Though the structures presented in crystallographic models of macromolecules appear to possess rock-like solidity, real proteins and nucleic acids are not particularly rigid. Most structural work to date has centred upon the native state of macromolecules, the most probable macromolecular form. But the native state of a molecule is merely its most abundant form, certainly not its only form. Thermodynamics requires that all other possible structural forms, however improbable, must also exist, albeit with representation corresponding to the factor exp( — Gi/RT) for each state of free energy Gi (see Moelwyn-Hughes, 1961), and one appreciates that each molecule within a population of molecules will in time explore the vast ensemble of possible structural states.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0033583500005217

Hydrogen exchange and structural dynamics of proteins and nucleic acids

Publisher Summary This chapter describes the advances with an emphasis on the structures of the alcohol dehydrogenases and the relationship between structure and function Yeast and mammalian alcohol dehydrogenase differ in substrate specificity and rate of catalytic activity The classic yeast enzyme is more specific for acetaldehyde and ethanol, which is consistent with its recognized physiological Significance to participate in alcohol fermentation at the end of the glycolytic pathway Enzyme forms with other functions and properties also occur in yeast The mammalian enzymes have broad substrate specificity and, even with primary alcohols, the maximum activity is not observed with ethanol Alcohols including ethanol, produced in the intestinal tracts mainly by bacterial actions, are found in the portal vein One physiological function of liver alcohol dehydrogenase may be to metabolize these products Structural studies have established that mammalian alcohol dehydrogenases have a distant evolutionary link to both the yeast and bacterial enzymes Ingested alcohol is metabolized to acetaldehyde mainly by the action of liver alcohol dehydrogenase

3 Alcohol Dehydrogenases

Publisher Summary Glutamate dehydrogenases, as a class, catalyze the reversible oxidative deamination of L-glutamate to α -ketoglutarate and ammonia The description of the characteristics of this reaction from a variety of sources show that, although all classed as glutamate dehydrogenase, the enzymes are different in terms of kinetic characteristics, metabolic function, and molecular properties The animal enzymes are sensitive to the concentration of purine nucleotides, can catalyze the reaction using either Nicotinamide adenine dinucleotide (NAD) or Nicotinamide adenine dinucleotide phosphate (NADP), and undergo a reversible polymerization reaction, which might influence the allosteric characteristics of the enzyme The non-animal sources are specific either for NAD or for NADP, are in general not influenced by purine nucleotides, and do not appear to undergo a reversible polymerization reaction These differences are related to the metabolic role of the reaction, which in animal tissues serves as an important link between carbohydrate and protein metabolism utilizing either α-ketoglutarate or glutamate depending on the condition of the cell, but which in non-animal organisms might act unidirectionally

L-Glutamate Dehydrogenases*

Glutamate dehydrogenase. v. the relation of enzyme structure to the catalytic function

Studies on the mechanism of fatty acid synthesis. XII. Acetyl coenzyme A carboxylase.

The Mechanism of Glutamate Dehydrogenase Reaction: III. THE BINDING OF LIGANDS AT MULTIPLE SUBSITES AND RESULTING KINETIC EFFECTS

L-GLUTAMIC dehydrogenase (GDH) has been shown to dissociate into sub-units under a variety of experimental conditions, such as dilution1, high or low pH2,3, and presence of DPNH4, urea5, diethylstilbœstrol6, or bicarbonate ions7. The relationship between the state of aggregation of the enzyme and its catalytic activity has been the subject of some controversy. Several investigators have attempted to relate the state of aggregation of the enzyme, as studied at high protein concentrations, to catalytic activity measured at protein concentrations several orders lower in magnitude6,8,9. Recent light scatter studies in this laboratory have shown that if the degree of splitting of the enzyme is plotted against pH and enzyme concentration, a quite irregular mathematical surface results2. Consideration of such surfaces plotted from experimental results obtained in the presence of various substrates, coenzymes, and other compounds suggested to us that it is, in general, quite invalid to relate catalytic activity measured under one set of conditions to degree of aggregation of the protein measured under different conditions. We therefore sought to measure both catalytic activity and the degree of aggregation of the protein in identical solutions so that these two properties might be related to each other in a valid manner.

Dallas G. Cross

Papers

The Mechanism of Glutamate Dehydrogenase Reaction: III. THE BINDING OF LIGANDS AT MULTIPLE SUBSITES AND RESULTING KINETIC EFFECTS

Catalytic activity of sub-units of glutamic dehydrogenase.

Dehydrogenae-reduced coenzyme difference spectra, their resolution and relationship to the stereospecificity of hydrogen transfer.

Ultraviolet Spectrophotometric Characterization of a Glutamate Dehydrogenase-reduced Coenzyme-α-Ketoglutarate Complex

The binding of α-ketoglutarate in a binary complex and in a ternary complex with NADP+ by l-glutamate dehydrogenase