Pyruvate ratio

Similarly, monitoring the amount of mtDNA, usually via the mtDNA nuDNA ratio [72], provides a more sensitive index of diminishing mitochondrial biomass and much of this work focuses on peripheral blood samples because they are readily available. In fibroblasts treated with ddC for 4 weeks, mtDNA dropped by 80% within the first week and the lactate/pymvate ratio lagged behind, but was pathologically elevated after 3 weeks. A 4-week wash-out treatment then showed that mtDNA returned to 90% of the initial value within 3 weeks and lactate/pyruvate ratio gradually normalized over 4 weeks. It bears reiteration in this context that... 

Table 1.4.6 Reference values for blood lactate, pyruvate, ACAC and according to age, fed state and fasting state. L P lactate-.pyruvate ratio...

Metabolically, acetyl CoA that is generated is diverted to ketogenesis, and urea cycle activity is decreased, leading to hyperammonaemia associated with fasting hypoglycaemia, increased lactataemia associated with an increased lactate pyruvate ratio, and increased ketonaemia with ratio < 1. Data from a patient affected with a PC defect are presented in Table 1.4.12. 

Data from a patient affected with a PDH defect are presented in Table 1.4.13. In general, hyperlactataemia (increasing with meals) associated with a normal lactate pyruvate ratio and normal ketonaemia is observed. The ketogenic diet is a rational treatment for PDH complex deficiency. 

Fig. 1.4.5 Effects of blood storage temperature and delay between sample preparation and measurement on the lactate pyruvate ratio...

From these data Krebs and Veech concluded that the oxidation state of the NAD system is determined largely by the phosphorylation state ratio of the adenylate system.169 If the ATP level is high the equilibrium in Eq. 17-42a will be reached at a higher [NAD+]/[NADH] ratio and lactate may be oxidized to pyruvate to adjust the [lactate]/[pyruvate] ratio. 

Calculated from the lactate/pyruvate ratio, assuming NAD and NADH at equilibrium, and using an equilibrium constant of 1.11 X 10-4. [From R. L. Veech, L. V. Eggleston, and H. A. Krebs, Biochem. 7.115, 609(1969).]... 

On physical examination, the patient was slightly febrile (38.4°C). Serum concentrations of lactate (24.6 mg/dL) and pyruvate (3.8 mg/ dL) were elevated (normal values are 5-18 mg/ dL and 0.55-1.0 mg/dL, respectively). Her lac-tate pyruvate ratio was elevated as well (34 1 normal range 10 1 to 20 1). Analysis of lumbar... 

If the history, physical findings, and laboratory results are suggestive but not conclusive of a particular mitochondrial disease (e.g., MELAS), then a second tier of tests is performed. These include blood and CSF lactate and pyruvate, as well as the lactate/pyruvate ratio timed or random measurement of amino acids in blood, urine, and CSF organic acids in urine and CSF and ketones and free and total carnitine in blood and urine. 

Metabolism Global metabolic profile via metabolomics (e.g. NMR spectroscopy, liquid chromatography-mass spectrometry (LC-MS), Lactate/pyruvate ratio, glucose and amino acid consumption, succinate dehydrogenase levels... 

Glucose utilization, O2 consumption, growth inhibition, lactate/pyruvate ratios, glutathione/redox status Arachidonic acid cascade H-AA release, PGE2 release, leukotrienes and HETEs) cytokine release (IL-1 3, TNFa)... 

Chariot P, Monnet I, Mouchet M, Rohr M, Lefaucheur JP, Dubreuil-Lemaire ML, et al. Determination of the blood lactate pyruvate ratio as a non-invasive test for the diagnosis of zidovudine myopathy. Arthritis Rheum 1994 37 583-6. 

Under normal conditions, lactate is metabolized in the liver and the blood lactate level is between 1 and 2 mM. Lactate accumulation in body fluids can be due to increased production and/or decreased utilization. Blood lactate-to-pyruvate ratio below 25 suggests defects in a gluconeogenic enzyme (Chapter 15) or pyruvate dehydrogenase (discussed later). A common cause of lactic acidosis is tissue hypoxia caused by shock, cardiopulmonary arrest, and hypoperfusion. Inadequate blood flow leads to deprivation of oxygen and other nutrients to the tissue cells as well as to the removal of waste products. Oxygen deprivation leads to decreased ATP production and accumulation of NADH, which promotes conversion of pyruvate to lactate. 

