stimulus interval. Experiment 3 examined the priming effects of both the ignored and the selected objects. The effect of both identi...

Anti Self‐Dual Yang‐Mills Connections Over Complex Algebraic Surfaces and Stable Vector Bundles

Abstract: On presente une correspondance entre la geometrie algebrique et la geometrie differentielle des fibres vectoriels. Soit une surface algebrique projective X qui a un plongement donne X≤CP N et soit ω une metrique de Kahler sur X dont la classe de cohomologie associee est duale a la classe de section d'hyperplan [H]. Un fibre sur X est stable, par rapport au plongement projectif, si et seulement si il admet une connexion irreductible d'Hermite-Einstein par rapport a la metrique ω. Cette connexion est alors unique

Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG.

Abstract: Rheumatoid arthritis (RA) is a widely prevalent (1-3%) chronic systemic disease thought to have an autoimmune component; both humoral and cellular mechanisms have been implicated. Primary osteoarthritis (OA) is considered to be distinct from rheumatoid arthritis, and here damage is thought to be secondary to cartilage degeneration. In rheumatoid arthritis, immune complexes are present that consist exclusively of immunoglobulin, implying that this is both the 'antibody' (rheumatoid factor [RF]) and the 'antigen' (most commonly IgG). Autoantigenic reactivity has been localized to the constant-region (C gamma 2) domains of IgG. There is no evidence for a polypeptide determinant but carbohydrate changes have been reported. We have therefore conducted a study, simultaneously in Oxford and Tokyo, to compare in detail the N-glycosylation pattern of serum IgG (Fig. 1) isolated from normal individuals and from patients with either primary osteoarthritis or rheumatoid arthritis. The results, which required an evaluation of the primary sequences of approximately 1,400 oligosaccharides from 46 IgG samples, indicate that: (1) IgG isolated from normal individuals, patients with RA and patients with OA contains different distributions of asparagine-linked bi-antennary complex-type oligosaccharide structures, (2) in neither disease is the IgG associated with novel oligosaccharide structures, but the observed differences are due to changes in the relative extent of galactosylation compared with normal individuals. This change results in a 'shift' in the population of IgG molecules towards those carrying complex oligosaccharides, one or both of whose arms terminate in N-acetylglucosamine. These two arthritides may therefore be glycosylation diseases, reflecting changes in the intracellular processing, or post-secretory degradation of N-linked oligosaccharides.

Loop groups and equations of KdV type

Abstract: On decrit une construction qui attribue une solution de l'equation de Korteweg-de Vries a chaque point d'un certain grassmannien de dimension infinie. On determine quelle classe on obtient par cette methode

A Model of Cardiac Electrical Activity Incorporating Ionic Pumps and Concentration Changes

