Patient pyruvic acid

Lactic acidosis is one of the most common canses of high SAG metabolic acidosis. Lactic acid is the end prodnct of anaerobic metabolism of glucose (glycolysis). In normal individnals, lactic acid derived from pyruvate enters the circulation in small amonnts and is promptly removed by the liver. In the liver, and to a lesser extent in the kidney, lactic acid is reoxidized to pyruvic acid, which is then metabolized to CO2 and H2O. The normal plasma lactate concentration in healthy subjects is approximately 1 rnEq/L. " The diagnosis of lactic acidosis should be considered in aU patients with metabolic acidosis... 

Other Organic Acids. Pyruvic acid, the clearance of which is also reduced during renal failure (Z4), has been found to be slightly increased in the blood of a few patients with chronic renal diseases (B18). 

A4. Amatuzio, D. S., and Nesbitt, S., A study of pyruvic acid in the blood and spinal fluid of patients with liver disease with and without hepatic coma. J. Clin. Invest. 29, 1486 (1950). 

Fig. 3.22. GC separation of keto and hydroxy acids from the urine of a patient with maple syrup urine disease. Top chromatogram, the patient before dietary treatment middle chromatogram, the same patient after two days on a diet bottom chromatogram, a mixture of reference compounds. Peaks 1, lactic acid 2, 2-hydroxyisobutyric acid 3, 2-hydroxybutyric acid 4, pyruvic acid 5, 3-hydroxyisobutyric acid 6, 3-hydroxybutyric acid 7, 2-hydroxyisovaleric acid 8, 2-ketobutyric acid 9, malonic acid (internal standard) 10, 2-methyl-3-hydroxybutyric acid 11, 2-hydroxy-n-valeric acid 12. methylmalonic acid 13, 3-hydroxyisovaleric acid 14a and b, 2-ketoisovaleric acid IS, acetoacetic add 16, 2-hydroxyisocaproic acid 17, 2-hydroxy-3-methylvaleric acid 18a, L-2-keto-3-methylvaleric add 18b, D-2-keto-3-methyl-valeric acid 19, 2-ketoisocaproic acid. Reproduced from [386],...

Histidinemia is a rare hereditary disease characterized by high levels of histidine in blood and urine [92-94]. Affected patients often have speech deficiencies, and excessive amounts of imidazole pyruvic acid are found in the urine. 

The histidinemic urine is sometimes only weakly positive or negative on ferric chloride testing, which reflects either the instability of imidazole-pyruvic acid, the relation of its excretion to protein intake, immaturity of histidine transaminase, or a combination of these factors. Even after histidine loading, histidinemic neonates excrete much smaller quantities of imi-dazolepyruvic acid than do older children. In patients with urocanase deficiency, the levels of blood histidine and urine imidazolepyruvic acid are normal or slightly elevated. Therefore, it is necessary to do a quantitative analysis of blood histidine and urine ferric chloride test in order to overlook the patients with this condition. 

Gross and associates found an increased loss of fat in the stools in patients with cirrhosis and postulated defective formation of bile salts as the cause. Serum concentrations of sodium, potassium, calcium, and phosphorus have been found to be lower than normal, and blood pyruvic acid levels elevated, in patients with decompensated alcoholic cirrhosis. When an adequate diet was instituted, these findings reverted to normal. The low levels of calcium and phosphorus may have resulted from an increase... 

At autopsy, multiple areas of necrosis are found in the grey matter of the central part of the brain and in the spinal cord [141]. Leigh compared these changes to Wernicke s encephalopathy, though with a different distribution. This suggested either thiamine deficiency or inability to utilize thiamine normally, but treatment with thiamine or thiamine pyrophosphate has no effect on the course of the disease [142]. Lipoic acid, like thiamine pyrophosphate involved in the oxidative decarboxylation of pyruvic acid, has been given to some patients [137] the concentration of pyruvic acid in the blood fell and clinical improvement was claimed. Others have tried lipoic acid treatment with less success—the pyruvic acid content of the blood fell, but there was no effect on the clinical course of the disease [136]. It is now known that the enzymes dec2irboxylating pyruvic acid are normal and that the metabolic error results from a lack of pyruvate carboxylase. 

