Glycolytic Sequence Research Articles

Targeting Aberrantly Activated Glycolysis in Natural Killer T Cell Lymphomas

Background and aims: With advances in the diagnosis and treatment of malignant lymphoma, improvements in long-term survival have been achieved for most common lymphoma types. However, natural killer/T-cell lymphoma (NKTL), which is rare in Europe and North America (0.3%) but relatively common in Asia and Latin America, has been left behind as a subtype of lymphoma with a high relapse rate and a poor prognosis. In particular, the outcome of patients with advanced or recurrent NKTL is dismal, with an overall survival of only a few months. This is mainly attributed to the intrinsic resistance of NKTL cells to anthracycline due to the high expression of P-glycoprotein. Molecular-targeted drugs used for other hematological malignancies, such as anti-CD30 and anti-CD52 monoclonal antibodies, have only limited effects on NKTL, and conversely, these drugs can cause severe immunodeficiency and severe autoimmune diseases, often with a fatal course. The development of NKTL-specific and effective molecular-target therapies is expected to improve the prognosis of NKTL. Methods: We performed a gene expression array targeting genes involved in glucose cell metabolism to compare the gene signatures of NK cell lines (NKL, NK92, YT, and KYHG1) and freshly isolated NK cells from three healthy donors (FNK). Results: The expression of various glucose metabolism genes was higher in NK cell lines than in FNK cells, and in particular, the PKM gene was highly enriched in NK cell lines. The PKM gene encodes the pyruvate kinase muscle isozyme 2 (PKM2), which is responsible for ATP production within the glycolytic sequence and plays an essential role in aerobic glycolysis (the Warburg effect), a dominant metabolic pathway used by cancer cells. Immunohistochemistry studies revealed high PKM2 protein expression in 17 out of 20 tumor tissues derived from patients with extranodal NK/T cell lymphoma. Treatment of NKL, NK92, YT, and KYHG1 cells with Benserazide or Shikonin, two known PKM2 inhibitors, robustly induced cell apoptosis in a time- and dose-dependent manner and inhibited colony formation in in vitro clonogenic assays. Western blotting studies showed a dose-dependent inhibition of STAT1 and STAT3 in NK cell lines exposed to PKM2 inhibitors. A colorimetric assay showed that PKM2 glycolytic activity correlated with the PKM2 gene expression in NK cells, with significantly higher glycolytic activity in malignant NK cell lines than in normal FNK cells. Further mechanistic studies showed that in normal FNK cells, PKM2 is mainly in the tetrameric form, where glucose is converted to pyruvate to generate ATP. In contrast, in malignant NK cell lines, PKM2 is mainly expressed in its dimeric form, with a low affinity for pyruvate and a higher affinity for glycolytic intermediates that promote the synthetic processes and thereby lead to persistent cell proliferation. Conclusions: These results substantiate the importance of aerobic glycolysis in malignat NK cells and indicate that targeting this pathway by blocking PKM2 activity has therapeutic potential for NKTL.

Significance of Serum Lactate Dehydrogenase in Childhood Acute Lymphoblastic Leukaemia

Introduction: Acute Lymphoblastic Leukaemia (ALL) is the most common childhood malignancy accounting for approximately 30% of childhood malignancies. The incidence rate of leukaemia in various parts of India varies from 0.3-1.2%. Lactate Dehydrogenase (LDH) is a pyridine-linked enzyme which is involved in metabolism of glucose in normal tissue. In leukaemic cells, there is loss of coordination of glycolytic sequence and tricarboxylic acid cycle, which leads to increased utilization of glucose. As there is high cell turnover, this leads to increased cell burden and high levels of serum LDH in ALL and the increase is much more than other haematological malignancies barring Burkitts lymphoma. Aim: To study the level of LDH in ALL cases at the time of diagnosis in comparison with Non ALL cases. Materials and Methods: Fifty five cases of ALL and 23 cases of Non ALL haematological malignancies as control were evaluated based on clinical manifestations, haematological parameters, peripheral blood picture and bone marrow findings. Serum LDH was estimated at the time of presentation by Cobas 6000, a photometrically automated system. Statistical analysis was done using SPSS version 20. Results: In our study, high serum LDH levels were seen in 89.1% (49) cases and normal levels in 10.9% (6) cases. High blast percentage i.e., >20% on peripheral smear (65.5%) was associated with high serum LDH level. On correlation of serum LDH with peripheral smear blast percentage, a p-value of <0.05 was obtained which shows a significant correlation Conclusion: Serum LDH level can be considered as a simple cost-effective tool in the presumptive evaluation of childhood Acute Lymphoblastic Leukaemia. LDH in combination with Uric acid helps in detecting tumourlysis syndrome at an early stage thereby aiding in early management.

