Cycle, biochemical Krebs

Kreb s cycle Biochemical cycle in cellular aerobic metabolism where acetyl CoA is combined with oxaloacetate to form citric acid the resulting citric acid is converted into a number of other chemicals, eventually reforming oxaloacetate NADH, some ATP, and FADH2 are produced and carbon dioxide is released. 

Boris Pavlovich Belousov (1893-1970) looked for an inorganic analogue of the biochemical Krebs cycle. The investigations began in 1950 in a Soviet secret military institute. Belousov studied mixtures of potassium bromate with citric acid, and a small admixture of a catalyst a salt of cerium ions. He expected a monotonic transformation of the yellow Ce + ions into the colourless Ce +. Instead, he found oscillcilions of the colour of the solvent (colourless-yellow-colourless-... etc., also called by Russians vodka-cognac-vodka-... 

Kay J, Weitzman PDJ (editors) Krebs Citric Acid Cycle—Haifa Century and Still Turning. Biochemical Society, London, 1987. 

The biochemical classification of mitochondrial DNA is based on the five major steps of mitochondrial metabolism. These steps are illustrated in Figure 42-3 and divide mitochondrial diseases into five groups defects of mitochondrial transport, defects of substrate utilization, defects of the Krebs cycle, defects of the respiratory chain and defects of oxidation-phosphorylation coupling. 

Introduction of photoelectric cells led to the replacement of the Duboscq colorimeter and so to quantitative spectrophotometric methods of analysis which met biochemical requirements. This introduction of spectrophotometry as a routine procedure was one of the earliest technological advances underpinning the elucidation of biochemical pathways between 1930-1960. Micromanometric methods also became available about the same time, and offered a means to measure cell respiration. Manometry was developed in Warburg s laboratory in Berlin and was one of the main techniques used by H.A. Krebs in his studies on the citric acid and urea cycles (Chapters 5 and 6). 

H. Koenig, A. Patel, Biochemical Basis For Fluorouracil Neurotoxicity. The Role of Krebs Cycle Inhibition by Fluoroacetate , Arch. Neurol. 1970, 23, 155-160. 

It is possible to put forward a biochemical advantage for this unusual reaction in the activation of acetoacetate. The succinate that is produced in the reaction is further metabohsed to oxaloacetate, via the reactions of the Krebs cycle. Since acetyl-CoA requires oxaloacetate for formation of citrate and oxidation in the cycle, one product of... 

The biochemistry of the cycle was elucidated largely by Krebs Johnson (1937) Krebs was awarded the Nobel Prize in 1953. It is also called the citric acid cycle to acknowledge that others contributed to the biochemical details of the cycle. Acetyl-CoA is one substrate for the cycle but the amount in tissues is very small (2.5 nmol/g wet wt) and the maximum rate of the cycle in, for example,... 

Malaisse WJ, Zhang T-M, Verbruggen I, Willem R (1996) Enzyme to enzyme channeling of Krebs cycle metabolic intermediates in Caco-2 cells exposed to [2-13C]propionate. Biochem J 317 861-863... 

Biochemically, the pantothenate coenzymes are integral in the metabolism of carbohydrates, lipids, and nitrogen-containing compounds (185,186). They participate in the TCA or Krebs cycle, as well as fatty acid, phospholipid, sterol (cholesterol), and heme synthesis. The coenzymes mediate the exchange of 2-carbon (acetyl) and other acyl groups. They can serve as... 

K. Burton and H. A. Krebs, The free energy changes associated with the individual steps of the tricarboxylic acid cycle, glycolysis, alcoholic fermentation, and with the hydrolysis of the pyrophosphate group of adensosine triphosphate, Biochem.. /. 54, 94-107 (1953). 

Earlier biochemical studies had reported that the Krebs cycle in mitochondria are closely associated with the intramitochondrial precipitation of electron-dense mineral granules,138 which have been suggested as ACP containing OCP-carboxylate components.139 Previous studies have shown that succinate ions (00CC2H4C002 ) can be incorporated into the lattice of OCP,139-142 leading to the formation of the OCP-succinate (OCPS) compound.139 Consequently, OCPS prepared in vitro could serve as a model system to mimic the biomineralization process in mitochondria. The XRD... 

Urea is synthesized via the urea cycle (Fig. 18-1). In 1932, Krebs and Henseleit pubEshed data demonstrating that ornithine stimulates the synthesis of urea without stoichiometric consumption of this intermediate. This apparent catalytic function was determined to be the result of the cycEc nature of the pathway. This was a revolutionary idea since metabolic pathways were conceptualized as purely linear prior to the pubEcation of these observations. In the foUowing sections, we discuss the biochemical processes involved in urea formation. 

