Glucose intermediary metabolism

The introduction of the invertase from yeast alone was not sufficient. Invertase cleaves sucrose to release the two component sugars, glucose and fructose. While fructose can be readily metabolized by fructokinase in potato tubers, there is insufficient hexokinase activity in developing potato tubers to bring the glucose into intermediary metabolism. Therefore, it was necessary to introduce a second transgene, a bacterial glucokinase, in order to ensure that the hexoses became available for subsequent metabolism.25... 

As with all the major transmitters, acetylcholine is stored in vesicles within the nerve terminal from which it is released by a calcium-dependent mechanism following the passage of a nerve impulse. The inter-relationship between the intermediary metabolism of glucose, phospholipids and the uptake of choline is summarized in Figure 2.14. 

Figure 2.14 Iriter-relationship between intermediary. metabolism of glucose, phospholipids and acetylcholine synthesis. Acetyl CoA acetyl coenzyme A CAT-catechol-O-methyltransferase AChE acetylcholinesterase.

Catecholamines exert a pronounced effect on intermediary metabolism. An activation of /8-adrenoceptors leads to lipolysis and glycogenolysis resulting in increased plasma glucose and free fatty... 

Their relative blood concentrations are an expression of nutritional balance, providing a view of the metabolic disturbances arising in a patient. In conjunction with the measurement of unesterified fatty acids (UEFA) and glucose, they are useful tools with which to investigate intermediary metabolism in health and disease, particularly in inherited metabolic diseases. 

For fructose to enter the pathways of intermediary metabolism, it must first be phosphorylated (Figure 12.2). This can be accomplished by either hexokinase or fructokinase (also called ketohexo-kinase). Hexokinase phosphorylates glucose in all cells of the body (see p. 96), and several additional hexoses can serve as substrates for this enzyme. However, it has a low affinity (that is, a high Km, see p. 59) for fructose. Therefore, unless the intracellular concentration of fructose becomes unusually high, the normal presence of saturating concentrations of glucose means that little fructose is converted... 

An expanded section, Intermediary Metabolism, constitutes the third part of the book. Disorders of glucose and fatty acid metabolism are discussed in the chapters Glucose 6-Phosphate... 

Anesthetized rats are used for testing the side effect potential of a candidate compound on intermediary metabolism in liver, muscle and adipose tissue with subsequent effects on metabolic blood parameters (e.g. glucose, lactate, free fatty acids, triglycerides) and insulin. The use of anesthetized rats represents more a principal assessment of the pharmacological side effect potential since the candidate compound must be administered intravenously or intraperitoneally (enteral/intestinal administration should be avoided due to the anesthesia-induced decrease in intestinal motility with subsequent impairment of enteral absorption), compared to the study in conscious rats in which the candidate compound can be studied after oral administration, which in most cases represents the clinical route of administration for small molecular drugs. 

Conscious rats are used for testing the side effect potential of a candidate compound on intermediary metabolism in liver, muscle and adipose tissue with subsequent effects on metabolic blood parameters (e.g. glucose, lactate, free fatty acids, triglycerides) and insulin after oral administration, which represents in most cases the clinical route of administration for small molecular drugs. 

At the end of such multiple dose studies the animals are killed in terminal anesthesia and maximal blood collection is possible. Therefore, not only the target metabolic parameters (e.g. glucose, lactate, free fatty acids, triglycerides, cholesterol) but also other parameters, which reflect intermediary metabolism (e.g. keton bodies, urea, uric acid) as well as safety parameters (e.g. ASAT, ALAT, AP, LDH) can be determined by clinical chemistry. 

Hexoses play a central role in the carbohydrate metabolism in a large number of organisms. O Scheme 1 provides a basic summary allowing one to understand the central position of hexoses, and D-glucose in particular, in the intermediary metabolism. 

Some steps in the intermediary metabolism of glycogen and hexoses are shown in Figure 25-9. Each step is enzymatically catalyzed. In some cases, different enzymes are responsible for the forward and reverse reactions. For example, the initial phosphorylation of glucose is mediated by glucokinase, but the reverse reaction depends on glucose-6-phosphatase. 

Various inborn errors of metabolism (Table 25-1) result from deficiencies or absence of some of the enzymes listed in Figure 25-9. Some of these are discussed later in the chapter. The relationship of carbohydrate metabolism to the production of lactate, ketone bodies, and triglycerides is also depicted in Figure 25-9. The pentose phosphate pathway, also known as the hexose monophosphate shunt, is an alternative pathway for glucose metaboUsm that generates the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH), which is used in maintaining the integrity of red blood cell membranes, in lipid and steroid biosynthesis, in hydroxylation reactions, and in other anabolic reactions. The complete picture of intermediary metabolism of carbohydrates is rather complex and interwoven with the metabolism of lipids and amino acids. For details, readers should consult a biochemistry textbook. 

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