2,3‐Diphosphoglyceric acid increase in carotenoid‐treated hypercholesterolemic rabbits (674.4)

2,3‐Diphosphoglyceri c Acid Increase in Carotenoid Treated Atherogenic Rabbits Jeffrey Jordan Andry Diminished oxygen diffusivity in blood may be induced by hypercholesterolemia in rabbits and is thought to play a major role in the increased arterial permeability that supports atherogenesis. Hypercholesterolemic rabbits treated with the carotenoid Crocetin (CR) (extracted from saffron) for at least 4 months, has been found to increase oxygen diffusivity, lower blood cholesterol (CHO) and reduce atherogenesis. This short term study focuses on the ability of Crocetin and B Carotene (BC) treatment of hypercholesterolemic rabbits to alter their blood levels of 2,3‐Diphosphoglyceric Acid (DPG) , a component of the glycolytic sequence which causes oxygen release from hemoglobin. Nine New Zealand Strain, male rabbits (1.4 Kg av wt ) were fed an Atherogenic Diet (AD) , ad libitum, of 92% Purina Rabbit Chow, 6% Corn Oil and 2% Cholesterol, for 5 weeks. The animals were divided into 3 equal groups and injected im. on alternate days as follows: I. Control (CO) Group ‐ 0.2 ml saline, II. CR Group ‐ 2mg. CR/ 0.2ml saline and III. BC Group‐ 2mg BC/0.2ml saline. DPG assays on whole blood samples after 3 weeks of treatment averaged an increase of 8.6% DPG in blood of CR treated rabbits vs CO values. After 5 weeks, of treatment, the average DPG level was 31.9% higher in the blood samples of CR treated rabbits, and for BC samples 2.6% higher compared to the CO DPG value. Average CHO assays of blood plasma gave substantially higher values in the carotenoid treated rabbits ( 36.1% for CR and 31.5% for BC assays) compared to the CO plasma values. The increase in 2,3 DPG in the blood of CR treated rabbits vs CO assays was significant after only 5 weeks of study despite substantial hypercholesterolemia found in that group. There was slightly lowered early atherogenesis found on examination of the aortae of the CR group vs CO aortae at autopsy.

METHYLGLYOXAL AND GLUCOSE METABOLISM: A HISTORICAL PERSPECTIVE AND FUTURE AVENUES FOR RESEARCH

Methylglyoxal, an alpha-oxoaldehyde discovered in the 1880s, has had a hectic scientific career, at times being considered of fundamental importance and at other times viewed as playing a very subordinate role. Much has been learned about methylglyoxal, but the function of its production in the metabolic machinery is still unknown. This paper gives an overview of the changing role of methylglyoxal from a historical aspect and arrives at the conclusion that methylglyoxal is tightly bound to glycolysis from an evolutionary perspective, its production therefore being inevitable. It is not situated in the main stream of the glycolytic sequence, but a role can be assigned to its production in the phosphate supply of operating glycolysis in some prokaryotes and yeast under conditions of phosphate deficiency. This function is presumed to be performed by the enzyme methylglyoxal synthase, which is specialized for the conversion of dihydroxyacetone-phosphate to methylglyoxal. However, it is still unknown whether this enzyme and this kind of regulation also exist in animals.

Glycolytic sequence and respiration of Debaryomyces hansenii as compared to Saccharomyces cerevisiae

The fermentation and respiration activities of Debaryomyces hansenii were compared with those of Saccharomyces cerevisiae grown to stationary phase with high respiratory activity. It was found that: (a) glucose consumption, fermentation and respiration were lower than for S. cerevisiae; (b) fasting produced a much smaller decrease of respiration; (c) glucose consumed and not transformed to ethanol was higher; (d) in S. cerevisiae, full oxygenation prevented ethanol production but this effect was reversed by CCCP, whereas D. hansenii still showed some ethanol production under aerobiosis, which was moderately increased by CCCP. ATP levels were similar in the two yeasts. Levels of glycolytic intermediaries after glucose addition, and enzyme activities, indicated that the main difference and limiting step to explain the lower fermentation of D. hansenii is phosphofructokinase activity. Respiration and fermentation, which are lower in D. hansenii, compete for the re-oxidation of reduced nicotinamide adenine nucleotides; this competition, in turn, seems to play a role in defining the fermentation rates of the two yeasts. The effect of CCCP on glucose consumption and ethanol production also indicates a role of ADP in both the Pasteur and Crabtree effects in S. cerevisiae but not in D. hansenii. D. hansenii shows an alternative oxidase, which in our experiments did not appear to be coupled to the production of ATP.

