Distribution of Fructose Diphosphate Aldolase Variants in Biological Systems

Lebherz, Herbert G.; Rutter, William J.

doi:10.1021/bi00829a016

Cited by 294 publications

(118 citation statements)

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“…During ontogenesis, the αα embryonic isoform remains distributed in most adult cell types, whereas a transition towards specific isoforms occurs in two tissues with high and fluctuating energy requirements : αγ and γγ in the nervous system, αβ and ββ in striated muscles [3][4][5]. It is noteworthy that, among glycolytic enzymes having isoforms with preferential expression in nervous or striated muscle tissues [6][7][8], the enolase isoenzyme family is unique for the strict celltype specificity of the β and γ subunits.…”

Section: Introductionmentioning

confidence: 99%

Biochemical characterization of the mouse muscle-specific enolase: developmental changes in electrophoretic variants and selective binding to other proteins

Меркулова

Lucas

Jabet

et al. 1997

Biochemical Journal

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The glycolytic enzyme enolase (EC 4.2.1.11) is active as dimers formed from three subunits encoded by different genes. The embryonic αα isoform remains distributed in many adult cell types, whereas a transition towards ββ and γγ isoforms occurs in striated muscle cells and neurons respectively. It is not understood why enolase exhibits tissue-specific isoforms with very close functional properties. We approached this problem by the purification of native ββ-enolase from mouse hindlimb muscles and by raising specific antibodies of high titre against this protein. These reagents have been useful in revealing a heterogeneity of the β-enolase subunit that changes with in i o and in itro maturation. A basic carboxypeptidase appears to be involved in generating an acidic β-enolase variant, and may regulate plasminogen binding by this subunit. We show for the

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Section: Introductionmentioning

confidence: 99%

Biochemical characterization of the mouse muscle-specific enolase: developmental changes in electrophoretic variants and selective binding to other proteins

Меркулова

Lucas

Jabet

et al. 1997

Biochemical Journal

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“…As one of the reasons for this glucose pattern, we have discussed isotope effects on several reactions of the pentose phosphate cycle, especially on the fructose-1,6-bisphosphate aldolase reaction. In order to verify this assumption we have now determined the kinetic and the equilibrium isotope effects on this reaction.We used for our experiments the well characterized Class I rabbit muscle aldolase (18,19), which belongs to the same class as the cytosolic plant enzyme (20,21). Rabbit muscle aldolase is a homotetramer with a molecular mass of 160 kDa, each subunit occurring in an ␣/␤ barrel (22).…”

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confidence: 99%

“…We used for our experiments the well characterized Class I rabbit muscle aldolase (18,19), which belongs to the same class as the cytosolic plant enzyme (20,21). Rabbit muscle aldolase is a homotetramer with a molecular mass of 160 kDa, each subunit occurring in an ␣/␤ barrel (22).…”

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confidence: 99%

Carbon Isotope Effects on the Fructose-1,6-bisphosphate Aldolase Reaction, Origin for Non-statistical 13C Distributions in Carbohydrates