Abstract: Equations have been developed to describe cardiac action potentials and pacemaker activity. The model takes account of extensive developments in experimental work since the formulation of the M.N.T. (R. E. McAllister, D. Noble and R. W. Tsien, J. Physiol., Lond. 251, 1-59 (1975)) and B.R. (G. W. Beeler and H. Reuter, J. Physiol., Lond. 268, 177-210 (1977)) equations. The current mechanism i $\_{K2}$ has been replaced by the hyperpolarizing-activated current, i $\_f$ . Depletion and accumulation of potassium ions in the extracellular space are represented either by partial differential equations for diffusion in cylindrical or spherical preparations or, when such accuracy is not essential, by a three-compartment model in which the extracellular concentration in the intercellular space is uniform. The description of the delayed K current, i $\_K$ , remains based on the work of D. Noble and R. W. Tsien (J. Physiol., Lond. 200, 205-231 (1969a)). The instantaneous inward-rectifier, i $\_{K1}$ , is based on S. Hagiwara and K. Takahashi's equation (J. Membrane Biol. 18, 61-80 (1974)) and on the patch clamp studies of B. Sakmann and G. Trube (J. Physiol., Lond. 347, 641-658 (1984)) and of Y. Momose, G. Szabo and W. R. Giles (Biophys. J. 41, 311a (1983)). The equations successfully account for all the properties formerly attributed to i $\_{K2}$ , as well as giving more complete descriptions of i $\_{K1}$ and i $\_K$ . The sodium current equations are based on experimental data of T. J. Colatsky (J. Physiol., Lond. 305, 215-234 (1980)) and A. M. Brown, K. S. Lee and T. Powell (J. Physiol., Lond. 318, 479-500 (1981)). The equations correctly reproduce the range and magnitude of the sodium \`window' current. The second inward current is based in part on the data of H. Reuter and H. Scholz (J. Physiol., Lond. 264, 17-47 (1977)) and K. S. Lee and R. W. Tsien (Nature, Lond. 297, 498-501 (1982)) so far as the ion selectivity is concerned. However, the activation and inactivation gating kinetics have been greatly speeded up to reproduce the very much faster currents recorded in recent work. A major consequence of this change is that Ca current inactivation mostly occurs very early in the action potential plateau. The sodium-potassium exchange pump equations are based on data reported by D. C. Gadsby (Proc. natn. Acad. Sci. U.S.A. 77, 4035-4039 (1980)) and by D. A. Eisner and W. J. Lederer (J. Physiol., Lond. 303, 441-474 (1980)). The sodium-calcium exchange current is based on L. J. Mullins' equations (J. gen. Physiol. 70, 681-695 (1977)). Intracellular calcium sequestration is represented by simple equations for uptake into a reticulum store which then reprimes a release store. The repriming equations use the data of W. R. Gibbons & H. A. Fozzard (J. gen. Physiol. 65, 367-384 (1975b)). Following Fabiato & Fabiato's work (J. Physiol., Lond. 249, 469-495 (1975)), Ca release is assumed to be triggered by intracellular free calcium. The equations reproduce the essential features of intracellular free calcium transients as measured with aequorin. The explanatory range of the model entirely includes and greatly extends that of the M.N.T. equations. Despite the major changes made, the overall time-course of the conductance changes to potassium ions strongly resembles that of the M.N.T. model. There are however important differences in the time courses of Na and Ca conductance changes. The Na conductance now includes a component due to the hyperpolarizing-activated current, i $\_f$ , which slowly increases during the pacemaker depolarization. The Ca conductance changes are very much faster than in the M.N.T. model so that in action potentials longer than about 50 ms the primary contribution of the fast gated calcium channel to the plateau is due to a steady-state \`window' current or non-inactivated component. Slower calcium or Ca-activated currents, such as the Na-Ca exchange current, or Ca-gated currents, or a much slower Ca channel must then play the dynamic role previously attributed to the kinetics of a single type of calcium channel. This feature of the model in turn means that the repolarization process should be related to the inotropic state, as indicated by experimental work. The model successfully reproduces intracellular sodium concentration changes produced by variations in [Na] $\_o$ , or Na-K pump block. The sodium dependence of the overshoot potential is well reproduced despite the fact that steady state intracellular Na is proportional to extracellular Na, as in the experimental results of D. Ellis J. Physiol., Lond. 274, 211-240 (1977)). The model reproduces the responses to current pulses applied during the plateau and pacemaker phases. In particular, a substantial net decrease in conductance is predicted during the pacemaker depolarization despite the fact that the controlling process is an increase in conductance for the hyperpolarizing-activated current. The immediate effects of changing extracellular [K] are reproduced, including: (i) the shortening of action potential duration and suppression of pacemaker activity at high [K]; (ii) the increased automaticity at moderately low [K]; and (iii) the depolarization to the plateau range with premature depolarizations and low voltage oscillations at very low [K]. The ionic currents attributed to changes in Na-K pump activity are well reproduced. It is shown that the apparent K $\_m$ for K activation of the pump depends strongly on the size of the restricted extracellular space. With a 30% space (as in canine Purkinje fibres) the apparent K $\_m$ is close to the assumed real value of 1 mM. When the extracellular space is reduced to below 5%, the apparent K $\_m$ increases by up to an order of magnitude. A substantial part of the pump is then not available for inhibition by low [K] $\_b$ . These results can explain the apparent discrepancies in the literature concerning the K $\_m$ for pump activation.