Enzymes of glycolysis are functionally associated with the mitochondrion in Arabidopsis cells.

Mitochondria fulfill a wide range of metabolic functions in addition to the synthesis of ATP and contain a diverse array of proteins to perform these functions. Here, we present the unexpected discovery of the presence of the enzymes of glycolysis in a mitochondrial fraction of Arabidopsis cells. Proteomic analyses of this mitochondrial fraction revealed the presence of 7 of the 10 enzymes that constitute the glycolytic pathway. Four of these enzymes (glyceraldehyde-3-P dehydrogenase, aldolase, phosphoglycerate mutase, and enolase) were also identified in an intermembrane space/outer mitochondrial membrane fraction. Enzyme activity assays confirmed that the entire glycolytic pathway was present in preparations of isolated Arabidopsis mitochondria, and the sensitivity of these activities to protease treatments indicated that the glycolytic enzymes are present on the outside of the mitochondrion. The association of glycolytic enzymes with mitochondria was confirmed in vivo by the expression of enolase- and aldolase-yellow fluorescent protein fusions in Arabidopsis protoplasts. The yellow fluorescent protein fluorescence signal showed that these two fusion proteins are present throughout the cytosol but are also concentrated in punctate regions that colocalized with the mitochondrion-specific probe Mitotracker Red. Furthermore, when supplied with appropriate cofactors, isolated, intact mitochondria were capable of the metabolism of (13)C-glucose to (13)C-labeled intermediates of the trichloroacetic acid cycle, suggesting that the complete glycolytic sequence is present and active in this subcellular fraction. On the basis of these data, we propose that the entire glycolytic pathway is associated with plant mitochondria by attachment to the cytosolic face of the outer mitochondrial membrane and that this microcompartmentation of glycolysis allows pyruvate to be provided directly to the mitochondrion, where it is used as a respiratory substrate.

Effects of augmented delivery of pyruvate on myocardial high-energy phosphate metabolism at high workstate.

This study was performed to determine whether the fall in myocardial high-energy phosphates (HEP) that occurs during high workstates can be ascribed to either inadequate glycolytic pyruvate generation and conversion to acyl-CoA or limitation of long-chain fatty acid transport into the mitochondria. This was tested by using infusions of either pyruvate or butyrate in anesthetized dogs. Pyruvate was used because it bypasses the glycolytic sequence of reactions, activates pyruvate dehydrogenase, and increases mitochondrial NADH concentration ([NADH(m)]) in isolated myocardium, whereas butyrate enters the mitochondria without need for transport by the rate-limiting, palmitoyl-carnitine transporter. Increasing blood pyruvate from 0.16 +/- 0.016 mM to >3 mM did not alter baseline HEP levels determined with (31)P nuclear magnetic resonance, but caused an increase in the rate-pressure product and a modest increase in myocardial oxygen consumption (MVO(2)). Infusion of dobutamine + dopamine (each 20 microg x kg(-1) x min(-1) iv) increased MVO(2) and caused decreases of myocardial phosphocreatine (PCr)/ATP. Pyruvate partially reversed the decrease of HEP levels produced by catecholamine stimulation, whereas butyrate had no effect. Neither pyruvate nor butyrate caused an increase of MVO(2) during catecholamine infusion. Deoxymyoglobin was not detected by (1)H magnetic resonance spectroscopyy in any group. The data demonstrate that carbon substrate availability to the mitochondria is not the only cause of the reduction of PCr/ATP that occurs at high workstates. Supplemental pyruvate (but not butyrate) attenuated the reduction of PCr/ATP during the high workstates; this may have resulted from direct effects on intermediary metabolism or from other effects such as the free radical scavenging activity of pyruvate.