Inherited aldolase A deficiency and pyruvate kinase deficiency in erythrocytes cause hemolytic anemia. The exercise capacity of patients with muscle phos-phofiaictokinase deficiency is low, particularly on high-carbohydrate diets. By providing an alternative lipid fuel, eg, during starvation, when blood free fatty acids and ketone bodies are increased, work capacity is improved. 

Schweizer, O., Howland, W. S., Sullivan, C., and Vertes, E., The effect of ether and halothane on blood levels of glucose, pyruvate, lactate and metabolites of the tricarboxylic acid cycle in normotensive patients during operation. Anes-thesiology 28, 814-822 (1967). 

Patients also suffer from lactic acidosis because the excess pyruvate that accumulates is converted to lactic acid. 

Biotin (vitamin B ) is widespread in foods and is also synthesized by intestinal bacteria. It is a coenzyme for the carboxylation of pyruvate, acetyl-coenzyme-A (CoA), propionyl CoA, and /1-methyl-crotonyl CoA and is involved in fatty acid formation and in energy release from carbohydrates. In humans deficiencies only occur in patients with an abnormal gut flora and manifests itself as exfoliative dermatitis and alopecia. 

The three compounds, acetoacetate, acetone, and 3-hydroxybutyrate, are known as ketone bodies.60b The inability of the animal body to form the glucose precursors, pyruvate or oxaloacetate, from acetyl units sometimes causes severe metabolic problems. The condition known as ketosis, in which excessive amounts of ketone bodies are present in the blood, develops when too much acetyl-CoA is produced and its combustion in the critic acid cycle is slow. Ketosis often develops in patients with Type I diabetes mellitus (Box 17-G), in anyone with high fevers, and during starvation. Ketosis is dangerous, if severe, because formation of ketone bodies produces hydrogen ions (Eq. 17-5) and acidifies the blood. Thousands of young persons with insulin-dependent diabetes die annually from ketoacidosis. 

Deficiency of pyruvate dehydrogenase is the most frequent cause of lactic acidemia ac Since this enzyme has several components (Fig. 15-15), a number of forms of the disease have been observed. Patients are benefitted somewhat by a high-fat, low-carbohydrate diet. Transient lactic acidemia may result from infections or from heart failure. One treatment is to administer dichloroacetate, which stimulates increased activity of pyruvate dehydrogenase, while action is also taken to correct the underlying illness.d Another problem arises if a lactate transporter is defective so that lactic acid accumulates in muscles.6... 

An individual has been found who is missing malic enzyme in his cytoplasm. He has instead an enzyme that converts the oxalacetate made from the citrate lyase reaction directly to pyruvate and C02. Discuss this patient in terms of the likely effect of these changes on his ability to synthesize fatty acids. 

Several inherited disorders are associated with faulty operation of the electron transport pathway. ATP production is diminished in such cases. These disorders are known as mitochondrial myopathies, and they are associated with the absence of specific polypeptide chains found in complexes I, III, or IV. In many cases, the problem may be traced to specific lesions in mitochondrial DNA, which codes for at least 13 polypeptide chains found in these complexes. Myopathies are tissue specific some affect the heart, others the skeletal muscle. Many are accompanied by lactic acidosis, because the inability to reduce NADH normally results in its accumulation and the channeling of pyruvate toward lactic acid production. In complex I disorders, the oxidation of FADH2 is not impeded. In complex III lesions, neither NADH nor FADH2 can be oxidized. However, use has been made by B. Chance and colleagues of menadione (Chapter 6) and ascorbic acid in such cases. The former can oxidize UQH2, whereas ascorbate can oxidize menadione and reduce cytochrome c. Marked clinical improvement in affected patients follows such treatment. 

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