The mechanism of adduct formation between NAD+ and pyruvate bound to pig heart lactate dehydrogenase

Wilton, David C.

doi:10.1042/bj1770951

Cited by 10 publications

(4 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results indicate that the inhibitory effect of pyruvate is highly dependent on pH, and, as Cleland (1970) indicated, this effect can be considered to be uncompetitive. Results obtained recently by us (D. De Arriaga, J. Soler & E. Cadenas, unpublished work) are compatible with the proposal that an abortive ternary complex involving enzyme, NAD+ and pyruvate is responsible for this inhibition, in the same manner as proposed by several authors (Sugrobova et al, 1975;Wilton, 1979;Trommer et al, 1979;). Moreover, we found that the inhibitory effect of pyruvate depends also on the temperature, a fact that has been reported for lactate dehydrogenase from several sources (Somero, 1973;Eichner & Kaplan, 1977;Kao & Farley, 1978), and also on NADH concentration in such a way that inhibition of lactate dehydrogenase should increase with an increased concentration of NADH.…”

Section: Discussionsupporting

confidence: 90%

Influence of pH on the allosteric properties of lactate dehydrogenase activity of Phycomyces blakesleeanus

Arriaga¹,

Soler²,

Cadenas³

1982

Biochemical Journal

View full text Add to dashboard Cite

1. Lactate dehydrogenase from mycelium of Phycomyces blakesleeanus showed positive homotropic interactions with NADH at all pH values studied (pH 5.0-7.7). The calculated values for the first and last intrinsic association constants remained unaltered with pH, in contrast with the Hill coefficient value, which varied significantly, reaching its maximum values at pH 6.0 and 7.7. This suggests the hypothesis that pH regulates these homotropic effects by changes in the value of the intermediate intrinsic association constants. 2. From pH 7.2 to 7.7 lactate dehydrogenase exhibited, likewise, positive homotropic interactions with pyruvate. There were practically no changes in the first and last intrinsic association constants and in Hill coefficient values with pH. At pH values below 7.2 (pH 5.0-6.8) the enzyme showed high substrate inhibition, which was highly dependent on pH, NADH concentration and temperature. By way of substrate inhibition pH regulates, primarily, lactate dehydrogenase activity towards pyruvate, since the homotropic effects appear not to be dependent on pH. 3. Fructose 1,6-bisphosphate is a true allosteric effector of lactate dehydrogenase of Phycomyces blakesleeanus. it decreases positive co-operativity with NADH, and on the other hand pyruvate co-operativity turns into mixed co-operativity. In addition, the effector decreases the inhibitory effect caused by pyruvate.

show abstract

Section: Discussionsupporting

confidence: 90%

Influence of pH on the allosteric properties of lactate dehydrogenase activity of Phycomyces blakesleeanus

Arriaga¹,

Soler²,

Cadenas³

1982

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…NAD(P) is also sensitive to addition of nucleophiles at C-4 of the pyridinium ring (OzoIs and Marinetti, 1969;Everse eral., 197th;Smith, 1976, 1977;Biellman et al, 1979). Several dehydrogenase enzymes catalyse the destructive addition of nucleophiles to NAD (Everse et al, 1971b;Arnold and Kaplan, 1974;Parker, Lodola and Holbrook, 1978;Wilton, 1979;Burgner and Ray, 1984).…”

Section: Preparation Of the Nicotinamide Cofactorsmentioning

confidence: 97%

Cofactor Regeneration for Enzyme-Catalysed Synthesis

Chenault

Simon

Whitesides

1988

Biotechnology and Genetic Engineering Reviews

198

126

View full text Add to dashboard Cite

“…In aqueous solution, the keto–enol equilibrium for pyruvate favours the keto form to a very large extent [70–72]. The rate of enolization, however, is substantial, especially in the presence of a divalent cation, such as ionized calcium or magnesium [73, 74]. Thus, it is conceivable that some of the pharmacological effects of EP are actually mediated by the enol tautomer.…”

Section: Introductionmentioning

confidence: 99%

Ethyl pyruvate: a novel anti‐inflammatory agent

Fink

2007

Journal of Internal Medicine

150

115

View full text Add to dashboard Cite

Abstract. Fink MP (University of Pittsburgh Medical School, Pittsburgh, PA, USA). Ethyl pyruvate: a novel anti-inflammatory agent (Review). J Intern Med 2007; 261: 349-362.Ethyl pyruvate (EP) is a simple derivative of the endogenous metabolite, pyruvic acid. Treatment with EP has been shown to improve survival and/or ameliorate organ dysfunction in a wide variety of preclinical models of critical illnesses, such as severe sepsis, acute respiratory distress syndrome, acute pancreatitis and stroke. EP was originally regarded as simply a way to administer pyruvate anion, whilst avoiding some of the problems associated with the instability of pyruvate in aqueous solutions. Increasingly, however, it is becoming apparent that certain pyruvate esters, including EP, have pharmacological effects, such as suppression of inflammation, that are quite distinct from those exerted by pyruvate anion. EP has been tested in human volunteers and shown to be safe at clinically relevant doses. It remains to be determined whether EP can be used successfully to treat human diseases.

show abstract

The mechanism of adduct formation between NAD+ and pyruvate bound to pig heart lactate dehydrogenase

Cited by 10 publications

References 20 publications

Influence of pH on the allosteric properties of lactate dehydrogenase activity of Phycomyces blakesleeanus

Influence of pH on the allosteric properties of lactate dehydrogenase activity of Phycomyces blakesleeanus

Cofactor Regeneration for Enzyme-Catalysed Synthesis

Ethyl pyruvate: a novel anti‐inflammatory agent

Contact Info

Product

Resources

About