Life history variation in primates.

Abstract: Extensive variation in life-history patterns is documented across primate species. Variables included are gestation length, neonatal weight, litter size, age at weaning, age at sexual maturity, age at first breeding, longevity, and length of the estrous cycle. Species within genera and genera within subfamilies tend to be very similar on most measures, and about 85% of the variation remains when the subfamily is used as the level for statistical analysis. Variation in most life-history measures is highly correlated with variation in body size, and differences in body size are associated with differences in behavior and ecology. Allometric relationships between life-history variables and adult body weight are described; subfamily deviations from best-fit lines do not reveal strong correlations with behavior or ecology. However, for their body size, some subfamilies show consistently fast development across life-history stages while others are characteristically slow. One exception to the tendency for relative values to be positively correlated is brain growth: those primates with relatively large brains at birth have relatively less postnatal brain growth. Humans are a notable exception, with large brains at birth and high postnatal brain growth.

Associations across time: the hippocampus as a temporary memory store

Abstract: All recent memory theories of hippocampal function have incorporated the idea that the hippocampus is required to process items only of some qualitatively specifiahle kind, and is not required to process items of some complementary set. In contrast, it is now proposed that the hippocampus is needed to process stimuli of all kinds, but only when there is a need to associate those stimuli with other events that are temporally discontiguous. In order to form or use temporally discontiguous associations, it is essential to maintain some memory of the first component until the second component has occurred. When the temporal gap to he spanned is small, and the number of items to be temporarily retained is low, a limited-capacity, short-term store is sufficient to allow associations to be formed. Such a store is presumed to operate in parallel with the hippocampus in normal animals. Hippocampal damage disrupts a much higher-capacity store that has a slower decay rate, and so leaves animals with only a very limited ability to form temporally discontiguous associations. Hippocampal damage, however, is not held to affect the long-term storage of associations of any kind, if they can be formed. Analyses of both new and existing data are presented to show that by classifying tasks in terms of the need to use a temporary memory store to retain temporally discontiguous information one can cut right across existing classifications as well as achieve a better fit to the data. The hippocampus thus seems best described as a high-capacity, intermediate-term memory store.

Selective attention and priming: inhibitory and facilitatory effects of ignored primes.

Abstract: The priming effects of ignored information have been studied in Stroop displays (Neill, 1977) and with spatially superimposed drawings (Tipper, in this issue); naming of probes related to ignored primes is delayed in these experiments (“negative priming”). This negative priming effect is confirmed in a list reading task in Experiment 1, which used partially superimposed letters, and Experiment 2, which used spatially separated letters. Furthermore, Lowe (1979) using Stroop colour words observed that changing the nature of the probe such that it did not require selection from a competing word reversed the priming effects of the ignored word from inhibition to facilitation. Experiment 3 confirmed this observation when subjects selected a red letter from a green letter. Two models are suggested to account for this result. In the first, negative priming is a product of the ignored prime and subsequent probe being encoded both as a stimulus to be ignored and one to be named (Allport, Tipper and Chmiel, in pres...

The size and strength of the quadriceps muscles of old and young men

Abstract: The mean isometric strength of the stronger quadriceps muscles of 12 healthy men in their seventies was 39% less than that of 12 healthy men in their twenties (P less than 0.001). The cross-sectional area of the quadriceps was measured at mid-thigh, by ultrasound scanning; the older men's stronger quadriceps were 25% smaller (P less than 0.001). The ratio of the stronger quadriceps' strength to its cross-sectional area was very similar in the old men to values obtained previously for both old and young women, but averaged 19% less than in the young men (P less than 0.02). Quadriceps size and strength were correlated in the old men (r = 0.77, P = 0.03) but not in the young men (r = 0.15). The principal axis of the relationship between quadriceps size and strength in the old men was very similar to those previously reported for both old and young women. The quadriceps strength of some young men is greater than would be expected from the size of the muscle.

