Yeast cells, glycolytic oscillations

M. Bier, B. M. Bakker, and H. V. Westerhoff, How yeast cells synchronize their glycolytic oscillations A perturbation analytic treatment. Biophys. J. 78, 1087 1093 (2000). 

Glycolytic oscillations in yeast cells provided one of the first examples of oscillatory behavior in a biochemical system. They continue to serve as a prototype for cellular rhythms. This oscillatory phenomenon, discovered some 40 years ago [36, 37] and still vigorously investigated today [38], was important in several respects First, it illustrated the occurrence of periodic behavior in a key metabolic pathway. Second, because they were soon observed in cell extracts, glycolytic oscillations provided an instance of a biochemical clock amenable to in vitro studies. Initially observed in yeast cells and extracts, glycolytic oscillations were later observed in muscle cells and evidence exists for their occurrence in pancreatic p-cells in which they could underlie the pulsatile secretion of insulin [39]. 

The question of how glycolytic oscillations synchronize in a population of yeast cells is of great current interest [51]. It has long been known that the oscillations disappear in a yeast suspension when the cell density decreases below a critical value. Acetaldehyde appears to act as synchronizing factor in such suspensions [52], and the way it allows cells to synchronize is being... 

The three best-known examples of biochemical oscillations were found during the decade 1965-1975 [40,41]. These include the peroxidase reaction, glycolytic oscillations in yeast and muscle, and the pulsatile release of cAMP signals in Dictyostelium amoebae (see Section V). Another decade passed before the development of Ca " " fluorescent probes led to the discovery of oscillations in intracellular Ca +. Oscillations in cytosolic Ca " " have since been found in a variety of cells where they can arise spontaneously, or after stimulation by hormones or neurotransmitters. Their period can range from seconds to minutes, depending on the cell type [56]. The oscillations are often accompanied by propagation of intracellular or intercellular Ca " " waves. The importance of Ca + oscillations and waves stems from the major role played by this ion in the control of many key cellular processes—for example, gene expression or neurotransmitter secretion. 

J. Higgins, A chemical mechanism for oscillation of glycolytic intermediates in yeast cells. Pwc. Natl. Acad. Sci. USA 51, 989-994 (1964). 

P. Richard, B. M. Bakker, B. Teusink, K. Van Dam, H. V. Westerhoff, Acetaldehyde mediates the synchronization of sustained glycolytic oscillations in populations of yeast cells. Eur. 

IIIF) 1964 Gosh, A., Chance, B. Oscillations of Glycolytic Intermediates in Yeast Cells, Biochem. Biophys. Res. Commun. vol. 16, 174-181... 

IIIF) 1964 Higgins, J. A Chemical Mechanism for Oscillations of Glycolytic Intermediates in Yeast Cells, Proc. N.A.S. (USA) vol. 51, 989-994... 

Dealt with in turn are (i) glycolytic oscillations that occur in yeast and muscle cells, with a period of several minutes (ii) oscillations of cyclic AMP (cAMP) that govern with a similar period the transition from the unicellular to the multicellular stage in the life cycle of Dictyostelium amoebae (iii) intracellular Ca oscillations, which occur with a period ranging from seconds to minutes in many cell types, either spontaneously or after stimulation by a hormone or a neurotransmitter ... 

The oscillations observed in vitro in the glycolytic system of muscle (Frenkel, 1968 Tomheim Lowenstein, 1974, 1975) and yeast cells (Pye Chance, 1966 Hess Boiteux, 1968a,b, 1971 Hess, Boiteux Kruger, 1969 Pye, 1969, 1971) are still the prototype for biochemical oscillations resulting from the regulation of enzyme activity. These peri-... 

Fig. 2.1. Damped oscillations in the fluorescence of a glycolytic intermediate, NADH, following the injection of glucose (right) in a suspension of yeast cells. This observation was the first indication of the possibility of oscillatory behaviour in glycolysis. The curve on the left shows the addition of ethanol, an, anaerobic condition (Duysens Amesz, 1957).

Betz Moore, 1967 Betz Sel kov, 1969 Hess et al, 1969) or following changes in pH (Hess et al., 1969 Hocker et al, 1994). Yeast cells undergoing glycolytic oscillations rapidly synchronize in stirred suspensions (Ghosh, Chance Pye, 1971). The synchronizing factor... 

