Citric acid cycle compounds

Useful for such compounds as sugars, phenols, alcohols, amines, thiols, steroids especially recommended for citric acid cycle compounds and amino acids reaction is often carried out in pyridine or dimethyl formamide (the latter being preferred for 17-keto steroids) care must be taken to eliminate moisture lowest silyl donating strength of all common silating reagents... 

It had been known that propionic acid could give rise, in the presence of liver cell fractions, to citric acid cycle compounds and eventually carbohydrates. 

A large number of biological reactions involve prochiral compounds. One of the steps in the citric acid cycle by which food is metabolized, for instance, is... 

The catabolism of proteins is much more complex than that of fats and carbohydrates because each of the 20 amino acids is degraded through its own unique pathway. The general idea, however, is that the amino nitrogen atom is removed and the substance that remains is converted into a compound that enters the citric acid cycle. 

The primary fate of acetyl CoA under normal metabolic conditions is degradation in the citric acid cycle to yield C02. When the body is stressed by prolonged starvation, however, acetyl CoA is converted into compounds called ketone bodies, which can be used by the brain as a temporary fuel. Fill in the missing information indicated by the four question marks in the following biochemical pathway for the synthesis of ketone bodies from acetyl CoA ... 

Fatty acids with an odd number of carbon atoms are oxidized by the pathway of P-oxidation, producing acetyl-CoA, until a three-carbon (propionyl-CoA) residue remains. This compound is converted to succinyl-CoA, a constiment of the citric acid cycle (Figure 19-2). Hence, the propionyl residue from an odd-chain frtty acid is the only part of a frtty acid that is glucogenic. 

L-ascorbic acid and, 25 751 as chelating agent, 5 731 in cocoa shell from roasted beans, 6 357t Oxalic-acid-catalyzed novolacs, in molding compounds, 75 786 Oxalic acid esterification, 72 652 Oxaloacetic acid, in citric acid cycle, 6 633 Oxalosuccinic acid, in citric acid cycle, 6 633... 

The key to unraveling the toxicity of fluoracetate came from observations of Buffa and Peters (1949) that in animals treated with FAc, considerable quantities of citrate accumulated in some tissues. Oxygen uptake was also diminished. The citric acid cycle was thus implicated as the site of inhibition. Fluorcitrate was then isolated from the affected tissues. It was found to be a powerful competitive inhibitor of aconitase, thus blocking citrate oxidation. The suggestion was therefore made that fluoracetate was toxic not in itself, but because it was metabolized in cells via fluoracetyl CoA to give a toxic derivative, an example of lethal synthesis —the capacity of organisms to metabolize nontoxic compounds and convert them to potentially lethal products. 

And so it happened that the detection of isotopic carbon from UC02 in the [i carboxyl group of a-ketoglutarate was celebrated as a discovery of CO 2 fixation in animal tissues, and was taken as evidence that there wasn t any citric acid in the citric acid cycle. A citric acid precursor of a-ketoglutarate would have to be labelled as in compound 1... 

Figure 16.1 a schematic representation illustrating the chemical reactions that interconvert small molecules in cells. Each dot represents a compound and the lines that connect them represent reactions. The heavy dots and lines down the center of the maze reflect the glycolytic pathway and the heavy circle near the bottom of the maze reflects the citric acid cycle. ( 2007 From Molecular Biology of the Cell, 5th Edition, by Alberts et al. Reproduced by permission of Garland Science/Taylor Francis, EEC.)... 

The Krebs cycle is sometimes still referred to as the citric acid cycle, citric acid being one of the intermediates involved, and even the tricarboxylic acid cycie, in that several of the intermediates are tri-acids. As the name suggests, the process is a cycle, so that there is a reasonably constant pool of intermediates functioning in an organism, and material for degradation is processed via this pool of intermediates. Overall, though, the material processed does not increase the size of the pool. The compound... 

The toxicity of fluoroacetic acid and of its derivatives has played an historical decisive role at the conceptual level. Indeed, it demonstrates that a fluorinated analogue of a natural substrate could have an activity profile that is far different from that of the nonfluorinated parent compound. The toxicity of fluoroacetic acid is due to its ability to block the citric acid cycle (Krebs cycle), which is an essential process of the respiratory chain. The fluoroacetate is transformed in vivo into 2-fluorocitrate by the citrate synthase. It is generally admitted that aconitase (the enzyme that performs the following step of the Krebs cycle) is inhibited by 2-fluorocitrate the formation of aconitate through elimination of the water molecule is a priori impossible from this substrate analogue (Figure 7.1). 

When compounds enriched in the heavy-carbon isotope 13C and the radioactive carbon isotopes nC and 14C became available about 60 years ago, they were soon put to use in tracing the pathway of carbon atoms through the citric acid cycle. One such experiment initiated the controversy over the role of citrate. Acetate labeled in the carboxyl group (designated [1-14C] acetate) was incubated aerobically with an animal tissue preparation. Acetate is enzymatically converted to acetyl-CoA in animal tissues, and the pathway of the... 

