Oxalacetic acid activator

Krebs Cycle and Fatty Acid Oxidation. A possible role of Krebs cycle intermediates in supporting fatty acid oxidation is now apparent. Complete oxidation to CO2 requires oxalacetate to introduce acetyl CoA into the citric acid cycle. But even the formation of acetoacetate requires the continued generation of ATP to support the activation of fatty acids. The transfer of electrons from fatty acid to oxygen is coupled with phosphate esterification, so that fatty acid oxidation has the theoretical capacity to be self-supporting. In the crude systems that contain all of the essential factors for fatty acid oxidation, fatty acid activation must compete with other reactions for the available ATP, and maximum rates of oxidation occur only when additional ATP is generated through operation of the Krebs cycle. 

Sulfinylpyruvic acid accumulates as a result of the transaminating activity. It is an analog of oxalacetic acid, and like this compound, it is decomposed to pyruvate and SOs under the influence of Mn ". The reaction is analogous to the j3-decarboxylation of oxalacetate by Mn++. Mn++ also catalyzes the oxidation of SOj to S04 . As a consequence, reactions 5 and 6 of Fig. 2 are assumed to be nonenzymatic. 

Injection of hydrocortisone into the rat results in an approximately four fold increase in liver (but not kidney) tyrosine-a-ketoglutarate transaminase activity 374)- Corticosterone and cortisone were somewhat less effective. Interesting in this connection is the observation that injection of L-tyrosine increased the activity of tyrosine-a-ketoglutarate transaminase to about the same extent as hydrocortisone. Other amino acids had a much smaller stimulating effect which was attributed to adrenal cortical stress. In a preliminary report the addition of hydrocortisone to lymphocyte suspensions was found to inhibit glutamic-oxalacetic transaminase activity 376). 

Citric acid is a major end product of the oxidative metabolism of carbohydrate, ethanol, and acetic acid in many molds, e.g., Aspergillus niger. Evidence of the mechanism of citric acid formation is incomplete but the existing data are compatible with the assumption that citric acid arises, as an animal tissue, by condensation of oxalacetate with active acetic acid, as first proposed by Raistrick and Clark. Experiments with isotopic CO2 on Aspergillus suggest that the oxalacetate required for the synthesis of citrate can be formed by the carboxylation of pyruvate formed as an intermediate in the anaerobic fermentation.It is very... 

A carrier molecule containing four carbon atoms (the C4 unit) takes up a C2 unit (the activated acetic acid ), which is introduced into the cycle. The product is a six-carbon molecule (the C6 unit), citric acid, or its salt, citrate. CO2 is cleaved off in a cyclic process, so that a C5 unit is left this loses a further molecule of CO2 to give the C4 unit, oxalacetate. In the living cell, this process involves ten steps, which are catalysed by eight enzymes. However, the purpose of the TCA cycle is not the elimination of CO2, but the provision of reduction equivalents, i.e., of electrons, and... 

Biotin is a growth factor for many bacteria, protozoa, plants, and probably all higher animals. In the absence of biotin, oxalacetate decarboxylation, oxalosuccinate carboxylation, a-ketoglutarate decarboxylation, malate decarboxylation, acetoacetate synthesis, citrulline synthesis, and purine and pyrimidine syntheses, are greatly depressed or absent in cells (Mil, Tl). All of these reactions require either the removal or fixation of carbon dioxide. Together with coenzyme A, biotin participates in carboxylations such as those in fatty acid and sterol syntheses. Active C02 is thought to be a carbonic acid derivative of biotin involved in these carboxylations (L10, W10). Biotin has also been involved in... 

Chenoweth believes that an explanation of the above results may lie in the reactions occurring before the entrance of fatty acid metabolites into the citric acid cycle. Activated acetate, i.e. acetyl coenzyme A (AcCoA) is the end-product of fatty acid metabolism prior to its condensation with oxalacetate to form citrate. Possibly fluoro-fatty acids behave like non-fluorinated fatty acids. The end-product before the oxalacetate condensation could be the same for all three fluorinated inhibitors, viz. fluoroacetyl coenzyme A (FAcCoA). Fluorocitrate could then be formed by the condensation of oxalacetate with FAcCoA, thereby blocking the citric acid cycle. The specificity of antagonisms must therefore occur before entrance of the metabolites into the citric acid cycle. 

GS, and MDH were increased by HEf treatment of 1.79,1.50, and 1.49-fold, respectively. As a consequence of the increased activity of these enzymes, an increase in the amount of methionine, threonine, isoleucine, and lysine, amino acids derived from the oxalacetate pathway, were found. 

On the basis of this structural information, the pathway of the MPS reaction can be outlined as follows (Scheme 27) oxalacetate is incorporated into the active site of MPS in a similar way to that of pyruvate. Lewis acidity of the magnesium promotes decarboxylation to form the enolate anion, which is stabilized by an electron sink provided by the divalent cation. Steric congestion of the peptide backbone allows the 2-pyrone... 

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