Kreb’s cycle

Rice bran is the richest natural source of B-complex vitamins. Considerable amounts of thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5) and pyridoxin (B6) are available in rice bran (Table 17.1). Thiamin (Bl) is central to carbohydrate metabolism and kreb s cycle function. Niacin (B3) also plays a key role in carbohydrate metabolism for the synthesis of GTF (Glucose Tolerance Factor). As a pre-cursor to NAD (nicotinamide adenine dinucleotide-oxidized form), it is an important metabolite concerned with intracellular energy production. It prevents the depletion of NAD in the pancreatic beta cells. It also promotes healthy cholesterol levels not only by decreasing LDL-C but also by improving HDL-C. It is the safest nutritional approach to normalizing cholesterol levels. Pyridoxine (B6) helps to regulate blood glucose levels, prevents peripheral neuropathy in diabetics and improves the immune function. 

Fig. 6.6 The modem version of the tricarboxylic acid cycle (Kreb s cycle).

An experimenter labeled oxaloacetate with UC at the carboxyl carbon farthest from the keto group. The oxaloacetate was allowed to undergo the portion of the Kreb s cycle depicted in Figure 2. The acetyl group donated by acetyl CoA is not removed during the Kreb s cycle. The experimenter found that all of the label emerged in the CO, of the second decarboxylation. 

The acetyl CoA molecules feed the Kreb s cycle, which is also known as the citric acid cycle or the tricarboxylic acid (TCA) cycle. Thus, one molecule of glucose can drive two rounds of the Kreb s cycle, whereas one molecule of stearic acid can drive nine rounds. The Kreb s cycle is the principal aerobic energy-producing pathway. Each turn of the Kreb s cycle affords one ATP5 molecule, three NADH molecules, and one QH2 molecule. Most of the energy produced directly from the Kreb s cycle is in NADH and QH2, both of which require oxygen to convert their stored energy into ATP. 

Orally administered L-carnitine and propionyl-L-carnitine may have metabolic benefits by providing an additional source of carnitine to buffer the cellular acyl CoA pool. In this way, carnitine may enhance glucose oxidation under ischemic conditions and improve energy metabolism in the ischemic skeletal muscle. Propionyl-CoA generated from propionyl-L-carnitine may also improve oxidative metabolism through its anaphoretic actions in priming the Kreb s cycle, secondary to succinyl-CoA production. 

A specific transport protein, the carnitine-acylcarnitine translocase, moves the fatty acylcarnitine into the mitochondrial matrix while returning carnitine from the matrix to the cytoplasm. Once inside the mitochondria, another enzyme, carnitine palmitoyltransferase II (CPT II), located on the matrix side of the mitochondrial inner membrane, catalyzes the reconversion of fatty acylcarnitine to fatty acyl-CoA. Intramitochondrial fatty acyl-CoA then undergoes (3-oxidation to generate acetyl-CoA.Acetyl-CoA can enter the Kreb s cycle for complete oxidation or, in the liver, be used for the synthesis of acetoacetate and P-hydroxybutyrate (ketone bodies). 

Figure 28-7. The metabolism of branched-chain amino acids and odd-chain fatty acids via propionyl-CoA. Propionyl-CoA is converted to D-methylmalonyl-CoA by propionyl-CoA carboxylase. D,L-Methylmalonyl-CoA racemase catalyzes the conversion of D-methylmalonyl-CoA to L-methylmalonyl-CoA. L-methyl malonyl-CoA mutase, an adenosyicobalamin-requiring enzyme, converts L-methylmalonyl-CoA to succinyl-CoA.TCA cycle is citric acid cycle or Kreb s cycle.

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. 

Stage II breakdown of products of Stage I to. pyruvate, acetyl CoA, and/or intermediates of the Kreb s Cycle... 

Stage III Breakdown of Acetyl CoA by the Kreb s Cycle into carbon dioxide and water with the production of reducing equivalents (NADH etc.)... 

Note that because all catalysts (oxaloacetate, enzymes etc.) must be regenerated in looking at the overall operation of the cycle, only the acetyl group of acetyl-CoA can be oxidized completely. Some intermediates, such as citrate, can be partially oxidized, but Kreb s cycle intermediate catabolism requires leaving the cycle at oxaloacetate and then returning as acetyl-CoA. It requires leaving the mitochondria for some reactions, and since the extremely low concentrations of oxaloacetate don t allow its efficient transport across the mitochondrial membrane (the Km of the carrier is much higher than [oxaloacetate]), malate is the species which actually leaves the mitochondria. 

The second stage of cellular respiration, called the Kreb s cycle, also has several steps. The overall result is the oxidation of pyruvic acid to form CO2, as shown in the following equation. 

D. It produces the oxygen necessary for the reactions involved in the Kreb s cycle. 

Fluoroacetate produces its toxic action (after conversion to fluorocitrate) by inhibiting the Kreb s cycle. The compound is incorporated into fluoroacetyl coenzyme A, which condenses with oxaloacetate... 

Thallium s mechanism of toxicity is related to its ability to interfere with potassium ion functions. Thallium interferes with energy production at essential steps in glycolysis, the Kreb s cycle, and oxidative phosphorylation. Other effects include inhibition of sodium-potassium-adenosine triphosphatase and binding to sulfhydryl groups. 

Actively respiring fungal cells possess a distinct mitochondrion, which has been described as the power-house of the cell (Fig. 4.2). The enzymes of the tricarboxylic acid cycle (Kreb s cycle) are located in the matrix of the mitochondrion, while electron transport and oxidative phosphorylation occur in the mitochondrial inner membrane. The outer membrane contains enzymes involved in lipid biosynthesis. The mitochondrion is a semiindependent organelle as it possesses its own DNA and is capable of producing its own proteins on its own ribosomes, which are referred to as mitoribosomes. 

NO has a cytostatic effect by inhibiting ATP synthesis [99] via Kreb s cycle (aconitase inhibition, [100]), glycolysis (GADPH inhibition) and mitochondrial respiration (NAD ubiquinone oxydoreductase and succinate ubiquinone oxydoreductase inhibitions, [101]). Another pathway is the ornithine decarboxylase inhibition. This enzyme is implicated in polyamine production necessary to cell proliferation and its activity is inhibited by NO in human colon cancer cells HT-29 and Caco-2 [102]. Furthermore NO directly inactivates ribonucleotide reductase [103] of TA3 cancer cells (murine breast cancer cells) [104]. This enzyme controlling DNA synthesis catalyses desoxyribonucleotides synthesis, and its inhibition blocks cells in S phase. This inhibition is rapid and reversible in K562 and TA3 cells [105]. 

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