Showing papers on "Pyruvate dehydrogenase kinase published in 1972"
462 citations
TL;DR: Evidence is presented that the bovine kidney and heart dihydrolipoyl transacetylases are very similar and that each enzyme does indeed consist of 60 apparently identical polypeptide chains.
264 citations
TL;DR: Preliminary data indicate that the molar concentration of the kinase and the phosphatase is about an order of magnitude less than that of their protein substrate, pyruvate dehydrogenase.
249 citations
TL;DR: Dihydrolipoyl transacetylase markedly stimulates the rate of phosphorylation of PDH by PDH kinase and is found to lower the apparent Km of the kinase for PDH from about 20 μ m to about 0.6 μ m.
223 citations
TL;DR: It is concluded that in liver, similar to heart muscle and kidney, fatty acids play an important role in the control of pyruvate dehydrogenase interconversion.
Abstract: Active form and total activity of pyruvate dehydrogenase were measured in rat liver homogenates The activity obtained immediately after homogenization was considered to represent the active form, ie dephospho pyruvate dehydrogenase, originally present in the liver Enzyme activity found after incubation of the homogenate with Mg2+ and partially purified pyruvate dehydrogenase phosphatase from pig heart, whereby inactive dehydrogenase is dephosphorylated to give the active form, was regarded as total pyruvate dehydrogenase activity In the livers from normal fed rats, the active form accounts for only one sixth of total pyruvate dehydrogenase activity This differs from other tissues such as heart muscle, kidney, brain and adipose tissue where about two thirds of total pyruvate dehydrogenase are present as the active form (Wieland et al, 1971; Siess et al, 1971)
To elucidate the possible role of pyruvate dehydrogenase interconversion in the regulation of pyruvate metabolism in liver, the activity of active and total pyruvate dehydrogenase were determined in livers of rats subjected to various metabolic conditions After fasting and refeeding with glucose as well as after treatment with nicotinic acid or insulin there were significant changes of active dehydrogenase activity without gross alterations of total activity In general, metabolic states associated with decreased plasma fatty acids resulted in an increase of active pyruvate dehydrogenase whereas a rise in plasma fatty acids led to a lowering It is concluded that in liver, similar to heart muscle and kidney (Wieland et al, 1971), fatty acids play an important role in the control of pyruvate dehydrogenase interconversion The significance of this mechanism for the regulation of pyruvate metabolism in liver relative to the feedback control of pyruvate dehydrogenase by acetyl-CoA is discussed
181 citations
151 citations
TL;DR: Pyruvate carboxylase may be present in insect flight muscle for the provision of oxaloacetate to support the large increase in activity of the tricarboxylic acid cycle which occurs when an insect takes flight.
Abstract: 1. The activities of pyruvate carboxylase, phosphoenolpyruvate carboxylase and fructose diphosphatase in crude homogenates of vertebrate and invertebrate muscles are reported. 2. Pyruvate carboxylase activity was present in all insect flight muscles that were investigated: in homogenates of bumble-bee flight muscle the activity was inhibited by ADP and activated by acetyl-CoA, and it was distributed mainly in the mitochondrial fraction. This is the first demonstration of pyruvate carboxylase activity in muscle. However, the activity appears to be restricted to insect flight muscle, since it was not found in other invertebrate or vertebrate muscles. 3. Since the three enzymes were never found together in the same muscle, it is concluded that these enzymes cannot provide a pathway for the synthesis of glycogen from lactate or pyruvate in muscle. Other roles for these enzymes in muscle are suggested. In particular, pyruvate carboxylase may be present in insect flight muscle for the provision of oxaloacetate to support the large increase in activity of the tricarboxylic acid cycle which occurs when an insect takes flight.
143 citations
TL;DR: Evidence is presented that the activity of the PDH phosphatase from bovine kidney and heart is increased about tenfold when it is attached to the transacetylase, which could provide an important mechanism for regulation of the phosphorylation-dephosphorylation cycle.
143 citations
TL;DR: Results suggested that there may be two types of pyruvate binding sites on the LDH from S. mutans, which appeared to be at least two binding sites for the activator which interacted in a cooperative manner.