The NADPH-dependent electron flow in chloroplasts of the higher plants

The NADPH-dependent reduction of some photosynthetic electron carriers in the dark, and the reduction of NADP+ associated with the glycolytic sequence and the oxidative pentose phosphate pathway in chloroplasts are reviewed. The postulated pathways of electron transports sensitive and insensitive to antimycin A are also evaluated. It is proposed that the electron flow, predominantly through cytochrome bf complex, may be also involved in the pathway of NADPH-dependent and antimycin A-insensitive back electron transport. An information on the chlororespiration in higher plants is also included.

Medium-chain fatty acids as short-term regulators of hepatic lipogenesis.

Short-term exposure of isolated rat hepatocytes to short- and medium-chain fatty acids led to an activation of acetyl-CoA carboxylase as measured in digitonin-permeabilized hepatocytes. Up to a certain concentration, typical for each of the fatty acids used, fatty acid-dependent activation of acetyl-CoA carboxylase coincided with an increase in the rate of fatty acid synthesis in intact hepatocytes, as determined by the incorporation of 3H from 3H2O water into fatty acids. At higher concentrations loss of stimulation of fatty acid synthesis occurred, but not the enhancement of carboxylase activity. With the fatty acids tested (C8:0-C14:0), the peak in fatty acid synthesis coincided with a peak in the level of malonyl-CoA. The onset of the stimulation of carboxylase activity coincided with the start of the peak in both fatty acid synthesis and malonyl-CoA. The longer the chain length of the fatty acid added, the lower the concentration at which the rate of fatty acid synthesis and the level of malonyl-CoA reached a peak and carboxylase activity started to become elevated. In cell suspensions incubated with increasing concentrations of fatty acids, accumulation of lactate decreased progressively. The latter observation, in combination with the fact that the activity of acetyl-CoA carboxylase is not always related to the rate of fatty acid biosynthesis, suggests that under these conditions not the activity of the carboxylase but the flux through the glycolytic sequence determines, at least in part, the rate of fatty acid synthesis de novo.

Developmental Expression of Neuron-Specific Enolase Immunoreactivity and Cytochrome Oxidase Activity in Neocortical Transplants

The present study has examined certain metabolic markers in fetal neocortical tissue transplanted to the cortex, hippocampus, striatum, or ventricle. Particularly, the immunocytochemical expression of neuron-specific enolase (NSE) was studied in a series of host rats ranging between 10 days and 15 months postoperative. NSE is a major glycolytic pathway enzyme found in all neurons. The antibody to NSE is a very reliable marker for neuronal functional metabolic activity and developmental status and its onset has been shown to coincide with synaptic connections. In some grafts oxidative metabolic status was investigated using cytochrome oxidase (CO) histochemistry. In addition, the normal development of NSE expression in rat neocortex was also examined. In normal development, NSE was weakly expressed in fetal brain, but by 1-2 weeks postnatal the enzyme was strongly expressed in all neurons. Typical cortical laminar patterns were evident at 30 days with neurons in layer V and scattered interneurons the most strongly stained. In cortex-cortex transplants NSE expression was very weak; at 1-3 weeks postoperative, it was practically nonexistent; and at all later times only a minority of neurons had normal expression when compared to that in normal development even though by Nissl staining standards in adjacent sections they appeared "normal." Labeling indices ranged between 30 and 49%. Intraventricular grafts had consistently low NSE expression with labeling indices ranging between 18 and 46%. However, when the neocortical tissue was placed in other regions, neuronal NSE appeared only slightly below normal. CO histochemistry corroborated the NSE activity with regards to graft placement. Several possibilities that may account for reduced NSE profile in transplanted neurons include incomplete migration patterns, reduced synaptic connectivity, and potential ischemia causing lowered protein synthesis during reestablishment of vascular connections. If neuronal glycolysis is weakened, it is possible that neurotransmitter production or axonal transport are reduced. Since most energy capacity in brain is dependent on the glycolytic sequence for oxidative metabolism, reduced glycolytic capacity, as depicted by NSE expression, may suggest the presence of transplanted neurons that have adapted to their new environment with a relatively immature profile.

Studies on glycolytic enzymes of plasmodium knowlesi, a simian malaria parasite, and infected host erythrocytes

Almost all of the important enzymes of glycolytic sequence were studied in isolated schizonts of Plasmodium knowlesi as well as in normal and P. knowlesi parasitized rhesus red blood cells. Significant activities of all the glycolytic enzymes assayed were observed in cell-free schizonts and the levels of all were found to be considerably elevated in infected host erythrocytes, confirming that the consumption of glucose is dramatically increased in host red cells, consequent to malaria infection.