Gleixner

Schmidt

1997

Journal of Biological Chemistry

119

107

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The kinetic and equilibrium isotope effects on the fructose-1,6-bisphosphate aldolase reaction have been determined using the rabbit muscle enzyme. The natural 13 C abundance for both atoms participating in the bond splitting were measured in position C-1 of dihydroxyacetone phosphate and glyceraldehyde 3-P after irreversible conversion to glycerol-3-P and 3-phosphoglycerate, respectively, and chemical degradation. The carbon isotope effects were determined comparing the 13 C content of the corresponding positions after partial and complete turnover, and after complete equilibration of the reactants. 13 (V max /K m ) on C-3 was 1.016 ؎ 0.007 and 0.997 ؎ 0.009 on position C-4, and the equilibrium isotope effects K 12 /K 13 on these positions were 1.0036 ؎ 0.0002 and 1.0049 ؎ 0.0001.The observed kinetic isotope effect on C-3 is discussed to originate from the formation of the enamine, which comes to equilibrium before the rate determining release of glyceraldehyde 3-P from the ternary complex. The equilibrium isotope effect is seen as the reason for an earlier-found relative 13 C enrichment in position C-3 and C-4 of glucose and for varying enrichments in 13 C of carbohydrates from different compartments of cells. The kinetic isotope effect is suggested to cause 13 C discriminations in the C-3 pool in context with the hexose formation in competition with other dihydroxyacetone phosphate turnover reactions.The relative enrichment of carbon-13 in the carboxyl group of amino acids, as observed by Abelson and Hoering (1) in 1961, was the first indication for the existence of non-statistical isotope distributions in biological compounds. Later results on acetic acid (2) and on acetoin (3) gave evidence that this observation was just one example of a common phenomenon. In order to find a general explanation for this observation Galimov (4) discussed that even in chemically unequilibrated systems, e.g. biological systems, a microscopic reversibility in enzymatic reactions is the origin for a thermodynamically ordered isotope distribution. The author's calculations could in fact explain some of the isotopic patterns of natural compounds known at that time. However, the presumption of a general thermodynamic equilibrium in biological systems is probably not realistic. In our opinion kinetic isotope effects on enzymatic reactions should be considered as primary causes for isotope discriminations. This has been proven for the primary CO 2 -fixing reactions (5-8). In secondary metabolism, the isotope effect on the pyruvate dehydrogenase reaction has been made responsible for the general depletion of 13 C in metabolites of acetyl-CoA, such as fatty acids or isoprenoids (9 -15).More detailed interpretations were possible when the total isotopic patterns of primary and secondary metabolites became available. Especially, our corresponding investigations on glucose indicated an enrichment of 13 C in positions C-3 and C-4, and a depletion of 13 C in positions C-1 and C-6 (Fig. 1) of this important primary metabolite (16). We have a...

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“…tribution (Lebherz & Rutter, 1969), and developmental expression (Weber, 1965). Vertebrate isozymes are thought to operate through a common mechanism involving Schiff base formation between the €-amino group of Lys-229 and the carbonyl carbon of the ketose (Horecker et al, 1972).…”

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confidence: 99%

Subunit interface mutants of rabbit muscle aldolase form active dimers

Beernink

Tolan

1994

Protein Science

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We report the construction of subunit interface mutants of rabbit muscle aldolase A with altered quaternary structure. A mutation has been described that causes nonspherocytic hemolytic anemia and produces a thermolabile aldolase (Kishi H et al., 1987, Proc Natl Acud Sci USA 8436234627). The disease arises from substitution of Gly for Asp-128, a residue at the subunit interface of human aldolase A. To elucidate the role of this residue in the highly homologous rabbit aldolase A, site-directed mutagenesis is used to replace Asp-128 with Gly, Ala, Asn, Gln, or Val. Rabbit aldolase Dl280 purified from Escherichia coli is found to be similar to human D128G by kinetic analysis, CD, and thermal inactivation assays. All of the mutant rabbit aldolases are similar to the wildtype rabbit enzyme in secondary structure and kinetic properties. In contrast, whereas the wild-type enzyme is a tetramer, chemical crosslinking and gel filtration indicate that a new dimeric species exists for the mutants. In sedimentation velocity experiments, the mutant enzymes exist as mixtures of dimer and tetramer at 4 "C. Sedimentation at 20 "C shows that the mutant enzymes are >99.5% dimeric and, in the presence of substrate, that the dimeric species is active. Differential scanning calorimetry demonstrates that T, values of the mutant enzymes are decreased by 12 "C compared to wild-type enzyme. The results indicate that Asp-128 is important for interface stability and suggest that 1 role of the quaternary structure of aldolase is to provide thermostability.

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Distribution of Fructose Diphosphate Aldolase Variants in Biological Systems

Cited by 294 publications

References 28 publications

Biochemical characterization of the mouse muscle-specific enolase: developmental changes in electrophoretic variants and selective binding to other proteins

Biochemical characterization of the mouse muscle-specific enolase: developmental changes in electrophoretic variants and selective binding to other proteins

Carbon Isotope Effects on the Fructose-1,6-bisphosphate Aldolase Reaction, Origin for Non-statistical 13C Distributions in Carbohydrates

Subunit interface mutants of rabbit muscle aldolase form active dimers

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