Blood pyruvate

Til. Role of the Vitamin Thiamine People with beriberi, a disease caused by thiamine deficiency, have elevated levels of blood pyruvate and a-ketoglutarate, especially after consuming a meal rich in glucose. How are these effects related to a deficiency of thiamine ... 

Growth and food efficiency were decreased in a dose-related manner in rats given 5, 10, and 20 mg/kg/day DNOC for 90 days (Den Tonkelaar et al. 1983). Urinary ketones, an indicator of endogenous fat catabolism, were increased at doses of 2.5, 5, and 10 mg/kg/day DNOC, but not at 20 mg/kg/day DNOC. Blood glucose was increased at 10 and 20 mg/kg/day DNOC, while blood protein was decreased only at 20 mg/kg/day DNOC. Blood pyruvate was also decreased at all doses. The increased blood glucose and decreased blood pyruvate were indicative of an inhibitory action of DNOC on glycolysis. 

Although elevated levels of blood urea nitrogen and blood glucose, and decreased blood pyruvate indicate metabolic disturbances caused by DNOC (Den Tonkelaar et al. 1983 Spencer et al. 1948) (see Section 2.5.2), these effects are not unique to DNOC exposure (see Section 2.5.2). Therefore, it would be useful to identify an effects that may be uniquely and quantitatively associated with exposure to DNOC. 

Fasting venous blood, drawn with a patient at rest, has a pyruvate concentration of 0.03 to O.lOmmol/L (0.3 to 0.9mg/dL). Arterial blood contains 0.02 to 0.08mmol/L (0.2 to 0,7mg/dL). Values for CSF are 0.06 to 0.19mmol/L (0,5 to 1.7mg/dL), Age-related reference intervals in CSF have been estabfished in children. Urine output of pyruvate is normally Immol/day or less. There are few clinical indications for measurement of blood pyruvate concentrations. 

Many factors aflFecting the pyruvate level in blood and urine, especially muscular exercise, have been studied they have been reviewed previously (A2, L15, M24, P4, S21, T8). Among the newer studies concerning the effect of hormones on blood pyruvate, we shall only mention that the blood level of pyruvic acid is increased after administration of adrenal steroids, which seem to have an inhibitory effect on the utilization of pyruvate (H18). 

Blood pyruvate concentration is not altered in most cases of diabetes mellitus (A5, D14, S28). Previous results, obtained by use of the colorimetric technique of Friedemann and Haugen (F12) and showing an apparent high pyruvate level during diabetic coma, are erroneous and are due to the interference of acetoacetic acid on pyruvic add determination with that technique (Lll, L12, L13). 

Defective utilization of pyruvate has, however, been shown by pyruvate tolerance tests during diabetes mellitus, the abnormality not being related to coincidental factors, such as age, sex, diet, or obesity (M30). Such defective utilization of pyruvate is also shown by abnormalities in blood pyruvate following glucose administration (A5, B34, M31). 

The increase of blood pyruvate following insulin administration is, however, comparable to that found in normal subjects (A5). 

The data summarized before, showing the coexistence of usually normal blood pyruvate and a-ketoglutarate levels with a probable decrease of blood citrate and inconstant abnormahties in the response of blood pyruvate and citrate to glucose and pyruvate administration, do not as yet allow a firm statement as to whether or not there exists a definite disturbance in one or more reactions of the tricarboxylic acid cycle during diabetes mellitus. 

Thus, De Schepper (D14) found an increase in blood pyruvate in acute viral hepatitis and in different varieties of hepatic cirrhosis the highest values were obtained during hepatic coma, whereas no elevation in blood pyruvate was observed in eases of jaundice due to extrahepatic obstruction. Other authors (A4, G17) found normal values in well-compensated cirrhosis. 

The alterations of blood pyruvate levels are of limited value in assessing liver dysfunction, since they are not of regular occurrence, are nonspecific (PI), and do not always follow the clinical symptoms (S38). 

A5. Amatuzio, D. S., Schrifter, N., Stutzman, F. L., and Nesbitt, S., Blood pyruvic acid response to intravenous administered glucose or insulin in the normal and in patients with liver disease and with diabetes mellitus. J. Clin. Invest. 31, 751 (1952). 

