Lactic acid cycle

Central to applying Warburg s theory is the suppression of cancer by the use of inhibitors that would break or inhibit the glucose-lactic acid cycle. The existing... 

The anticancer role of nitrogen-bearing compounds may be that of substances that inhibit or break, in one way or another, the enzyme-catalyzed reactions in the glucose-lactic acid cycle. The topic of enzyme inhibitors is in itself an expanding subspecialty within the field. Enzymatic reactions and enzyme-breaking actions are involved, for instance, in the efficacy of antibiotics and in other unexpected areas. 

Some glycogen is manufactured and stored in the muscles. However, glucose derived from this glycogen is available only for use by the muscle and not the general circulation. Lactic acid may leave the muscle and be reconverted to glucose in the liver and released into the blood. This process requires six ATPs for each glucose molecule, and is referred to as the lactic acid cycle or Cori cycle. A husband and wife team, Carl and Gerty Cori, describe it and they were jointly awarded the Nobel Prize in 1947. 

Lactic acid The normal concentration of lactate in the blood is about 1 mmol/L which is the balance between production and utilisation. Various tissues produce lactic acid and release it into the blood, from where it is taken up by liver and converted to glucose (or glycogen) (the Cori cycle, see above). 

Catalases catalyze the conversion of hydrogen peroxide to dioxygen and water. Two families of catalases are known, one having a heme cofactor and the second a structurally distinct family, found in thermophilic and lactic acid bacteria. The manganese enzymes contain a binuclear active site and the functional form of the enzyme cycles between the (Mn )2 and the (Mn )2 oxidation states. When isolated, the enzyme is in a mixture of oxidation states including the Mn /Mn superoxidized state and this form of the enzyme has been extensively studied using XAS, UV-visible, EPR, and ESEEM spectroscopies. Multifrequency EPR and microwave polarization studies of the (Mn )2 catalytically active enzyme from L. plantarum have also been reported. ... 

Pharmacoiogy The exact mechanism of action of colchicine in gout is not known. Colchicine apparently exerts its effect by reducing the inflammatory response to the deposited crystals and also by diminishing phagocytosis. Colchicine diminishes lactic acid production by leukocytes directly and by diminishing phagocytosis and thereby interrupts the cycle of urate crystal deposition and inflammatory response that sustains the acute attack. 

Some of the lactic acid formed in muscle and most of the lactate formed in less aerobic tissues (e.g., adipose tissue)1363 enters the bloodstream, which normally contains 1-2 mM lactate,136 and is carried to the liver where it is reoxidized to pyruvate. Part of the pyruvate is then oxidized via the citric acid cycle while a larger part is reconverted to glucose (Section J,5). 

This glucose may be released into the bloodstream and returned to the muscles. The overall process is known as the Con cycle. Lactic acid accumulates in muscle after vigorous exercise. It is exported to the liver slowly, but if mild exercise continues the lactate may be largely oxidized within muscle via the tricarboxylic acid cycle. Recent NMR studies have shown that lactic acid is formed rapidly during muscular contraction,... 

Now let us consider the further conversion of PEP and of the triose phosphates to glucose 1-phosphate, the key intermediate in biosynthesis of other sugars and polysaccharides. The conversion of PEP to glucose 1-P represents a reversal of part of the glycolysis sequence. It is convenient to discuss this along with gluconeogenesis, the reversal of the complete glycolysis sequence from lactic acid. This is an essential part of the Cori cycle (Section F) in our own bodies, and the same process may be used to convert pyruvate derived from deamination of alanine or serine (Chapter 24) into carbohydrates. 

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