Design of glycolysis

Abstract

The design of the glycolytic pathway resulting from the continuous refinement of evolution is discussed with regard to three aspects. 1. Functional and structural properties of individual enzymes. The catalytic constants of the glycolytic enzymes are remarkably optimized; the turnover numbers are within one order of magnitude. The same is true for the molarities of catalytic centres in the cytosol, as is noted for yeast. Functional properties of the enzymes are reflected in their tertiary and quaternary structures. 2. Regulatory mechanisms of single enzymes. A classification of the various types of enzymic control mechanisms operating in the glycolytic pathway is given. In addition to the usual Michaelis-Menten saturation kinetics and the various types of inhibition there is control by positive and negative effectors based on oligomeric structures (fast acting, fine control) as well as regulation by chemical interconversion structures (fast acting, fine control) as well as regulation by chemical based on enzymes cascades (slow acting, very effective). 3. Functional and regulatory mechanisms of the whole glycolytic reaction pathway. A prominent feature is the high enzyme:substrate ratio, which guarantees fast response times. However, a quantitative treatment of the overall kinetics is limited by an incomplete knowledge of the enzymes' dynamic and chemical compartmentation as well as some of their control properties. From an analysis of the oscillatory state, certain control points in the glycolytic chain can be located that coincide with major branching points to other metabolic pathways. These points are controlled by fast-acting cooperative enzymes that operate in a flip-flop mechanism together with the respective antagonistic enzymes, preventing futile cycles. The gating enzymes leading to the glycogen store and the citric acid cycle are of the slow-acting but very effective interconvertible type. The combination of all the complex and intricate features of design yields a glycolytic network that enables the cell to respond to its various metabolic needs quickly, effectively and economically.

Population Size Drives Industrial Saccharomyces cerevisiae Alcoholic Fermentation and Is under Genetic Control

“…This is usually thought to be the main parameter that controls the fermentation kinetics of the whole population. In this context, several works searched for the factors controlling the glycolytic flux: in particular, hexose transport and some glycolytic enzymes such as phosphofructokinase or pyruvate kinase have been suggested to be rate-limiting steps of glycolysis, through in vivo and/or in silico analyses (10,15,20,25,49). Increasing these factors was intuitively supposed to increase the glycolytic flux and, therefore, the global fermentative ability that was exploited for industrial purposes (46).…”

Oxygen Breathing Affects 3′-Deoxy-3′-18F-Fluorothymidine Uptake in Mouse Models of Arthritis and Cancer

“…Consequently, reduced breathing frequency due to oxygen breathing and anesthesia may compromise CO 2 elimination and lead to respiratory acidosis. Respiratory acidosis leads, in turn, to cellular acidification, which is a powerful inhibitor of glycolysis (21) and is therefore expected to inhibit cell proliferation (22)(23)(24)(25). To test this hypothesis, we used ketamine and xylazine anesthesia and analyzed pCO 2 , pH, and lactate values in blood samples that were obtained from the retrobulbar venous plexus before 18 F-FLT administration and at the end of PET investigation (Supplemental Fig.…”

“…Because blood pO 2 is an important regulator of breathing (19), breathing oxygen may reduce respiratory drive, which may in turn reduce CO 2 elimination and thus facilitate the development of respiratory acidosis. Acidosis interferes with glycolysis (20,21), and this might play a role in reducing inflammatory and tumor cell proliferation (22)(23)(24)(25). To test this hypothesis, we sought to identify potential respiratory acidosis in mice under ketamine and xylazine anesthesia by analyzing pH, pCO 2 , and lactate values in blood samples that were obtained from the retrobulbar venous plexus (as indicated in Figs.…”

“…Impaired glycolysis is expected to affect lactate formation (21). Therefore, blood samples were obtained as described previously (Figs.…”

Mck1, a member of the glycogen synthase kinase 3 family of protein kinases, is a negative regulator of pyruvate kinase in the yeast Saccharomyces cerevisiae

“…In summary, our findings indicate that Mck1 negatively regulates Pyk1 activity, possibly by direct phosphorylation, and suggest that many of the phenotypes of mck1⌬ mutants may be explained by the hyperactivity of Pyk1. Because pyruvate kinase catalyzes the third irreversible reaction in glycolysis and thus controls, in part, the output of this pathway in both yeast and mammalian cells (3,8,11,19), increased pyruvate kinase activity may stimulate the rate of utilization of glucose 6-phosphate, leading to a reduced capacity for glycogen accumulation. The glycogendeficient phenotype of mck1⌬ mutants could thus arise from the hyperactivation of Pyk1.…”