B16. Bianchessi, M., Estimation of blood pyruvic acid in liver diseases and in pancreatic diabetes. CUn. Chim. Acta 3, 179 (1958). 

D5. Dawson, A. M., de Croote, J., Rosenthal, W. S., and Sherlock, S., Blood pyruvic acid and alpha-ketoglutaric acid levels in liver disease and hepatic coma. Lancet i, 392 (1957). 

Elevated blood pyruvate and lactate, elevated blood alanine... 

The most logical explanation for the increase in blood pyruvic acid is that the increase results from the blocking of pyruvic decarboxylase. However, in experiments in which blood pyruvic acid levels in thiamine-deficient animals were correlated with the changes in the adrenals, it was concluded that the increase in blood pyruvate can be correlated more closely to adrenal hypertrophy than to thiamine deficiency. Furthermore, in thiamine-deficient adrenalec-tomized and hypophysectomized animals, pyruvemia was much less than in the controls. Finally, cortisone administration increases the level of blood pyruvate. Consequently, pyruvemia in thiamine-deficient animals may result from immediate stress caused by the deficiency and from progressive block of pyruvic decarboxylase due to the slow depletion of coenzyme. 

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... 

An intermediate in the catabolism of glucose. If there is inadequate oxygen available, it is converted to lactate (see lactate). If adequate oxygen is available, it is decarboxylated to acetyl-CoA, a reaction which requires, thiamine pyrophosphate as a cofactor. Increased blood pyruvate levels are therefore found in cases of thiamine deficiency. 

A test, used mainly for the diagnosis of thiamine deficiency, which consists of giving an oral load of glucose and measuring the subsequent blood pyruvate levels (see pyruvate). In normal individuals only a small rise in the level occurs. A larger increase, however, occurs in thiamine deficiency and in diseases where there is disturbed carbohydrate metabolism such as liver diseases. An absent response may be found in untreated diabetics. 

Beriberi is caused by a deficiency of thiamin (also called thiamine, aneurin(e), and vitamin Bj). Classic overt thiamin deficiency causes cardiovascular, cerebral, and peripheral neurological impairment and lactic acidosis. The disease emerged in epidemic proportions at the end of the nineteenth century in Asian and Southeast Asian countries. Its appearance coincided with the introduction of the roller mills that enabled white rice to be produced at a price that poor people could afford. Unfortunately, milled rice is particularly poor in thiamin thus, for people for whom food was almost entirely rice, there was a high risk of deficiency and mortality from beriberi. Outbreaks of acute cardiac beriberi still occur, but usually among people who live under restricted conditions. The major concern today is subclinical deficiencies in patients with trauma or among the elderly. There is also a particular form of clinical beriberi that occurs in patients who abuse alcohol, known as the Wer-nicke-Korsakoff syndrome. Subclinical deficiency may be revealed by reduced blood and urinary thiamin levels, elevated blood pyruvate/lactate concentrations and a-ketoglutarate activity, and decreased erythrocyte transketolase (ETKL) activity. Currently, the in vitro stimulation of ETKL activity by thiamin diphosphate (TDP) is the most useful functional test of thiamin status where an acute deficiency state may have occurred. The stimulation is measured as the TDP effect. 

Apart from some conflicting therapeutic cltiims there is, however, little if any, convincing evidence of an associated thiamine deficiency in this condition. Goodhart and Sinclair [28] found that the levels of cocarboxylase in the blood were normal in four out of the five patients studied by them, the fifth patient, in whom a low level was found, being also an alcohol addict. Martin [29] carried out pyruvate tolerance tests following the intravenous injection of pyruvate to a series of diabetic subjects and concluded that pyruvate metabolism was normal. Thompson, Butterfield and Kelsey-Fry [30] reported on the blood pyruvate levels in glucose-insulin tests performed on a series of diabetic patients with and without neuropathy, and found that the levels were no higher in patients with neuropathy than in the other diabetics. 

In the women with vitamin Bg deficiency, administration of this vitamin caused elevation of fasting blood-pyruvate levels, and reduction of plasma glucose, insulin, and blood-pyruvate responses after an oral glucose load. These changes were not found in the 28 non-vitamin Bg-deficient women. These results indicate that carbohydrate intolerance in women on oral contraceptives is... 

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