Alterations in host regulatory glycolytic enzymes during pathogenesis of primate malaria and following chloroquine therapy

Hexokinase, phosphofructokinase and pyruvate kinase, the regulatory enzymes of the glycolytic sequence, showed progressive increases in their activities with the rise of parasitaemia in Plasmodium knowlesi-infected rhesus monkey serum and red blood cells. Chloroquine therapy cleared the parasitaemia in 72 h and brought the elevated levels of these enzymes back to almost normal in about 30 days.

Cellular differentiation and the microcompartmentation of glycolysis

In this paper, the main features of the cellular activities of the glycolytic enzymes during growth and tissue differentiation are summarized, and correlated with the occurrence of multiple forms of these enzymes, and with their degree of interaction with subcellular structure. The substantial evidence for micro-organization of the glycolytic sequence is described, as well as its significant contribution to the diverse physiological situations encountered during development. Based on this evidence, a modular, biphasic model of glycolytic activity has been developed, with associated features of microcompartmentation and segmentation. Evidence has been provided that these phenomena play important roles in meeting the special needs of emerging cell types during early ontogeny, as well as offering the potential for increased flexibility and control of glycolysis in specialized physiological situations in the adult organism.

Regulation of muscle carbohydrate metabolism during exercise 1

This review examines the mechanisms that regulate muscle carbohydrate metabolism during exercise. Muscle carbohydrate utilization is regulated primarily by two factors, namely, delivery of substrate to the glycolytic pathway either from glycogenolysis or from transport of extracellular glucose into the fibers, and formation of triosephosphate by phosphofructokinase. The regulation involves the integration of the glycolytic controls with other metabolic controls and the needs of the whole muscle in meeting the physiological demand. The controls operating in the glycolytic sequence in vivo appear to couple glycolytic recruitment to signals from the rate of energy demand, the TCA cycle state, and the mitochondrial redox state so as to satisfy the major regulatory goal of maintaining the supply of ATP for tension development.

Relation of phosphatidylinositol metabolism to glycolytic pathway in skeletal muscle membranes

Skeletal muscle triads are possessing the whole set of enzymes of the phosphatidylinositol (PI)-linked signal generating pathway, PI-kinase, PI(4)P-kinase, and PI(4,5)P2-phospholipase C (PLC). The activities of these enzymes are comparable to those found in other cell types for which a functional role of the PI-pathway in intracellular signal transduction has been established. For skeletal muscle an unequivocal function and an initiating signal for Ins(1,4,5)P3-liberation is still unknown. However, the observed Ca-dependency of PLC activity suggests that here Ins(1,4,5)P3 production is a consequence rather than a cause of increasing cytosolic Ca2+. Recently, the glycolytic enzyme aldolase, whose activity can be modulated by inositol polyphosphates, has been localized in the triadic structure. The enzyme which has a high affinity to Ins(1,4)P2, Ins(1,4,5)P3 and Ins(1,3,4,5)P4, seems to be compartmentalized to the junctional foot structure from which it is released upon binding of these molecules. This phenomenon could reflect a capability for regulation of the glycolytic flux even for aldolase, especially if a non steady-state situation in the junctional gap is considered. Meanwhile we have accumulated evidence for the operation of a partial glycolytic sequence in the junctional region established by the enzymes aldolase, glyceraldehyde-3-P (GAP) dehydrogenase and phosphoglycerate kinase. This system is able to produce ATP upon oxidation of GAP and could be, because of the inositol polyphosphate-sensing abilities of aldolase, a target for the membrane associated PI-pathway. The ATP production is however transient which indicates the coupling to an ATP hydrolyzing reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of 1,3‐bisphosphoglycerate transfer from phosphoglycerate kinase to glyceraldehyde‐3‐phosphate dehydrogenase

