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PubMed1989

[Primary structure of histidine decarboxylase].

The results of investigation of the primary structure of the Histidine Decarboxylase Micrococcus sp. n. are reported. A comparison of the primary structure of the Histidine Decarboxylase Micrococcus sp. n. with that of the Lactobacillus 30a enzyme suggests the alignment with a 52% identity. It is therefore highly probable that two proteins have evolved from common ancestry. The conservative amino acid sequences with residues (pyruvate, cysteine) of the active center have been found.

Amino Acid Sequence↗
PubMed1984

Regulation of the tricarboxylic acid cycle pool size in heart muscle.

The anaplerotic mechanisms are mainly responsible for the intricate control of the size of the total tricarboxylic acid cycle pool, since cataplerotic fluxes leading out of the cycle can even increase during net synthesis of the cycle intermediates. Pyruvate carboxylation is probably the most important anaplerotic mechanism regulating the pool size of the citric acid cycle. However, not much is known of the regulation of pyruvate carboxylation or other ana- or cataplerotic mechanisms, and further research in this area is needed. The evidence accumulated so far indicates that regulation of the tricarboxylic acid cycle pool size serves to optimize energy transduction in heart muscle. This is seen at the level of the tricarboxylic acid cycle, where the tricarboxylic acid cycle intermediates can be taken to act in a catalytic manner to adjust the activities of the individual enzymes of the cycle at an appropriate level for a certain metabolic situation. On the other hand, increase in the mitochondrial citrate content serves as the mediator between the mitochondrial and cytosolic spaces and leads to diminished glucose utilization in glycolysis due to feed-back inhibition. However, net anaplerosis does not constitute a major energy-releasing system in the ischemic myocardium.

Acetyl Coenzyme A↗
PubMed1983

Inactivation of the 2-ketoglutarate and pyruvate dehydrogenase complexes of beef heart by branched chain keto acids.

Incubation of 2-ketoglutarate dehydrogenase complex with 2-ketoisovalerate, 2-keto-4-methylvalerate, or 2-keto-3-methylvalerate leads to the appearance of a lag phase and of a progressive loss of activity in subsequent measurements of the initial rate of oxidation of 2-ketoglutarate. In the case of 2-ketoisovalerate these effects are shown to be due to the formation of an isobutyryllipoate derivative of the enzyme, as a result of the very slow oxidation of 2-ketoisovalerate by the enzyme complex (Vmax congruent to 0.15% of that for 2-ketoglutarate). Incubation of the enzyme complex with 2-keto[14C]isovalerate or 2-keto[14C]glutarate results in comparable incorporation of radioactivity, amounting to 3.5 to 5.3 nmol of isobutyryl or succinyl residues per mg of protein in the complex. Isobutyryl residues are also incorporated in the enzyme during the simultaneous oxidation of both of these substrates. During the early phase of incubation of the complex with 2-ketoisovalerate the incorporation of isobutyryl residues is much faster than the loss of enzyme activity. This observation seems to support the suggestion that each 2-ketoglutarate decarboxylase subunit of the complex may catalyze the succinylation of more than one lipoate succinyltransferase subunit. Results are also presented showing the inactivation of pyruvate dehydrogenase complex on preincubation with 2-ketoisovalerate and of 2-ketoglutarate dehydrogenase complex with methylenecyclopropylpyruvate, the keto acid corresponding to the toxic amino acid hypoglycin. The relevance of covalent modifications of the two keto acid dehydrogenase complexes to the pathological manifestations of maple syrup urine disease are discussed.

Animals↗
PubMedDate not supplied

Carboxylation and anaplerosis in neurons and glia.

Anaplerosis, or de novo formation of intermediates of the tricarboxylic acid (TCA) cycle, compensates for losses of TCA cycle intermediates, especially alpha-ketoglutarate, from brain cells. Loss of alpha-ketoglutarate occurs through release of glutamate and GABA from neurons and through export of glutamine from glia, because these amino acids are alpha-ketoglutarate derivatives. Anaplerosis in the brain may involve four different carboxylating enzymes: malic enzyme, phosphoenopyruvate carboxykinase (PEPCK), propionyl-CoA carboxylase, and pyruvate carboxylase. Anaplerotic carboxylation was for many years thought to occur only in glia through pyruvate carboxylase; therefore, loss of transmitter glutamate and GABA from neurons was thought to be compensated by uptake of glutamine from glia. Recently, however, anaplerotic pyruvate carboxylation was demonstrated in glutamatergic neurons, meaning that these neurons to some extent can maintain transmitter synthesis independently of glutamine. Malic enzyme, which may carboxylate pyruvate, was recently detected in neurons. The available data suggest that neuronal and glial pyruvate carboxylation could operate at as much as 30% and 40-60% of the TCA cycle rate, respectively. Cerebral carboxylation reactions are probably balanced by decarboxylation reactions,, because cerebral CO2 formation equals O2 consumption. The finding of pyruvate carboxylation in neurons entails a major revision of the concept of the glutamine cycle.