With a constant of K = 2.7640-5 mol/1 (pH 7.0, 25°C) the equilibrium of the LDH-catalyzed reaction lies far to the lactate side. This means that whereas for lactate sensors based on LDH the forward reaction has to be forced by alkaline buffer and pyruvate- or NADH-trapping agents, the reduction of pyruvate proceeds spontaneously under normal conditions. This direction of the reaction has been used in a sequence electrode for pyruvate assay (Weigelt et al., 1987b). In the presence of lactate monooxygenase (LMO) lactate formed from pyruvate by LDH is oxidized by molecular oxygen, the consumption of which was indicated at a Clark-type electrode. The enzymes were immobilized in a gelatin membrane. Of course such a sensor measures the concentration of lactate in the sample, too. Therefore it is suited to the determination of the lactate/pyruvate ratio, which is a clinically important parameter. Pro-... 

When—under comparable conditions—the arterial oxygen tension was lowered to such an extent that values of oxygen tension below 30 mm Hg occurred in the cerebral venous blood, a decrease in arterial blood flow and in oxygen uptake was registered, whereas the glucose uptake of the cerebral tissue and the lactate-pyruvate ratio of cerebral venous blood continued to increase. In these experiments the return to initial... 

Figure 2. Effect of progressively decreasing arterial oxygen tension on cerebral blood flow, oxygen and glucose uptake of the brain tissue, and lactate pyruvate ratio of cerebral venous blood under conditions of nonrespiratory...

Under the conditions of cerebral edema and nonrespiratory acidosis, the cerebral blood flow rate did not increase as soon as the oxygen tension in cerebral venous blood decreased below the reaction threshold. During edema, a decrease of oxygen tension below the threshold value led to a slight decrease in cerebral blood flow and cerebral oxygen uptake however, glucose uptake of the cerebral tissue and the lactate-pyruvate ratio of the cerebral venous blood increased. When arterial oxygen tensions were returned to normal, the cerebral blood flow and the cerebral... 

V y of pyruvate, fatty acids, and other fuels. In many cases, the inhibition of mitochondrial electron transport results in higher than normal levels of lactate and pyruvate in the blood and an increased lactate/pyruvate ratio. NADH oxidation requires the completed transfer of electrons from NADH to O2, and a defect anywhere along the chain will result in the accumulation of NADH and decrease of NAD+. The increase in NADH/NAD inhibits pyruvate dehydrogenase and causes the accumulation of pyruvate. It also increases the conversion of pyruvate to lactate, and elevated levels of lactate appear in the blood. A large number of genetic defects of the proteins in respiratory chain complexes have, therefore, been classified together as "congenital lactic acidosis."... 

Lactate and pyruvate are in equilibrium in the cell, and the ratio of lactate to pyruvate reflects the NADH/NAD + ratio. Both acids are released into blood, and the normal ratio of lactate to pyruvate in blood is approximately 25 1. This ratio can provide a useful clinical diagnostic tool. Because lactic acidemia can be the result of a number of problems, such as hypoxia, MERFF, thiamine deficiency, and pyruvate dehdyrogenase deficiency, under which of these conditions would you expect the lactate/pyruvate ratio in blood to be much greater than normal ... 

The measurement of the lactate/pyruvate ratio in plasma is possible by using a lactate dehydrogenase-lactate monooxygenase sequence electrode [373]. The sensor is equally sensitive to lactate and pyruvate (Figure 14-34), because of the high enzyme loading and the... 

Significantly higher levels of brain lactate and pyruvate concentrations and increased lactate to pyruvate ratios accompany hypocapnic hypoxia (Beck and Krieglstein,... 

Acylcamitine profiles indicate elevated long-chain acylcamitines C12, C14, C18, and C18 l, but they also show elevated 3-hydroxyacylcamitines hydroxy-C14, hydroxy-C16, and hydroxy-C 18 1. Urine organic acid analysis shows dicarboxylic acids and 3-hydroxydicarboxylic acids. These latter metabolites can rarely also be observed in certain patients with respiratory chain enzyme deficiencies. Lactate and the lactate to pyruvate ratio are often elevated. The incidence of TCHAD deficiency on newborn screening is estimated at 1 60,000. The diagnosis is usually confirmed by mutation analysis of the genes for the a-chain HADHA and the p-chain HADHB. Enzyme assays are nowadays rarely available. 

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