Abstract: The lactate dehydrogenase (LDH) from Streptococcus mutans NCTC 10449 is under stringent metabolic control. The partially purified enzyme was specifically activated by high concentrations of fructose-1,6-diphosphate (FDP) and was inhibited by adenosine triphosphate. There appeared to be at least two binding sites for the activator which interacted in a cooperative manner. The interaction between the FDP sites was independent of the pH of the assay system, although the relative affinity of the enzyme for the activator was influenced by pH. There also appeared to be at least two pyruvate binding sites on the S. mutans LDH with some cooperative interaction between them, and the interaction between these sites was also independent of the hydrogen ion concentration. Two pyruvate analogues had different effects on the interaction of pyruvate with the LDH. One of the analogues, α-ketobutyrate, stimulated enzyme activity at limiting pyruvate concentrations, but had no significant effect at saturating concentrations of the substrate. The net effect of α-ketobutyrate was to shift the pyruvate saturation curve from sigmoidal to hyperbolic and to decrease the Hill coefficient from about 2.0 to 1.0. The other pyruvate analogue, oxamate, inhibited enzyme activity at all pyruvate concentrations but had no effect on the sigmoidal nature of the pyruvate saturation curve or on the apparent kinetic order of the reaction with respect to substrate. These results suggested that there may be two types of pyruvate binding sites on the LDH from S. mutans. Other kinetic properties of the S. mutans NCTC 10449 enzyme were studied and compared with those exhibited by the LDH from several other strains of the organism.
114 citations
TL;DR: The pattern of enzymes related to the synthesis of C1 units by several clostridia demonstrates that either a pyruvate-formate-lyase or a CO2-reductase reaction leads to the formation of formate, which is required for the synthesis in these bacteria.
Abstract: Pyruvate formate-lyase has been demonstrated in Clostridium kluyveri, C. butylicum and C. butyricum. The properties of the clostridial enzyme have been studied in more detail in cell-free lysates of C. butyricum. The following activities were investigated: pyruvate cleavage to acetylBiochemisches Institut der Universitat BRD-7800 Freiburg i. Br., Hermann Herder-Strase 7 German Federal RepublicBiochemisches Institut der Universitat BRD-7800 Freiburg i. Br., Hermann Herder-Strase 7 German Federal RepublicCoA and formate, pyruvate synthesis from acetyl-CoA and formate, and formate exchange with the carboxyl group of pyruvate.
Formate formation from pyruvate (substrate concentration for half-maximal velocity, ([S]0.5v= 1.6 mM) was dependent on coenzyme A ([S]0.5v= 0.012 mM). Pyruvate (100%) could be replaced to some degree by 2-oxobutyrate (31%), coenzyme A (100%) by dephosphocoenzyme A (40%).
In contrast to all other known pyruvate formate-lyase reactions the clostridial reaction was readily reversible. Pyruvate synthesis from acetyl CoA ([S]0.5v= 0.19 mM) and formate ([S]0.5v= 10 mM) proceeded with 40% of the velocity of the forward reaction.
The exchange reaction between pyruvate ([S]0.5v= 0.6 mM) and formate ([S]0.5v= 20 mM) was independent of CoA or phosphate. This activity was even inhibited in the presence of CoA.
DEAE-cellulose-treated extracts did not catalyze formate formation from pyruvate. The activity could however be restored by reduced ferredoxin, Co2+· thiol or Fe2+· dithiol complexes. When the lysates were treated with Dowex-potassium or charcoal in addition to DEAE-cellulose, reactivation required both one of the electron donors and S-adenosylmethionine. Methionine, ATP, ADP, AMP, methionine plus ATP, or S-adenosylhomocysteine could not substitute for S-adenosylmethionine. Rather, S-adenosylhomocysteine antagonized the reactivation dependent on S-adenosylmethionine. A similar inactivation-activation behavior was observed for the pyruvate formation and the exchange activities.
The pattern of enzymes related to the synthesis of C1 units by several clostridia demonstrates that either a pyruvate-formate-lyase or a CO2-reductase reaction leads to the formation of formate, which is required for the synthesis of C1 units in these bacteria.
111 citations
TL;DR: The results obtained suggest that gluconeogenesis is confined to the parenchymal cells of rat liver, suggesting that Kupffer cells only (probably) contain the M-type pyruvate kinase.
TL;DR: It appears that the thiamine-PP binding site and the phosphorylation site on PDH influence each other and that HETPP is bound to PDH in a different orientation or possibly at a different site than is thiamin-PP.