Flux-tube model for hadrons in QCD.

Abstract: We extract from the strong-coupling Hamiltonian lattice formulation of QCD a model for hadrons based on the use of quark and flux-tube degrees of freedom. The ordinary quark model of mesons and baryons is recovered as an appropriate limit, but the properties of hybrids, pure glue, and multiquark hadrons are also predicted by the model. The basic tenets of the model can be tested by lattice Monte Carlo simulations.

Grain boundaries in semiconductors

Abstract: This review presents the available experimental and theoretical understanding on the structure and electronic properties of grain boundaries in semiconducting materials. High-resolution electron microscope images of interfaces are interpreted within the framework of the structural unit model of grain boundaries, and the electronic properties of the grain boundaries discussed with relation to the popular symmetric Schottky barrier model for charge trapping and potential barrier formation. It is shown that these models give some limited understanding of the physical processes that occur at grain boundaries in elemental semiconductors, but that in compound semiconducting materials the effects of non-stoichiometry at the boundary regions must also be considered. Segregation of impurity and dopant species to the boundaries can have significant influence on their electrical properties, and the question of what structural or chemical features are responsible for the observed properties is posed. Diffusion at semiconductor grain boundaries is also discussed, and finally the electrical properties of zinc oxide varistor material are presented in the light of the models of carrier interactions with grain boundaries.

Glutamine metabolism in lymphocytes: its biochemical, physiological and clinical importance

Abstract: Glutamine is utilized at a high rate (fourfold higher than that of glucose) by isolated incubated lymphocytes and produces glutamate, aspartate, lactate and ammonia The pathway for glutamine metabolism includes the reactions catalysed by glutaminase, aspartate aminotransferase, oxoglutarate dehydrogenase, succinate dehydrogenase, fumarase, malate dehydrogenase and phosphoenolpyruvate carboxykinase In fact little if any of the carbon of the glutamine that is used is converted to acetyl-CoA for complete oxidation For this reason, the oxidation of glutamine is only partial and, in an analogous manner to the terminology used to describe the partial oxidation of glucose to lactate as glycolysis, the term glutaminolysis is used to describe the process of partial glutamine oxidation The role of glutaminolysis in lymphocytes and perhaps other rapidly dividing cells is to provide both nitrogen and carbon for precursors for synthesis of macromolecules (eg purines and pyrimidines for DNA and RNA) and also energy However, the rate of glutamine utilization by lymphocytes is markedly in excess of the precursor requirements (which are at most 4%) and if glutamine was vitally important in energy production it would be expected that more would be converted to acetyl-CoA for complete oxidation via the Krebs cycle Indeed most of the energy for lymphocytes may be obtained by the complete oxidation of fatty acids and ketone bodies Consequently the role of the high rate of glutaminolysis in lymphocytes and other rapidly dividing cells may be identical to that of glycolysis: the high rates provide ideal conditions for the precise and sensitive control of the rate of use of the intermediates of these pathways for biosynthesis when required High rates of glycolysis and glutaminolysis can be seen as part of a mechanism of control to permit synthesis of macromolecules when required without any need for extracellular signals to make more glucose or glutamine available for these cells In order to maintain a high rate of glutaminolysis despite fluctuation in the plasma level of glutamine, the flux through the glutaminolytic pathway can be controlled and the key processes in the lymphocyte that may play a role in this process include glutamine transport across the cell and mitochondrial membranes, glutaminase and oxoglutarate dehydrogenase Changes in the intracellular concentration of Ca2+ may play a role in control of one or more of these reactions(ABSTRACT TRUNCATED AT 400 WORDS)

An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamine?