Acyl Coenzyme A↗
PubMed1994

Secondary 18O and primary 13C isotope effects as a probe of transition-state structure for enzymatic decarboxylation of oxalacetate.

A new method for directly measuring 18O isotope effects on decarboxylation reactions has been developed. By running the reaction under high vacuum (10(-5) torr), CO2 leaves the solution before exchange with the oxygens of water to an extent greater than 2%. Thus, the method permits determination of 18O isotope effects with the precision of the isotope ratio mass spectrometer, and without the necessity of resorting to the remote label method and its attendant required syntheses. The method is used to determine 18O isotope effects for decarboxylation of oxalacetate (OAA) by Mg2+, and enzymatically by OAA decarboxylase from Pseudomonas putida; 13C isotope effects are also reported for this enzyme, as well as for decarboxylation of OAA by pyruvate kinase. Initial velocity patterns and pH profiles are reported for the P. putida enzyme, and all available data are used to discuss the kinetic and chemical mechanism of decarboxylation.

Carbon Isotopes↗
PubMed1998

Heterogeneity of mitochondrial protein biogenesis during primary leaf development in barley

The natural developmental gradient of light-grown primary leaves of barley (Hordeum vulgare L.) was used to analyze the biogenesis of mitochondrial proteins in relation to the age and physiological changes within the leaf. The data indicate that the protein composition of mitochondria changes markedly during leaf development. Three distinct patterns of protein development were noted: group A proteins, consisting of the E1 beta-subunit of the pyruvate dehydrogenase complex, ORF156, ORF577, alternative oxidase, RPS12, cytochrome oxidase subunits II and III, malic enzyme, and the alpha- and beta-subunits of F1-ATPase; group B proteins, consisting of the E1 alpha-subunit of the pyruvate dehydrogenase complex, isocitrate dehydrogenase, HSP70A, cpn60C, and cpn60B; and group C proteins, consisting of the four subunits of the glycine decarboxylase complex (P, H, T, and L proteins), fumarase, and formate dehydrogenase. All of the proteins increased in concentration from the basal meristem to the end of the elongation zone (20.0 mm from the leaf base), whereupon group A proteins decreased, group B proteins increased to a maximum at 50 mm from the leaf base, and group C proteins increased to a maximum at the leaf tip. This study provides evidence of a marked heterogeneity of mitochondrial protein composition, reflecting a changing function as leaf cells develop photosynthetic and photorespiratory capacity.

Journal Article↗
PubMed1977

Formation and dissimilation of oxalacetate and pyruvate Pseudomonas citronellolis grown on noncarbohydrate substrates.

Metabolism of lactate as a carbon source by Pseudomonas citronellolis occurred via a nicotinamide adenine dinucleotide (NAD)-independent L-lactate dehydrogenase, which was present in cells grown on DL-lactate but was not present in cells grown on acetate, aspartate, citrate, glucose, glutamate, or malate. The cells also possessed a constitutive, NAD-independent malate dehydrogenase instead of the conventional NAD-dependent malate dehydrogenase instead of the conventional NAD-dependent enzyme in the tricarboxylic acid cycle. Both enzymes were particulate and used dichlorophenolindo-phenol or oxygen as an electron acceptor. In acetate-grown cells, the activity of pyruvate dehydrogenase and NAD phosphate-linked malate enzyme decreased, cells grown on glucose or lactate. This was consistent with the need to maintain a supply of oxalacetate for metabolism of acetate via the tricarboxylic acid cycle. Changes in enzyme activities suggest that gluconeogenesis from noncarbohydrate carbon sources occurs via the malate enzyme (when oxalacetate decarboxylase is inhibited) or a combination of the NAD-independent malate dehydrogenase and oxalacetate decarboxylase.

Acetates↗
PubMed1984

Glycolate metabolism is under nitrogen control in chlorella.

The utilization of nitrate and ammonia as nitrogen sources had different effects on the metabolism of glycolate in Cholorella sorokiniana. During photolithotrophic growth with nitrate as nitrogen source, glycolate was metabolized via the glycine-serine pathway. Ammonia, produced as a result of glycolate metabolism, was reassimilated by glutamine synthetase. Two isoforms of this enzyme were present at different relative abundance in C. sorokiniana wild type and in a mutant with an increased capacity for the metabolism of glycolate (strain OR).During photolithotrophic growth in the presence of ammonia as sole nitrogen source, several lines of evidence indicated that glycolate was metabolized to malate, pyruvate, tricarboxylic acid cycle intermediates and related amino acids in C. sorokiniana wild-type cells. Malate synthase was induced and glycine decarboxylase and serine-glyoxylate aminotransferase were repressed in cells grown with ammonia. An inverse correlation was observed between aminating NADPH-glutamate dehydrogenase and the in vivo glycine decarboxylation rate.