TL;DR: Both fatty acids reversed the inhibition of pyruvate carboxylase by ADP via changes in the intramitochondrial ATP:ADP ratio but they did this by differing mechanisms.
Abstract: Fluxes of pyruvate through the pyruvate dehydrogenase and the pyruvate carboxylase reactions in intact rat liver mitochondria were measured under various experimental conditions. When amounts of pyruvate not limiting for pyruvate dehydrogenase were present in the incubation medium, pyruvate carboxylase was found to be regulated essentially by the ATP:ADP ratio within the mitochondrial matrix. No direct correlation between pyruvate carboxylase activity and the level of intramitochondrial acetyl-CoA could be observed under these conditions.
When the ATP:ADP ratio within the matrix was decreased by elevation of the ADP concentration in the medium, a strong inhibition of the pyruvate carboxylase was observed. After addition of oleate to the medium this low ATP:ADP ratio within the matrix was increased and the inhibition of pyruvate carboxylase was partially reversed. It is demonstrated that this effect of oleate is probably caused by an inhibition of the adenine nucleotide translocase.
The effects of oleate on pyruvate carboxylase were compared to those of octanoate. In contrast to oleate, octanoate diminished the pool size of the exchangeable adenine nucleotides, ATP and ADP, within the matrix and oxidative phosphorylation was stimulated. The reduced level of intramitochondrial ADP and the increased rate of oxidative phosphorylation elevated the ATP:ADP ratio within the matrix and partially reversed the inhibition of the pyruvate carboxylase by ADP. Thus, both fatty acids reversed the inhibition of pyruvate carboxylase by ADP via changes in the intramitochondrial ATP:ADP ratio but they did this by differing mechanisms.
Octanoate was found to be much more rapidly activated and oxidized within the matrix than oleate. Furthermore, octanoate strongly inhibited pyruvate oxidation whereas with oleate this effect was much smaller.
The physiological implications of these findings are discussed in relation to the stimulation of gluconeogenesis by fatty acids in the liver.
TL;DR: It is concluded that the activation of pyruvate dehydrogenase by insulin is not due to the antilipolytic effect of the hormone and that the action of insulin in lowering adipose-cell concentrations of cyclic AMP does not afford an obvious explanation for the effect ofthe hormone.
Abstract: 1. Isolated rat epididymal fat-cell mitochondria showed an inverse relationship between ATP content and pyruvate dehydrogenase activity consistent with competitive inhibition of pyruvate dehydrogenase kinase by ADP. At constant ATP concentration pyruvate rapidly activated pyruvate dehydrogenase in fat-cell mitochondria, an observation consistent with inhibition of fat-cell pyruvate dehydrogenase kinase by pyruvate. Pyruvate dehydrogenase in fat-cell mitochondria was also activated by nicotinate (100mum) and by extramitochondrial Na(+) (replacing K(+)) but not by ouabain or insulin. 2. In rat epididymal fat-pads incubated in vitro pyruvate dehydrogenase was activated by addition of insulin in the absence of substrate or in the presence of glucose (10mm) or fructose (10mm). Glucose and fructose activated the dehydrogenase in the absence or in the presence of insulin, and pyruvate also activated in the absence of insulin. It is concluded that extracellular glucose, fructose and pyruvate may activate the dehydrogenase by raising intracellular pyruvate and that insulin may activate the dehydrogenase by some other mechanism. 3. Ouabain (300mum) and medium in which K(+) was replaced by Na(+), activated pyruvate dehydrogenase in epididymal fat-pads. Prostaglandin E(1) (1mug/ml), 5-methylpyrazole-3-carboxylate (10mum) and nicotinate (10mum), which are as effective as insulin as inhibitors of lipolysis and which like insulin lower tissue concentration of cyclic AMP (adenosine 3':5'-cyclic monophosphate), did not activate pyruvate dehydrogenase. Higher concentrations of prostaglandin E(1) (10mug/ml) and nicotinate (100mum) produced some activation of the dehydrogenase. 4. It is concluded that the activation of pyruvate dehydrogenase by insulin is not due to the antilipolytic effect of the hormone and that the action of insulin in lowering adipose-cell concentrations of cyclic AMP does not afford an obvious explanation for the effect of the hormone on pyruvate dehydrogenase. The possibility that the effects of insulin, ouabain and K(+)-free medium may be mediated by Ca(2+) is discussed.