Abstract: It has been proposed that three major receptor subtypes subserve the putative transmitter role of glutamate and aspartate in the mammalian central nervous system. One subtype is classified by the specific agonist N-methylaspartate (NMA) and the specific antagonist 4-amino-2-phosphonovaleric acid. It has been shown recently that excitation of neurones by NMA is also selectively reduced by dissociative anaesthetics such as ketamine and phencyclidine and by sigma opiates, drugs of abuse with common psychotomimetic properties. Responses to NMA have an unusual voltage relation which may result from a voltage-dependent block of the activated channel by physiological concentrations of magnesium. No synaptic potential with properties similar to those of responses to NMA, however, has yet been reported. We describe here an excitatory postsynaptic potential (e.p.s.p.) evoked by electrical stimulation of the white matter and recorded intracellularly from pyramidal cells in slices of rat somatosensory cortex. This e.p.s.p. has the appropriate voltage relation and sensitivity to Mg2+ and ketamine to be an NMA receptor-mediated synapse and a potential central site for the psychotomimetic actions of ketamine.

On the relationship of normal modes to local modes in molecular vibrations

Abstract: A simple model for the effective vibrational hamiltonian of the XH stretching vibrations in H2O, NH3 and CH4 is considered, based on a morse potential function for the bond stretches plus potential and kinetic energy coupling between pairs of bond oscillators. It is shown that this model can be set up as a matrix in local mode basis functions, or as a matrix in normal mode basis functions, leading to identical results. The energy levels obtained exhibit normal mode patterns at low vibrational excitation, and local mode patterns at high excitation. When the hamiltonian is set up in the normal mode basis it is shown that Darling-Dennison resonances must be included, and simple relations are found to exist between the xrs , gtt , and Krrss anharmonic constants (where the Darling-Dennison coefficients are denoted K) due to their contributions from morse anharmonicity in the bond stretches. The importance of the Darling-Dennison resonances is stressed. The relationship of the two alternative representations of...

Insulin-like growth factor-II gene expression in Wilms' tumour and embryonic tissues

Abstract: Wilms' tumour (nephroblastoma) is an embryonal neoplasm occurring in hereditary and spontaneous forms. Both types show rearrangements of the short arm of chromosome 11. The germ line of children with the rare inherited triad of aniridia, genitourinary abnormality and mental retardation carry a chromosome 11 that has a deletion in its short arm (band 11p13) and these children are at increased risk of developing Wilms' tumour1,2. Neonates with the Beckwith–Wiedemann syndrome, in which there may be duplication of the 11p13–11p15 region, are similarly predisposed3. In the spontaneous form of the tumour a deletion of the Hp14 band in tumour cells, but not in normal cells, has been reported4, and the development of homozygosity for recessive mutations in the 11p region is implicated in the aetiology of Wilms' tumour5–8. In view of these chromosomal rearrangements and because Wilms' tumour is historically indistinguishable from the early stages of kidney development9, we have now examined the expression of genes localized to 11p in Wilms' tumour and human embryonic tissue. In 12 sporadic tumours examined, the expression of the gene coding for insulin-like growth factor-II (IGF-II), localized to the 11p15 region, was markedly increased relative to adult tissues, but was comparable to the level of expression in several fetal tissues including kidney, liver, adrenals and striated muscle. This may reflect the stage of tumour differentiation, but could also contribute to the malignant process, as IGF-II is an embryonal mitogen10–13.

A behavioural and biochemical study in mice and rats of putative selective agonists and antagonists for 5-HT1 and 5-HT2 receptors.