Journal Article↗
PubMed1975

Inhibition of histidine, decarboxylation in vivo by 2-hydroxy-5-carbomethoxybenzyloxyamine, a new, potent inhibitor of histidine decarboxylase.

Measurements of the rate of expiration of 14CO2 were carried out after the injection into rats of 14C-histidine labeled in the carboxyl group (C-His) or in the imidazole ring (R-His). Intraperitoneal administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, a new potent inhibitor of histidine decarboxylase, reduced the rate of 14CO2 production from C-His and R-His in a dose-dependent manner. The metabolism of C-His was more affected than that of R-His. The inhibitor had no effect on the production of 14CO2 from 14C-urocanic acid, 14C-dopa or 14C-glutamic acid. Rats given 2-hydroxy-5-carbomethoxybenzyloxyamine (100 mg/kg) by the intraperitoneal route had diminished histidine decarboxylase activity of stomach (96 percent decrease), but did not have any change in the activities of histidase, urocanase or histidine-pyruvate aminotransferase of liver. After the administration of histidine (500 mg/kg), the level of this amino acid in serum remained elevated somewhat longer in inhibitor-treated animals than in the controls. The temporary rise in serum histidine relative to controls that were also histidine-loaded is considered to reflect the decreased rate of uptake of histidine into the tissues, and also a decreased rate of decarboxylation of histidine in certain organs. After the administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, the decreased rate of 14CO2 production from injected R-His and the delayed disappearance of histidine from the serum after a histidine load were considered to reflect mainly the decreased rate of histidine uptake into the tissues. The decreased rate of formation of 14CO obtained with C-His appeared to result from inhibition of both uptake and decarboxylation of histidine.

Animals↗
PubMed1989

Pyruvoyl-dependent histidine decarboxylase. Active site structure and mechanistic analysis.

The structure of the pyruvoyl-dependent histidine decarboxylase has been refined to 2.5 A resolution by the methods of x-ray crystallography from crystals grown at pH 4.8, where the enzyme is optimally active. Models of the active site with and without the bound substrate analog, histidine methyl ester (HisOMe), or the product, histamine, have been produced. Comparison of native and ligand-bound structures reveals no widespread differences in conformation but does reveal motion of a few key residues (Tyr-62', Ile-59', Ser-81) upon binding of HisOMe in the active site. The HisOMe binds with the appropriate alpha-carbon-carbon bond oriented as required to facilitate the formation of the transition state. The binding site contains two pockets, one for the imidazole group, and another for the -COOMe group. In the imidazole pocket, the imidazolium group forms hydrogen bonds with two neighboring carboxylates, Asp-63' and the carboxyl terminus of the beta chain, Ser-81. Hydrophobic contacts are also observed. The carboxylate pocket is predominantly hydrophobic as predicted by Alston and Abeles (Alston, T. A., and Abeles, R. H. (1987) Biochemistry 26,4082-4085), but includes one carboxyl group, that of Glu-197, about 3.5 A from the substrate carboxylate. If Glu-197 is protonated under these conditions, it could serve as the proton donor following decarboxylation; if it is ionized under these conditions, its carboxylate group is appropriately placed to enhance the lability of the substrate carboxylate ion by providing a "push" in promoting the flow of electrons that results in decarboxylation. These and other structural features of the binding complex are discussed as they relate to a proposed mechanism of decarboxylation.

Amino Acid Sequence↗
PubMed1980

The regulation of glucose and pyruvate formation from glutamine and citric-acid-cycle intermediates in the kidney cortex of rats, dogs, rabbits and guinea pigs.

The suppression by 3-mercaptopicolinate of gluconeogenesis from glutamine or 2-oxoglutarate in rat or dog kidney tubules did not affect the amount of these substrates undergoing complete oxidation. Furthermore, 3-mercaptopicolinate caused an accumulation of lactate in dog tubules. 3-Mercaptopicolinate abolished both gluconeogenesis and substrate oxidation in tubules from rabbit and guinea-pig kidney. These results imply the presence of an alternative pathway to phosphoenolpyruvate carboxykinase/pyruvate kinase for the production of pyruvate from citric-acid-cycle intermediates in the kidney cortex of rats and dogs but not in that of rabbits or guinea pigs. Oxaloacetate decarboxylase (present in the kidney cortex of all four species) or 'malic' enzyme (present in rat and dog but absent in rabbit and guinea-pig kidney cortex) could function in this role. Our observations indicate that 'malic' enzyme is probably implicated in this phenomenon. The lactate production observed in dog tubules in the presence of 3-mercaptopicolinate can be suppressed when aspartate formation is inhibited by 2-amino-4-methoxy-trans-but-3-enoic acid. This suggests that the provision of cytosolic NADH from citric-acid-cycle intermediates is facilitated by accumulation of aspartate acting as a 'sink' for cytosolic oxaloacetate.

