Glycolysis lactate metabolism

Glycolysis the metabolic pathway leading from glucose to pyruvate and lactate. 

The ANLSH challenged the classic view [2, 3]. It postulates compartmentaliza-tion of brain lactate metabolism between neurons and astrocytes the activity-induced uptake of glucose takes place predominantly in astrocytes, which metabolize glucose anaerobically. Lactate produced from anaerobic glycolysis in astrocytes is then released from astrocytes and provides the primary metabolic fuel for neurons. The increased lactate in the neurons is converted to pyruvate via lactate dehydrogenase (LDH), which enters the TCA cycle, and increases ATP production in the neurons via oxidative phosphorylation (Fig. 8.1). This view is highly discussed, pro [4, 5]) and contra [1, 6]. 

This metabolic scheme, which is called lactate fermentation, is shown in Fig. 11-7. The coreactant cycle between the two dehydrogenase enzymes, glyceraldehyde-3-phosphate dehydrogenase (Step 6) and lactate dehydrogenase, ensures that there is regeneration of NAD+ in this particular oxidation state so that glycolysis, lactate fermentation, and the production of ATP can continue. 

Cardiovascular and septic shock, with resultant tissue hypoperfusion, are the most common causes of lactic acidosis. Poor tissue perfusion and hypoxia influence enzymatic pyruvate and lactate metabolism to stimulate anaerobic glycolysis and to decrease lactate utilization. This leads to hyperlactatemia and lactic acidosis. The mortality rate of this type of lactic acidosis may be as high as 80% and correlates with the degree of hyperlactatemia. 

Note that breakdown products of fat metabolism (glycerol, propionyl-CoA), protein degradation (alanine, other amino acids), and anaerobic glycolysis (lactate) are substrates for gluconeogenesis. Notably, the primary breakdown product of fat, acetyl-CoA, is not shown, because it cannot be effectively used by animals in gluconeogenesis. Some of the substrates are summarized as follows ... 

The process of glycolysis converts some, but not all, of the metabolic energy of the glucose molecule into ATP. The free energy change for the conversion of glucose to two molecules of lactate (the anaerobic route shown in Figure 19.1) is -183.6 kj/mol ... 

Glucose is metabolized to pyruvate by the pathway of glycolysis, which can occur anaerobically (in the absence of oxygen), when the end product is lactate. Aerobic tissues metabolize pyruvate to acetyl-CoA, which can enter the citric acid cycle for complete oxidation to CO2 and HjO, linked to the formation of ATP in the process of oxidative phosphorylation (Figure 16-2). Glucose is the major fuel of most tissues. 

Lactate is the end product of glycolysis under anaerobic conditions (eg, in exercising muscle) or when the metabolic machinery is absent for the further oxidation of pyruvate (eg, in erythrocytes). 

Brain Coordination of the nervous system Glycolysis, amino acid metabolism Glucose, amino acid, ketone bodies (in starvation) Polyunsaturated fatty acids in neonate Lactate ... 

Deficiencies of enzymes involved in glycolysis, the hexose monophosphate pathway, the closely related glutathione metabolism and synthesis, and nucleotide metabolism have emerged as causes of hereditary nonspherocytic hemolytic anemias (Table 1) (F10, Fll, M27). Some enzyme deficiencies, such as diphospho-glycerate mutase deficiency, lactate dehydrogenase deficiency, and NADH cy-... 

Under anaerobic conditions, various pathways exist for pyravate metabolism which serve to re-oxidize the reduced hydrogen carriers formed during glycolysis. The ultimate acceptor builds up as a waste product in the culture medium. The end-products of the pathways are (1) CO, ATP, and acetate (2) COj and ethanol (3) and CO2 (4) COj and 2,3-butylene glycol (5) COj, Hj, acetone, ATP, and butanol (6) succinate and (7) lactate. The pathway that occurs depends on the microorganism cultivated and the culture. 

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