Krebs TCA cycle

The Tricarboxylic acid cycle is in many ways the central pathway of metabolism, both catabolically and anabolically it is involved in the breakdown and synthesis of a variety of compounds. The oxidative breakdown of the acetyl group of acetyl CoA (Fig. 9.5). 

First condense the acetyl group with a four carbon carrier to get a six carbon triacid. This is then rearranged and oxidized with loss of carbon dioxide to give a five carbon di-acid ketol very similar to pyruvate in structure. An irreversible DH Complex then creates a four carbon CoA derivative with the release of a second carbon dioxide. At this point it appears that acetyl has been released as carbon dioxide, however, the carrier has been reduced, and modified. A series of reactions now regenerates the original carrier. 

The first reaction of the cycle is an aldol condensation catalyzed by  

Note that the enzyme catalyst enables the coupling of two chemically independent reactions the aldol condensation (with free energy change of about zero) to the very favourable hydrolysis of the CoA thiol ester bond which drives the overall reaction far towards product. Essentially, we have used an ATP s worth of energy to drive the reaction to completion. 

Unfortunately the resulting citrate is a tertiary alcohol which cannot be readily oxidized. Aconitase catalyzes the rearrangement of citrate to give an oxidizable secondary alcohol. This reaction involves an elimination/addition sequence, catalyzed by an iron-sulphur cluster (Fe4S4), with an alkene intermediate, cis-Aconitate  

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Glycolysis and the Krebs TCA cycle as models of control of metabolic pathways... 

It can enter glycolysis and the Krebs TCA cycle to be oxidized into CO2 and H2O. This is the ultimate fate for glucose. 

C. Velot, M B. Mixon, M. Teige, and P.A. Srere. 1997. Model of a quinary structure between Krebs TCA cycle enzymes A model for the metabolon Biochemistry 36 14271-14276. (PubMed)... 

Fluoroacetate. This naturally occurring toxicant is an analogue of acetate and is incorporated into acetylCoA (fluoroacetate) and hence into Krebs (TCA) cycle as fluorocitrate. This blocks the enzyme aconitase as the fluorine atom cannot be removed. The TCA cycle is blocked and citrate accumulates. The mitochondrial energy supply is disrupted hence cardiac damage occurs. Lack of oxaloacetate will allow ammonia to accumulate leading to convulsions. 

The initial stages of catabolism result in the conversion of both fats and carbohydrates into acetyl groups that are bonded through a thioester link to coenzyme A. Acetyl CoA then enters the next stage of catabolism—the citric acid cycle, also called the tricarboxylic acid (TCA) cycle, or Krebs tycle, after Hans Krebs, who unraveled its complexities in 1937. The overall result of the cycle is the conversion of an acetyl group into two molecules of C02 plus reduced coenzymes by the eight-step sequence of reactions shown in Figure 29.12. 

Wachtcrshauser s prime candidate for a carbon-fixing process driven by pyrite formation is the reductive citrate cycle (RCC) mentioned above. Expressed simply, the RCC is the reversal of the normal Krebs cycle (tricarboxylic acid cycle TCA cycle), which is referred to as the turntable of metabolism because of its vital importance for metabolism in living cells. The Krebs cycle, in simplified form, can be summarized as follows ... 

Pathways can be illustrated in a metabolic map as linear, branched or cyclic processes (Figure 1.3) and are often compartmentalized within particular subcellular location glycolysis in the cytosol and the Krebs tricarboxylic acid (TCA) cycle in... 

The situation is simpler for odd numbered fatty acyl derivatives as [3-oxidation proceeds normally until a 5-carbon unit remains, rather than the usual 4-carbon unit. The C5 moiety is cleaved to yield acetyl-CoA (C2) and propionyl-CoA (C3). Propionyl CoA can be converted to succinyl CoA and enter the TCA cycle so the entire molecule is utilized but with a slight reduction in ATP yield as the opportunity to generate two molecules of NADH by isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase is lost because succinyl-CoA occurs after these steps in the Krebs cycle (Figure 7.18). 

In stage three, the citric add (Krebs, or tricarboxylic acid [TCA]) cycle oxidizes acetyl CoA to COj- The energy released in this process is primarily conserved by reducing NAD to NADH or FAD to FADHj. 

The tricarboxylic acid cycle (TCA cycle, also known as the citric acid cycle or Krebs cycle) is a cyclic metabolic pathway in the mitochondrial matrix (see p. 210). in eight steps, it oxidizes acetyl residues (CH3-CO-) to carbon dioxide (CO2). The reducing equivalents obtained in this process are transferred to NAD"" or ubiquinone, and from there to the respiratory chain (see p. 140). Additional metabolic functions of the cycle are discussed on p. 138. 

A The TCA cycle, also called the Krebs cycle, is the final destination for metabolism of fuel molecules. 

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. 

TCA CYCLE, (tricarboxylic acid cycle Krebs cycle or citric acid cycle). A series of enzymatic reactions occurring in living cells of aerobic... 

When the oxidation of substantial amounts of pyruvate was blocked by malonate, stoichiometric amounts of pyruvate would react if either oxaloacetate or its precursors, malate or fumarate, was added. None of the precursors to succinate in the chain was effective in this regard. This strongly supported Krebs hypothesis that oxidation of pyruvate involved its condensation with oxaloacetate and the subsequent series of conversions in the chain described by Krebs. The Krebs cycle in its originally proposed form is shown in figure 13.3. It is also known as the tricarboxylic acid (TCA) cycle or the citrate cycle. 

Original tricarboxylic acid (TCA) cycle proposed by Krebs. This cycle is also called the citrate cycle, or the Krebs cycle. To start the cycle in operation, pyruvate loses one of its carbons and condenses with a four-carbon dicarboxylic acid, oxaloacetic acid, to form a six-carbon tricarboxylic acid, citrate. In one turning of the cycle, two carbons are lost as C02, thus returning the citrate to oxaloacetate. The conversion blocked by malonate is indicated by a red bar. 

Suppl.) K73, 1980. A well-rounded review of TCA cycle regulation as a contemporary research theme from a symposium dedicated to Hans Krebs. 

The Urea Cycle and the TCA Cycle Are Linked by the Krebs Bicycle... 

The fumarate released in the urea cycle links the urea cycle with the TCA cycle. This fumarate is hydrated to malate, which is oxidized to oxaloacetate. The carbons of oxaloacetate can stay in the TCA cycle by condensation with acetyl-CoA to form citrate, or they can leave the TCA cycle either by gluconeogenesis to form glucose or by transamination to form aspartate as shown in figure 22.9. Because Krebs was involved in the discoveries of both the urea cycle and the TCA cycle, the interaction between the two cycles shown in figure 22.9 is sometimes referred to as the Krebs bicycle. 

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