The citric acid cycle (Krebs cycle, TCA cycle) is a nearly universal central catabolic pathway in which compounds derived from the breakdown of carbohydrates, fats, and proteins are oxidized to C02, with most of the energy of oxidation temporarily held in the electron carriers FADH2 and NADH. During aerobic metabolism, these electrons are transferred to 02 and the energy of electron flow is trapped as ATP. 

Besides acetyl-CoA, any compound that gives rise to a four- or five-carbon intermediate of the citric acid cycle—for example, the breakdown products of many amino acids—can be... 

When intermediates are shunted from the citric acid cycle to other pathways, they are replenished by several anaplerotic reactions, which produce four-carbon intermediates by carboxylation of three-carbon compounds these reactions are catalyzed by pyruvate carboxylase, PEP carboxykinase, PEP carboxylase, and malic enzyme. Enzymes that catalyze carboxylations commonly employ biotin to activate C02 and... 

Energy Yield from the Citric Acid Cycle The reaction catalyzed by succinyl-CoA synthetase produces the high-energy compound GTP. How is the free energy contained in GTP incorporated into the cellular ATP pool ... 

The ketone bodies—acetone, acetoacetate, and D-/3-hydroxybutyrate—are formed in the liver. The latter two compounds serve as fuel molecules in extrahepatic tissues, through oxidation to acetyl-CoA and entry into the citric acid cycle. 

After removal of their amino groups, the carbon skeletons of amino acids undergo oxidation to compounds that can enter the citric acid cycle for oxidation to C02 and H20. The reactions of these pathways require a number of cofactors, including tetrahydrofolate and 5-adenosylmethionine in one-carbon transfer reactions and tetrahydrobiopterin in the oxidation of phenylalanine by phenylalanine hydroxylase. 

Carbohydrate metabolism in a typical plant cell is more complex in several ways than that in a typical animal cell. The plant cell carries out the same processes that generate energy in animal cells (glycolysis, citric acid cycle, and oxidative phosphorylation) it can generate hexoses from three- or four-carbon compounds by glu-coneogenesis it can oxidize hexose phosphates to pentose phosphates with the generation of NADPH (the ox-... 

As a result of metabolic reactions an isotope may appear at more than one position in a product, yielding two or more isotope isomers or isotopomers. These are seen individually by NMR spectroscopy and the concentration and isotope labeling patterns of the labeled compounds can be followed over a period of time. The use of this isotopomer analysis in studies of the citric acid cycle is illustrated in Box 17-C and its use in studies of glucose metabolism is considered in Chapter 17, Section L. 

One of the first persons to study the oxidation of organic compounds by animal tissues was T. Thunberg, who between 1911 and 1920 discovered about 40 organic compounds that could be oxidized by animal tissues. Salts of succinate, fumarate, malate, and citrate were oxidized the fastest. Well aware of Knoop s (3 oxidation theory, Thunberg proposed a cyclic mechanism for oxidation of acetate. Two molecules of this two-carbon compound were supposed to condense (with reduction) to succinate, which was then oxidized as in the citric acid cycle to oxaloacetate. The latter was decarboxylated to pyruvate, which was oxidatively decarboxylated to acetate to complete the cycle. One of the reactions essential for this cycle could not be verified experimentally. It is left to the reader to recognize which one. 

One of the simplest biochemical addition reactions is the hydration of carbon dioxide to form carbonic acid, which is released from the zinc-containing carbonic anhydrase (left, Fig. 13-1) as HC03-. Aconitase (center, Fig. 13-4) is shown here removing a water molecule from isocitrate, an intermediate compound in the citric acid cycle. The H20 that is removed will become bonded to an iron atom of the Fe4S4 cluster at the active site as indicated by the black H20. An enolate anion derived from acetyl-CoA adds to the carbonyl group of oxaloacetate to form citrate in the active site of citrate synthase (right, Fig. 13-9) to initiate the citric acid cycle. 

The primary substrate of the citric acid cycle is acetyl-CoA. Despite many references in the biochemical literature to substrates "entering" the cycle as oxaloacetate (or as one of the immediate precursors succinate, fumarate, or malate), these compounds are not consumed by the cycle but are completely regenerated hence the term regenerating substrate, which can be applied to any of these four substances. A prerequisite for the operation of a catalytic cycle is that a regenerating substrate be readily available and that its concentration... 

Among the most deadly of simple compounds is sodium fluoroacetate. The LD50 (the dose lethal for 50% of animals receiving it) is only 0.2 mg/kg for rats, over tenfold less than that of the nerve poison diisopropylphosphofluoridate (Chapter 12).a b Popular, but controversial, as the rodent poison "1080," fluoroacetate is also found in the leaves of several poisonous plants in Africa, Australia, and South America. Surprisingly, difluoroacetate HCF2-COO is nontoxic and biochemical studies reveal that monofluoroacetate has no toxic effect on cells until it is converted metabolically in a "lethal synthesis" to 2R,3R-2-fluorocitrate, which is a competitive inhibitor of aconitase (aconitate hydratase, Eq. 13-17).b This fact was difficult to understand since citrate formed by the reaction of fluorooxalo-acetate and acetyl-CoA has only weak inhibitory activity toward the same enzyme. Yet, it is the fluorocitrate formed from fluorooxaloacetate that contains a fluorine atom at a site that is attacked by aconitase in the citric acid cycle. 

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