Gluconeogenesis precursors

See also Amino Acids, Proteins, Gluconeogenesis Precursors, Essential Amino Acids... 

See also F, Glycerol Kinase, Glycolysis, Gluconeogenesis, Glycerol Metabolism, Gluconeogenesis Precursors, Figure 12.2... 

See also Anaerobic Glycolysis, Lactate Fermentation, Glycolysis, NADH, NAD+, Gluconeogenesis Precursors... 

Lactate - the most significant gluconeogenesis precursor. Lactate is produced when insufficient oxygen is present to maintain aerobic glycolysis. Lactate in exercising muscle is released into the blood where it travels to the liver for participation in gluconeogenesis. 

See also Gluconeogenesis Precursors, Gluconeogenesis Substrates, Gluconeogenesis Enzymes, Regulation of Gluconeogenesis... 

Gluconeogenesis Formation of glucose from precursors other than carbohydrates (especially by the liver and kidney) using amino acids from proteins, glycerol from fats, or lactate produced by muscle during anaerobic glycolysis. 

Gluconeogenesis is the de novo synthesis of glucose from none carbohydrate sources. These sources (precursors) are lactic acid, glycerol and the amino acids, especially alanine, glntamine and aspartic acid (Fignre 6.22). 

Figure 6.22 Major precursors for gluconeogenesis. FBP is fructose 1,6-bisphosphate.

In this book it is suggested that one possible cause of death in prolonged starvation is severe hypoglycaemia. This may be due to a lack of amino acid precursors since almost all the body protein has been broken down. Alternatively, the fat store in the body has been totally depleted, so that the plasma fatty acid level will be close to zero. Consequently, there will be no fatty acid oxidation in the liver and therefore little or no ATP generation to support gluconeogenesis. Post-mortem studies on individuals who have died of starvation show that the fat stores are totally depleted. This topic is discussed further in Chapter 16. 

Hormones can modify the concentration of precursors, particularly the lipolytic hormones (growth hormone, glucagon, adrenaline) and cortisol. The lipolytic hormones stimulate lipolysis in adipose tissue so that they increase glycerol release and the glycerol is then available for gluconeogenesis. Cortisol increases protein degradation in muscle, which increases the release of amino acids (especially glutamine and alanine) from muscle (Chapter 18). 

Gluconeogenesis. The gluconeogenic pathway is present in the kidney, as in the liver. Thus, amino acids (and lactate) can be converted to glucose in the kidney but a major precursor, in acidotic conditions, is glutamine. 

The amino acid precursors for gluconeogenesis are provided from the degradation of muscle protein. 

Lactate as a precursor for gluconeogenesis is mainly derived from muscle (see Cori cycle, p. 338) and erythrocytes. LDH (see p. 98) oxidizes lactate to pyruvate, with NADH+H" formation. 

Glucocorticoids—mainly cortisol (see p. 374)—induce all of the key enzymes involved in gluconeogenesis [4, 6, 8, 9]. At the same time, they also induce enzymes involved in amino acid degradation and thereby provide precursors for gluconeogenesis. Regulation of the expression of PEP carbo>Q -kinase, a key enzyme in gluconeogenesis, is discussed in detail on p. 244. 

With two exceptions (lysine and leucine see below), all of the proteinogenic amino acids are also glucogenic. Quantitatively, they represent the most important precursors for gluconeogenesis. At the same time, they also have an anaplerotic effect—1. e., they replenish the tricarboxylic acid cycle in order to feed the anabolic reactions that originate in it (see p. 138). 

The main precursors of gluconeogenesis in the liver are lactate from anaerobically working muscle cells and from erythrocytes, glucogenic amino acids from the digestive tract and muscles (mainly alanine), and glycerol from adipose tissue. The kidney mainly uses amino acids for gluconeogenesis (Glu, Gin see p.328). 

There is also a corresponding circulation system for the amino acid alanine. The alanine cycle in the liver not only provides alanine as a precursor for gluconeogenesis, but also transports to the liver the amino nitrogen arising in muscles during protein degradation. In the liver, it is incorporated into urea for excretion. 

Gortisol promotes net protein breakdown in skeletal muscle to provide amino acids as precursors for gluconeogenesis and ketone body synthesis (keto-genesis). 

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