TL;DR: These studies lend support to the view that, in liver, the state of the pyruvate dehydrogenase system is under metabolic control and that ADP may thereby play an essential role.
Abstract: Active (dephospho) and inactive (phospho) forms of pyruvate dehydrogenase are extracted from freshly prepared rat liver mitochondria in the same proportion as from freeze-clamped samples of whole rat liver. The active form increases within a few minutes on incubation of mitochondria with pyruvate (state 4) in a concentration-dependent manner, the maximal effect (80% active form) being obtained at 2 mM pyruvate. Half-maximal activation occurs between 0.3 and 0.4 mM pyruvate. ADP, in the absence of exogenous substrate, also stimulates the formation of active pyruvate dehydrogenase. Palmitoyl-l(–)-carnitine counteracts the effects of pyruvate or ADP on pyruvate dehydrogenase interconversion. The lowest values of the active form of the enzyme were observed during state 4 respiration with palmitoyl-l(–)-carnitine, succinate, 2-oxoglutarate, and 3-hydroxybutyrate. These studies lend support to the view that, in liver, the state of the pyruvate dehydrogenase system is under metabolic control and that ADP may thereby play an essential role.
TL;DR: The role of fatty acids in the regulation of kidney cortex pyruvate metabolism is confirmed and the results are compared with previously published observations on theregulation of pyruVate dehydrogenase in vivo and confirmed.
Abstract: Pyruvate dehydrogenase activity was measured in extracts of isolated kidney cortex tubules, prepared by collagenase treatment. The measured activities were comparable to those described previously for whole kidney homogenates.
Incubation of tubules in vitro in the absence of exogenous substrates led to a steady increase in enzyme activity over 30 min. This increase was not significantly changed by the addition of several gluconeogenic substrates including lactate, glutamine, glutamate, glycerol, fructose and malate. 1 mM oleate, 5 mM acetate and 20 mM 2-oxoglutarate however, prevented this increase completely. In contrast, glucose and dihydroxyacetone accelerated the activation of pyruvate dehydrogenase during incubation in vitro. 20 mM pyruvate very rapidly activated pyruvate dehydrogenase with a following decrease below the activity of control experiments without substrate. 1 mM oleate and 20 mM 2-oxoglutarate counteracted the increase in pyruvate dehydrogenase activity caused by glucose and dihydroxyacetone and had no effect in the presence of 20 mM pyruvate.
Determination of the inactive part of pyruvate dehydrogenase after addition of purified pyruvate dehydrogenase phosphatase revealed that all changes observed were probably caused by enzymatic interconversion of pyruvate dehydrogenase.
The results are compared with previously published observations on the regulation of pyruvate dehydrogenase in vivo and confirm the role of fatty acids in the regulation of kidney cortex pyruvate metabolism.
TL;DR: The enzyme lactate dehydrogenase (LDH) exists as a complex system in vertebrate organisms and is encoded in two major structural genes, each resulting in a different subunit of LDH, resulting in the synthesis of more than fifteen isozymes in homozygous individuals.
TL;DR: Pyruvate carboxylases isolated from the livers of rats, chickens, and sheep were shown to catalyze the fixation of H14CO3- in the absence of acetyl-CoA and to be dependent upon the enzyme concentration in the assay solution.
TL;DR: It is concluded that pyruvate oxidation is probably limited by the respiratory chain in state 4 and by the NAD-linked isocitrate dehydrogenase in state 3, and the oxidation of 2-oxoglutarate by swollen mitochondria is also stimulated by high concentrations of ADP and phosphate, and is not uncoupled by arsenate.
