Gluconeogenic precursors

When amino acid carbons are the principal gluconeogenic precursors, the metabolic and physiological debts are particularly large compared to those incurred 

Gluconeogenic precursors include lactate, alanine, and several other amino acids, glycerol, and propionate (Chapter 22). 

Lactate, the end product of anaerobic glucose metabolism, is produced by most tissues of the body, particularly skin, muscle, erythrocytes, brain, and intestinal mucosa. In a normal adult, under basal conditions, these tissues produce 1,300 mM of lactate per day, and the normal serum lactate concentration is less than 1.2 mM/L. During vigorous exercise, the production of lactate can be increased several fold. Lactate is normally removed from the circulation by liver and kidney. Because of its great capacity to use lactate, liver plays an important role in the pathogenesis of lactic acidosis, which may be thought of as an imbalance between the relative rates of production and utilization of lactate (Chapter 39). 

Alanine, derived from muscle protein and also synthesized in the small intestine, is quantitatively the most important amino acid substrate for gluconeogenesis. It is converted to pyruvate by alanine aminotransferase (Chapter 17)  

Points of entry of amino acids into the pathway of gluconeogenesis. 

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Gluconeogenic precursors are molecules that can be used to produce a net synthesis of glucose. They include all the intermediates of glycolysis and the citric acid cycle. Glycerol, lactate, and the o-keto acids obtained form the deamination of glucogenic amino acids are the most important gluconeogenic precursors. 

The availability of gluconeogenic precursors, particularly gluco genic amino acids, significantly influences the rate of hepatic glu cose synthesis. Decreased levels of insulin favor mobilization of amino acids from muscle protein, and provide the carbon skele tons for gluconeogenesis. 

The glycerol backbone of the degraded triacylglycerol is carried by the blood to the liver, where it serves as an important gluconeogenic precursor. 

To review the curious behavior of the liver, and its handling of glucose when the liver synthesizes glycogen, it does So from gluconeogenic precursors. But when the liver oxidizes glucose, it tends to do so only to the point of pyruvate. 

A which neither liver glycogen nor gluconeogenic precursors (such as alanine and glycerol) can be... 

Glycerol is more reduced than the other gluconeogenic precursors, and it results primarily from triacylglycerol hydrolysis in adipose tissue. In liver and kidney, glycerol is converted to glycerol 3-phosphate by glycerol kinase ... 

Propionate is not a quantitatively significant gluconeogenic precursor in humans, but it is a major source of glucose in ruminants. It is derived from the catabolism of isolecucine, valine, methionine, and threonine from jd-oxidation of odd-chain fatty acids and from the degradation of the side chain of cholesterol. Propionate enters gluconeogenesis via the TCA cycle after conversion to succinyl-CoA (Chapter 18). 

As was previously mentioned, several metabolites are gluconeogenic precursors. Three of the most important substrates are described briefly. 

In liver and in other gluconeogenic tissues, the so-called L form of pyruvate kinase predominates, whereas the M form is found largely in muscle. The L form is inhibited both by ATP and by some amino acids, particularly alanine, the major gluconeogenic precursor among the amino acids. 

Figure 16.4 Outline of pathways for glucose synthesis from the major gluconeogenic precursors. 

Pymvate is produced in the hver from the gluconeogenic precursors lactate and alanine. Lactate dehydrogenase oxidizes lactate to pymvate, generating NADH (Fig. 31.4A), and alanine aminotransferase converts alanine to pyruvate (see Fig. 31.4B). 

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