Pyruvate blood concentration

Respiratory exchange measurements, namely, oxygen consumption ( 02) and the concentration of oxygen and carbon dioxide in expired gases, were monitored throughout rest, exercise, and recovery. Blood samples taken at the end of the rest, exercise, and recovery periods, were analyzed for glucose, lactate, and pyruvate. Blood samples were obtained during the exercise sessions only in study 2. 

PDH deficiency results in raised blood concentrations of pyruvate, lactate and alanine. Some patients respond to supplementation with lipoic acid or thiamin (coenzymes for PDH). Treatment with a low carbohydrate, ketogenic diet has been advocated but with limited success. (The ketone bodies readily cross the blood-brain barrier and their catabolism produces acetyl CoA independently of PDH.)... 

The lactate produced mainly in muscle diffuses in blood and reaches the heart where the principal function of LDH-H is oxidizing lactate to pyruvate, which can then be utilized through the Krebs cycle. In fact, if blood concentrations of lactate are increased, the uptake of that metabolite by the heart is also increased. Thus, the H-type is the true lactic dehydrogenase, while the M-type is really a pyruvic reductase. 

The decarboxylation and oxidation of pyruvate to form acetyl CoA requires the coenzyme thiamin diphosphate, which is formed from vitamin (section 11.6.2). In thiamin deficiency, this reaction is impaired, and deficient subjects are unable to metabolize glucose normally. Especially after a test dose of glucose or moderate exercise they develop high blood concentrations of pyruvate and lactate. In some cases this may be severe enough to result in life-threatening acidosis. 

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. 

Most patients with pyruvate-carboxylase deficiency present with failure to thrive, developmental delay, recurrent seizures and metabolic acidosis. Lactate, pyruvate, alanine, [3-hydroxybutyrate and acetoacetate concentrations are elevated in blood and urine. Hypoglycemia is not a consistent finding despite the fact that pyruvate carboxylase is the first rate-limiting step in gluconeogenesis. 

Muscle protein catabolism generates amino acids some of which may be oxidized within the muscle. Alanine released from muscle protein or which has been synthesized from pyruvate via transamination, passes into the blood stream and is delivered to the liver. Transamination in the liver converts alanine back into pyruvate which is in turn used to synthesise glucose the glucose is exported to tissues via the blood. This is the glucose-alanine cycle (Figure 7.11). In effect, muscle protein is sacrificed in order to maintain blood adequate glucose concentrations to sustain metabolism of red cells and the central nervous system. 

Marion D, Puccio A, Wisniewski S, Kochanek P, Dixon C, et al. 2002. Effect of hyperventilation on extracellular concentrations of glutamate, lactate, pyruvate, and local cerebral blood flow in patients with severe traumatic brain injury. Grit Care Med 30(12) 2619-2625. 

Lactate consumption The direction of the lactate dehydrogenase reaction depends on the relative intracellular concentrations of pyruvate and lactate, and on the ratio of NADH/NAD+ in the cell. For example, in liver and heart, the ratio of NADH/NAD+ is lower than in exercising muscle. These tissues oxidize lactate (obtained from the blood) to pyruvate. In the liver, pyruvate is either converted to glucose by gluconeogenesis or oxidized in the TCA cycle. Heart muscle exclusively oxidizes lactate to CO2 and H20 via the citric acid cycle. 

Pyruvate kinase catalyzes the third irreversible step in glycolysis. It is activated by fructose 1,6-bisphosphate. ATP and the amino acid alanine allosterically inhibit the enzyme so that glycolysis slows when supplies of ATP and biosynthetic precursors (indicated by the levels of Ala) are already sufficiently high. In addition, in a control similar to that for PFK (see above), when the blood glucose concentration is low, glucagon is released and stimulates phosphorylation of the enzyme via a cAMP cascade (see Topic J7). This covalent modification inhibits the enzyme so that glycolysis slows down in times of low blood glucose levels. 

Finally, in the third mammlian grouping (dog, horse, rabbit, seal, swine), the fetal Hb is not expressed. In these species, even without HbF, the 02 affinity of fetal blood is kept higher than that of the adult. This difference is achieved by means of low concentrations of RBC DPG in the fetus and by higher-than-usual concentrations of DPG in the RBCs of adults. In most of these species, this fetal-adult difference in RBC DPG concentration is due to an enhanced catalytic capacity of the terminal part of the glycolytic path (indexed by pyruvate kinase activity, for example), which increases DPG flux towards pyruvate and lactate (see Poyart et ah, 1992). 

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