Animals↗
PubMed1984

Unusual C3 and C4 metabolism in the chemoautotroph Alcaligenes eutrophus.

Phosphoenolpyruvate (PEP) carboxykinase was identified to be the only C3-carboxylating enzyme in Alcaligenes eutrophus. The enzyme requires GDP or inosine diphosphate (GTP or inosine triphosphate) for activity. Pyruvate- and other PEP-dependent CO2-fixing enzyme activities were not detected, regardless of whether the cells were grown autotrophically or heterotrophically. It is suggested that two pathways are present in the organism for the formation of PEP from C4 dicarboxylic acids. Besides decarboxylation of oxaloacetate by PEP carboxykinase, the consecutive action of NADP+-malic enzyme and PEP synthetase can also accomplish this synthesis. An oxaloacetate decarboxylase activity observed in the cell extracts may also contribute to the latter route. The properties of a mutant deficient in PEP synthetase supported the biochemical data. This mutant was unable to grow on pyruvate or lactate and grew slower than the wild type on direct or indirect metabolites of the tricarboxylic acid cycle such as succinate, glutamate, or acetate. Growth on fructose and autotrophic growth were not affected by the enzyme defect. The findings suggest that, depending on the growth substrate utilized, PEP carboxykinase can serve a dual physiological function in A. eutrophus, an anaplerotic function in oxaloacetate synthesis from PEP, or a gluconeogenic function in PEP synthesis from oxaloacetate.

Alcaligenes↗
PubMed1968

Diaminopimelate decarboxylase of sporulating bacteria.

The meso-diaminopimelate (DAP) decarboxylase of Bacillus licheniformis, a pyridoxal phosphate-requiring enzyme, was stabilized in vitro by 0.15 m sodium phosphate buffer (pH 7.0) containing 1 mm 2,3-dimercaptopropan-1-ol, 100 mug of pyridoxal phosphate per ml, and 3 mm DAP. When the meso-DAP concentration was varied, the enzyme in cell-free extracts of B. licheniformis exhibited Michaelis-Menten kinetics. Pyridoxal phosphate was the only pyridoxine derivative which acted as a cofactor. The enzyme was subject to both inhibition and repression by l-lysine. The inhibitory effect of lysine was on the K(m) (meso-DAP). A maximum repression of about 20% was obtained. No significant inhibition or activation was produced by cadaverine, dipicolinic acid, phenylalanine, pyruvate, ethylenediamine-tetraacetate, adenosine triphosphate, adenosine diphosphate, or adenosine monophosphate. When B. licheniformis was grown in an ammonium lactate-glucose-salts medium, an increase in DAP decarboxylase specific activity occurred during cellular growth with a maximal specific activity at the end of the exponential phase. As soon as growth ceased, the specific activity of the enzyme decreased to approximately one-half of the maximal specific activity and remained at this level thereafter. When B. cereus was grown in complex media, there was an increase in DAP decarboxylase specific activity up to the end of the exponential phase. Thereafter, the specific activity decreased to a nondetectable level in 4 hr. Dipicolinic acid synthesis was first detected 15 min later and was essentially complete after an additional 2.5 hr. The significance of the disappearance of DAP decarboxylase in B. cereus was discussed with regard to control of dipicolinic acid and spore mucopeptide biosynthesis.

Bacillus↗
PubMed1981

Effects of pH and Sugar on Acetoin Production from Citrate by Leuconostoc lactis.

The relationship between acetoin production and citrate utilization in Leuconostoc lactis NCW1 was studied. In a complex medium the organism utilized citrate at neutral pH (initial pH, 6.3) and at acid pH (initial pH, 4.5) but produced nine times more acetoin at the latter pH. In resting cells the utilization of citrate was optimum at pH 5.3. Production of acetoin as a function of citrate utilization increased as the pH decreased, and at pH 4.3 all of the citrate utilized was recovered as acetoin. Glucose (10 mM) and lactose (10 mM) markedly stimulated citrate utilization but totally inhibited acetoin production in glucose- and lactose-grown cells. Addition of glucose to cells actively metabolizing citrate caused an immediate increase in citrate uptake and a reduction in the level of acetoin. The apparent K(m) values of lactic dehydrogenase for pyruvate were 1.05, 0.25, and 0.15 mM at pH 7.5, 6.5, and 5.0, respectively. Several heterofermentation intermediates inhibited alpha-acetolactate synthetase and decarboxylase activities. The implications of these results in regulating acetoin formatin are discussed.

Journal Article↗