1. The kinetics of 1,3-bisphosphoglycerate binding to glyceraldehyde-3-phosphate dehydrogenase have been examined by stopped-flow techniques in the absence and presence of phosphoglycerate kinase, using enzyme concentrations in the range 0.5-40 microM. Rate and equilibrium constant estimates for the interaction of the ligand with the two enzymes are reported. 2. The kinetics of ligand transfer from the binary complex of bisphosphoglycerate and phosphoglycerate kinase to the binary complex of NAD+ and glyceraldehyde-3-phosphate dehydrogenase conform excellently to the predictions of a standard free-diffusion mechanism and exhibit no detectable contributions from a mechanism of direct (channelized) transfer of bisphosphoglycerate between the two enzymes. 3. Previously reported evidence that the binary complex of bisphosphoglycerate and phosphoglycerate kinase may act (in the presence of NADH) as a substrate for glyceraldehyde-3-phosphate dehydrogenase according to Michaelis-Menten kinetics is based on a misinterpretation of the experimental observations that can be attributed to neglect of the autocatalytic effect of NAD+ produced during the reaction. Experiments performed under conditions where the autocatalytic effect of NAD+ is eliminated provide clear evidence that the kinetics of utilization of the kinase-bisphosphoglycerate complex for enzymic NADH reduction are consistent with prior dissociation of the complex according to a free-diffusion mechanism of metabolite transfer and incompatible with a mechanism of direct metabolite transfer. 4. A kinetic argument is presented which renders implausible the very idea that direct metabolite transfer between 'soluble' consecutive enzymes in metabolic pathways may offer any catalytic advantages in comparison to metabolite transfer by free diffusion. A mechanism of direct metabolite transfer seems intuitively attractive only because one tends to disregard the diffusional processes required to bring the consecutive enzymes together and to separate them when the transfer has been completed. Direct metabolite transfer would be expected to be catalytically advantageous only in tightly bound multienzyme complexes showing no kinetically significant tendency to dissociate. 5. It is concluded that mechanisms of direct metabolite transfer have not been convincingly demonstrated to apply, nor are they likely to apply, between 'soluble' consecutive enzymes in metabolic pathways, at least not in the glycolytic sequence of reactions.

Circuit analysis of the oscillatory state in glycolysis

The oscillatory state of glycolysis in yeast extracts has been analysed by methods known from electronic circuit studies. The time course of the reactions are calculated by the method of least squares from experimentally determined sets of the concentrations of most of the metabolites. The dynamics of the glycolytic network of reactions can then be represented in terms of flow versus driving force (current versus voltage in the corresponding electronic circuit). The analysis of the dynamics leads to the conclusion that glycolysis is switched on and off in a pulsed manner during the oscillatory state. The resulting pulsed flow cannot only be measured with glycolytic end products, like carbon dioxide or ethanol, but can also readily be demonstrated by diagrams of reaction rates of single enzymic steps even in the initial stages of the glycolytic sequence. An analytic method widely applied to electronic circuits also proved to be useful in the study of the dynamics of a complex enzymic network.

Enzymes of carbohydrate metabolism ofCotugnia digonopora and their activity in the presence of anthelmintics,in vitro

Cotugnia digonopora, a fowl cycllophyllidean cestode, was found to possess most of the enzymes, associated with the glycolytic sequence and phosphoenolpyruvate branch point, in the cytosol fraction. Enzymes of malate metabolism were predominantly mitrochondrial. Anthelmintic agents inhibited hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, malate dehydrogenase, fumarate reductase, and malic enzyme. In intact worms this effect was significantly reduced. However, the activities of glycogen Phosphorylase and pyruvate kinase were significantly enhanced.

Glycolysis--new concepts in an old pathway.

A survey of the existing data on the interactions of glycolytic enzymes with the cellular structure in mammalian tissues has substantiated the occurrence of an extensive degree of such associations in all tissues and during all stages of development. Furthermore, a considerable specificity was evident between the individual multiple forms of the enzymes in relation to these associations. In reviewing these data, a model has been developed which proposes that the glycolytic sequence is best described as consisting of a number of segments in vivo, each segment formed by a cluster of isozymes, many of which can interact with the actin containing filaments of the cytomatrix. The novel features of this segmentation and compartmentation have been described, and evidence has been provided that these phenomena collectively play a key role in meeting the different types of energy requirement in the cytoplasm of divergent cell types, with the wide selection of isozymes in this system offering the potential for increased flexibility and control in this important area of metabolism.

Muscle energy metabolism in uremia

Energy-rich phosphagens were measured in 11 patients with end-stage chronic renal failure and 11 nonuremic subjects. A significant decrease of ATP, phosphocreatine, total adenine nucleotides, lactate, and energy charge was found. The present results can be referred both to glycolytic sequence disturbances and to the lack of substrates characteristic of uremia.