Abstract: 1. High rates of state 3 pyruvate oxidation are dependent on high concentrations of inorganic phosphate and a predominance of ADP in the intramitochondrial pool of adenine nucleotides. The latter requirement is most marked at alkaline pH values, where ATP is profoundly inhibitory. 2. Addition of CaCl2 during state 4, state 3 (Chance & Williams, 1955) or uncoupled pyruvate oxidation causes a marked inhibition in the rate of oxygen uptake when low concentrations of mitochondria are employed, but may lead to an enhancement of state 4 oxygen uptake when very high concentrations of mitochondria are used. 3. These properties are consistent with the kinetics of the NAD-linked isocitrate dehydrogenase (EC 1.1.1.41) from this tissue, which is activated by isocitrate, citrate, ADP, phosphate and H+ ions, and inhibited by ATP, NADH and Ca2+. 4. Studies of the redox state of NAD and cytochrome c show that addition of ADP during pyruvate oxidation causes a slight reduction, whereas addition during glycerol phosphate oxidation causes a `classical' oxidation. Nevertheless, it is concluded that pyruvate oxidation is probably limited by the respiratory chain in state 4 and by the NAD-linked isocitrate dehydrogenase in state 3. 5. The oxidation of 2-oxoglutarate by swollen mitochondria is also stimulated by high concentrations of ADP and phosphate, and is not uncoupled by arsenate.
TL;DR: Comparison of enzyme activity ratios in vivo and in vitro suggest a shift between different metabolic pathways and the concentration of soluble protein increased significantly after the eels had been treated with PCP.
Abstract: 1. 1. The effects of PCP in vivo and in vitro on the activity profiles of hexokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, pyruvate kinase, lactate dehydrogenase, fumarase and cytochrome oxidase in the liver of the eel were investigated. 2. 2. In vivo the activities of pyruvate kinase and lactate dehydrogenase decreased after acute PCP poisoning. On the other hand, the activities of hexokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, fumarase and cytochrome oxidase showed increased activity. 3. 3. After a recovery period of 30 days in uncontaminated water the PCP-treated eels showed higher activity levels for all the investigated enzymes compared to the controls. 4. 4. Comparison of enzyme activity ratios in vivo suggest a shift between different metabolic pathways. 5. 5. In vitro PCP inhibits all the investigated enzymes. 6. 6. The concentration of soluble protein increased significantly after the eels had been treated with PCP.
TL;DR: From the experiments with the digitonin method it is concluded that the majority of the shared mitochondrial enzymes has a similar localization both in beef heart and rat liver mitochondria.
Abstract: Treatment of heavy beef heart mitochondria with different concentrations of digitonin, followed by centrifugation of the treated suspension resulted in a release of mitochondrial enzymes in a certain order. Monoamine oxidase and rotenone-insensitive NADH cytochrome c reductase were found primarily in the outer membrane fraction. At low concentrations of digitonin adenylate kinase and creatine kinase were in part released pointing to an intracristal localization; the remainder of these enzymes was found to be associated with the inner membrane-matrix fraction. The soluble citric cycle enzymes were found in the inner membrane-matrix preparation. They were released from the matrix in two groups: (a) isocitrate dehydrogenase, malate dehydrogenase, fumarase and aconitase and (b) 2-oxoglutarate dehydrogenase, pyruvate dehydrogenase and lipoate dehydrogenase. Enzymes intrinsic to the inner membrane were released at concentrations of digitonin higher than 0.4 mg/mg protein (cytochrome oxidase, succinate dehydrogenase, ATPase and 3-hydroxybutyrate dehydrogenase). The absence of citric cycle enzyme activity, except succinate dehydrogenase in submitochondrial particles prepared by sonication, also points to a localization of these enzymes in the matrix.
From the experiments with the digitonin method it is concluded that the majority of the shared mitochondrial enzymes has a similar localization both in beef heart and rat liver mitochondria.
Detergents such as digitonin, Lubrol WX and Titron X-100 induce the “twisted” configuration of the inner membrane of beef heart mitochondria, suspended in a sucrose medium, as visualized electron microscopically.
TL;DR: The data are consistent with the interpretation that TPP-dependent inactivation involves the action of bromopyruvate as an irreversible inhibitor which is directed into the complex by specific, but not necessarily irreversible, interaction with the pyruVate dehydrogenase component and ultimately blocks some site within the complex which is essential for catalytic activity in the over-all reaction.
TL;DR: This chapter discusses the properties and structure of pyruvate carboxylase, and the detection of stoichiometric concentrations of this coenzyme in purified preparations of the enzymes from the avian liver, the mammalian liver, Saccharomyces cerevisiae, and Pseudomonas citronellolis.