The tricarboxylic acid (TCA) cycle (also known as the citric acid cycle and the Krebs cycle) is a collection of biochemical reactions that oxidize certain organic molecules, generating CO2 and reducing the cofactors NAD and FAD to NADH and FADH2 [147], In turn, NADH and FADH2 donate electrons in the electron transport chain, an important component of oxidative ATP synthesis. The TCA cycle also serves to feed precursors to a number of important biosynthetic pathways, making it a critical hub in metabolism [147] for aerobic organisms. Its ubiquity and importance make it a useful example for the development of a kinetic network model. 

As for chloroplast membranes, various compounds in mitochondrial membranes accept and donate electrons. These electrons originate from biochemical cycles in the cytosol as well as in the mitochondrial matrix (see Fig. 1-9) —most come from the tricarboxylic acid (Krebs) cycle, which leads to the oxidation of pyruvate and the reduction of NAD+ within mitochondria. Certain principal components for mitochondrial electron transfer and their midpoint redox potentials are indicated in Figure 6-8, in which the spontaneous electron flow to higher redox potentials is toward the bottom of the figure. As for photosynthetic electron flow, only a few types of compounds are involved in electron transfer in mitochondria—namely, pyridine nucleotides, flavoproteins, quinones, cytochromes, and the water-oxygen couple (plus some iron-plus-sulfur-containing centers or clusters). 

The RQ for the conversion of glucose to fatty acids can be calculated from the biochemical considerations presented so far. This RQ would not be expected to occur in any living tissue or in any animal, because this RQ represents an extreme case in which there is no oxidation of fatty acids or of carbohydrates in the Krebs cycle. Where the rate of fatty acid synthesis is equal to the rate of fatty acid oxidation, the RQ would be expected to be 10. Where the rate of fatty acid synthesis is twice as great as the rate of fatty acid oxidation, the RQ would be greater than 1.0. One would not, however, expect to encounter a tissue in which there is only fatty acid synthesis and no fatty acid oxidation. 

Koenig H, Patel A. Biochemical basis for fluorouracil neurotoxicity. The role of Krebs cycle inhibition by flnor-oacetate. Arch Neurol 1970 23(2) 155-60. 

Biotransformation, especially phase I metabolic reactions, cannot be assumed to be synonymous with detoxification because some drugs (although a minority) and xenobiotics are converted to potentially toxic metabolites (e.g. parathion, fluorine-containing volatile anaesthetics) or chemically reactive intermediates that produce toxicity (e.g. paracetamol in cats). The term lethal synthesis refers to the biochemical process whereby a non-toxic substance is metabolically converted to a toxic form. The poisonous plant Dichapetalum cymosum contains monofluoroacetate which, following gastrointestinal absorption, enters the tricarboxylic acid (Krebs) cycle in which it becomes converted to monofluorocitrate. The latter compound causes toxicity in animals due to irreversible inhibition of the enzyme aconitase. The selective toxicity of flucytosine for susceptible yeasts (Cryptococcus neoformans, Candida spp.) is attributable to its conversion (deamination) to 5-fluorouracil, which is incorporated into messenger RNA. 

The second metabolic pathway which we have chosen to describe is the tricarboxylic acid cycle, often referred to as the Krebs cycle. This represents the biochemical hub of intermediary metabolism, not only in the oxidative catabolism of carbohydrates, lipids, and amino acids in aerobic eukaryotes and prokaryotes, but also as a source of numerous biosynthetic precursors. Pyruvate, formed in the cytosol by glycolysis, is transported into the matrix of the mitochondria where it is converted to acetyl CoA by the multi-enzyme complex, pyruvate dehydrogenase. Acetyl CoA is also produced by the mitochondrial S-oxidation of fatty acids and by the oxidative metabolism of a number of amino acids. The first reaction of the cycle (Figure 5.12) involves the condensation of acetyl Co and oxaloacetate to form citrate (1), a Claisen ester condensation. Citrate is then converted to the more easily oxidised secondary alcohol, isocitrate (2), by the iron-sulfur centre of the enzyme aconitase (described in Chapter 13). This reaction involves successive dehydration of citrate, producing enzyme-bound cis-aconitate, followed by rehydration, to give isocitrate. In this reaction, the enzyme distinguishes between the two external carboxyl groups... 

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