The essential property of glycolytic oscillations is illustrated by fig. 2.4a and b as well as table 2.1 sustained periodic behaviour is observed only in a precise range of substrate injection rates. This observation, carried out in yeast extracts (Hess Boiteux, 1968b, 1973 Hess et al, 1969), was confirmed (Von Klitzing Betz, 1970) in suspensions of intact yeast cells (fig. 2.5). Below a critical value of the substrate injection rate, the system reaches a stable steady state. When this rate increases, oscillations occur, but they disappear when the substrate injection rate exceeds a second, higher, critical value. This disappearance is reversible, as shown by fig. 2.4b. The period of glycolytic oscillations is of the order of several minutes and diminishes as the substrate injection rate increases (Hess et al, 1969 Hess Boiteux, 1973 see table 2.1). 

Fig. 2.5. Influence of the substrate injection rate on glycolytic oscillations in a suspension of intact yeast cells. The successive decrements in the glucose injection rate cause the progressive lengthening of the period (Von Klitzing Betz, 1970).

Besides yeast and muscle, glycolytic oscillations have also been observed in Ehrlich ascites tumour cells (Ibsen Schiller, 1967) an insect, the blowfly Phormia terraenovae, for which age-dependent changes in the oscillations have been described (Collatz Horning, 1990 Horning Collatz, 1990) pancreatic p-cells (Chou et al., 1992) and, very recently, heart cells (O Rourke et al., 1994). 

Aon, M.A., S. Cortassa, H.V. Westerhoff K. Van Dam. 1992. Sjmchrony and mutual stimulation of yeast cells during fast glycolytic oscillations. J. Gen. Microbiol. 138 2219-27. 

Glycolytic oscillations are the best-known examples of metabolic oscillations. Glycolysis occurs in yeast cells, cell-free extracts, beef-heart extracts, rat skeletal-muscle extracts and tumour cells. Several reviews on the subject have appeared in the literature [18-22]. 

Whereas oscillatory phenomena have been, until recently, considered chemical curiosities, they had been of great interest to biochemists for years. Metabolic pathways conform to all requirements for the observation of oscillations the systems are open—reactants constantly enter across cell walls and products are removed they are far from equilibrium there are feedback loops to maintain and reassert control even when the cell is drastically perturbed. Most biochemical oscillators are so complex that a detailed mechanistic analysis, such as that given for the Belousov reaction, is not available. The mechanism of glycolytic oscillation in yeast is the most well established. 

Flenson, M.A., Muller, D., and Reuss, M. (2002) Cell population modelling of yeast glycolytic oscillations. Biochem. J, 368,433-581. 

Studies with yeast, heart, and brain have shown that concentrations of intermediates within the glycolytic pathway often follow an oscillating function. Continuous spectrophotometric recording techniques for determining the NAD" /NADH ratio in cell-free extracts first revealed oscillations of the NADH level in these systems. These studies then led to the discovery of glycolytic oscillations in yeast cell and cell-free extracts, beef heart extracts, rat skeletal muscle extracts, and in ascites tumor cells, with concentrations of intermediates varying in the range between 10 and 10 M (Chance et al., 1973). 

Glycolytic oscillations in yeast have been known for a long time (for review see reference [67]). The fact that sustained oscillations can be observed in a population, implies that some synchronisation mechanisms prevents the cells... 

This will be illustrated in the following example. Sustained oscillations of glycolytic intermediates have been shown in the yeast S. cerevisiae, both in cell free extracts [64, 65] and in whole cell cultures [63, 66]. Oscillatory growth is also a well-documented phenomenon in this yeast (see reference [16]) for further references). In the latter case, there may be an oscillatory shift in proportion of the respiratory and fermentative catabolism, during continuous aerobic growth on glucose. The oscillatory behaviour has been documented as an oscillation of substrate consumption rates and product formation rates rather than as an oscillation of metabolic intermediates [16]. An oscillatory behaviour may be of short (duration less than 1 min. [62, 63, 66]), medium (duration less than 1 hour [64]), or long term duration (duration of several days [16] ). 

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