Abstract: Publisher Summary This chapter discusses the properties and structure of pyruvate carboxylase. Pyruvate carboxylase activity has been detected in most mammalian tissues examined, although high maximal catalytic capacities for this enzyme are confined to the liver, kidney cortex, and adipose tissue. The enzyme is also present in the avian and the amphibian liver, in yeasts, and in other fungi and bacteria. All pyruvate carboxylases detected, thus, far in vertebrate tissues require the presence of an acyl-CoA, such as acetyl-CoA, to catalyze a significant rate of pyruvate carboxylation. The microbial pyruvate carboxylases exhibit a wide diversity in their requirement for activation by this cofactor. In the case of detecting the presence of bound biotin, all pyruvate carboxylases examined are rapidly inactivated by incubation in the presence of avidin, a protein which has a high affinity for biotin. This inactivation is irreversible under most conditions and is prevented by the preincubation of the avidin preparation with excess biotin. The identification of pyruvate carboxylases as biotin-proteins is confirmed by the detection of stoichiometric concentrations of this coenzyme in purified preparations of the enzymes from the avian liver, the mammalian liver, Saccharomyces cerevisiae , and Pseudomonas citronellolis .
TL;DR: Pyruvate kinase (ATP:pyruvates phosphotransferase, EC 2.7.40) in muscle tissue of the sea mussel Mytilus edulis possesses properties which are similar to allosteric L-type pyruvATE kinase of the rat liver with respect to stimulation by phosphoenolpyruVate and Fru-1,6-P2.
TL;DR: The influence of Glc-1,6-P2 on hepatic and red blood cell pyruvate kinase (ATP: pyruVate phosphotransferase, EC 2.7.40) is quite similar to that of Fru-1-6- P2; the hexose diphosphates can replace each other in stimulating pyruve kinase; after maximal stimulation by one of the compounds, the other is not capable of further stimulation.
TL;DR: The possible role of mitochondria in modifying pyruvate kinase and other ion-sensitive cytoplasmic enzyme activities is discussed.
Abstract: 1. The modification of pyruvate kinase activity in vitro was examined by altering the environmental [Mg2+]/[Ca2+] ratio with EDTA on the one hand and isolated rat liver mitochondria on the other. 2. Controlled additions of Ca2+ and EDTA caused pyruvate kinase activity to be alternately and rapidly switched on and off. 3. By being able to accumulate Ca2+ in preference to Mg2+ rat liver mitochondria were able to alter the [Mg2+]/[Ca2+] ratio in the vicinity of pyruvate kinase and thereby modify the activity of this enzyme. 4. The possible role of mitochondria in modifying pyruvate kinase and other ion-sensitive cytoplasmic enzyme activities is discussed.
TL;DR: Cells from an adult liver when taken into culture resemble fetal liver rather than adult liver, and attempts to induce in these cells the isozymes of ATP-hexose phosphotransferase and pyruvate kinase characteristic of the adult liver have been unsuccessful.
Abstract: Isozyme patterns of the enzymes of ATP-hexose phosphotransferase, aldolase, and pyruvate kinase have been examined in a culture of cells derived from an adult rat liver. Normal adult liver characteristically contains glucokinase, aldolase B, and pyruvate kinase I isozymes. In contrast to this, the isozymes present in the cell line were found to be hexokinase, aldolase A, and pyruvate kinase III. Thus cells from an adult liver when taken into culture resemble fetal liver rather than adult liver. Attempts to induce in these cells the isozymes of ATP-hexose phosphotransferase and pyruvate kinase characteristic of the adult liver have been unsuccessful. The culture conditions were found to affect the nature of the kinetic properties of the pyruvate kinase isozyme in these cells. Cells maintained in the absence of glucose gave a sigmoidal-shaped substrate velocity curve for phosphoenolpyruvate, with aK
m of 0.33mm. However, when the enzyme was extracted from cells grown in the presence of glucose, a hyperbolic-shaped substrate velocity curve was found, with aK
m of 0.05mm. The two forms of this isozyme have been designated A and B, respectively. Form A can be converted to form B by preincubation with fructose diphosphate, whereas the B to A transition is mediated by ethylenediaminetetraacetate, ATP, or citrate. These two forms of the enzyme have distinctive properties in relation to inhibition by ATP, alanine, and phenylalanine, and to activation by fructose diphosphate. Their properties appear to resemble those of adipose tissue pyruvate kinase. The physiological significance of these properties is discussed.