Abstract: 1 Radioligand binding techniques have demonstrated the existence of 5-hydroxytryptamine (5-HT) binding subtypes: 5-HT2, 5-HT1A and 5-HT1B. These techniques have also indicated that certain drugs appear to show sub-type specificity: 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A agonist; 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)l-H indole (RU 24969), a 5-HT1B agonist; and ritanserin, a 5-HT2 antagonist. (−)−Propranolol is a 5-HT1 antagonist of uncertain sub-type specificity. 2 An examination has been made in mice and rats of the behavioural and biochemical effects of these drugs to determine whether the binding sites have physiological functions and further characterise the behavioural models. 3 Administration of carbidopa (25 mg kg−1) plus 5-hydroxytryptophan (100 mg kg−1) produced head-twitch behaviour in mice which was antagonized by ritanserin (ED50 = 65 μg kg−1) but not (−)−propranolol (20 mg kg−1). 8-OH-DPAT (1–10 mg kg−1 s.c.) and RU 24949 (5 mg kg−1 i.p.) did not produce head-twitch behaviour. 8-OH-DPAT decreased 5-HTP- but not S-methoxy-N-N-dimethyl-tryptamine (5 mg kg−1)-induced head-twitch by a (−)−propranolol-insensitive mechanism. 4 Locomotor activity produced in mice by RU 24969 (3 mg kg−1) was antagonized by (−)−propranolol (20 mg kg−1) but not the (+)-isomer. (−)−Propranolol did not antagonize the behaviour induced in rats. 5 In mice, both 8-OH-DPAT and RU 24969 markedly inhibited whole brain 5-HT synthesis and this effect was not antagonized by (−)−propranolol. 6 In rats, 8-OH-DPAT (3 mg kg−1 s.c.) produced all the behavioural changes seen after quipazine (25 mg kg−1). (−)−Propranolol inhibited the behaviour changes produced by both agonists, while ritanserin antagonized the behaviour produced by quipazine but not 8-OH-DPAT. It is concluded, therefore, that the 5-HT1A receptor exists between the 5-HT2 receptor and the behavioural effectors. 7 8-OH-DPAT (at 20°C ambient temperature) rapidly decreased rat body temperature, an effect antagonized by (−)−propranolol but not ritanserin. Quipazine (at 27°C ambient temperature, but not 20°C) increased body temperature but the effect was not blocked by either antagonist. 8 Ritanserin does not antagonize apomorphine-induced locomotion in either species. 9 We suggest that 5-HT-induced head-twitch behaviour in mice is a useful 5-HT2 receptor model and the temperature change following 8-OH-DPAT injection in rats may be a 5-HT1A model. While (−)−propranolol antagonizes 8-OH-DPAT effects in rat, it does not inhibit 8-OH-DPAT effects in mice, and instead antagonizes RU 24969-induced locomotion. Its status as a 5-HT1 antagonist remains ill-defined.

The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells

Abstract: The rates of utilization of both glucose and glutamine are high in rapidly dividing ceils such as enterocytes, lymphocytes, thymocytes, tumour cells; the oxidation of both glucose and glutamine is only partial, glucose to lactate and glutamine to glutamate , alanine or aspartate ; and these partial processes are termed glycolysis and glutaminolysis respectively . Both processes generate energy and also provide precursors for important biosynthetic processes in such cells. However, the rates of utilization of precursors for macromolecular biosynthesis are very low in comparison to the rates oi partial oxidation, and energy generation per se may not be the correct explanation for high rates of glycolysis and glutaminolysis in these cells since oxidation is only partial and other fuels can be used to generate energy. Both the high fluxes and the metabolic characteristics of these two processes can be explained by application of quantitative principles of control as applied to branched metabolic pathway s (Crabtree & Newsholme, 1985). If the flux through one branch is greatly in excess of the other, then the sensitivity of the flux of the low-flux pathway to regulators is very high. Hence, it is suggested that, in rapidly dividing ceils, high rates of glycolysis and gtutaminolysis are required not for energy or precursor provision per se but for high sensitivity of the pathways involved in the use of precursors for macromolecular synthesis to specific regulators to permithigh rates of proliferation when required for example, in lymphocytes in response to a massive infection.