Metabolism in glycolysis

Hypothyroidism may also impair substrate utifization. Hypothyroidism decreased the insulin-regulated rates of glucose uptake into muscle fibers, and glucose utilization within the muscle fiber to synthesize glycogen or metabolize in glycolysis (Dimitriadis et ai, 2006 Dubaniewicz et al, 1989). Furthermore, mitochondrial function is impaired in hypothyroid muscles, manifested by a decrease in the maximal mitochondrial respiratory rate (ZoU et al, 2001), reduced O2 consumption (Crespo-Armas et al, 1992) and reduced muscle oxidative capacity (Baldwin etal, 1980 Dudley et al, 1987 McAllister 1991). 

The rate at which Cl of glucose, as compared with C6, is converted to CO2 is used as an index for the quantitative importance of different pathways of carbohydrate metabolism. In Glycolysis (see). Cl and C6 become equilibrated at the level of the triose phosphates. Subsequent oxidation and decarboxylation in the tricarboxylic acid cycle therefore results in equal rates of production of COj from [l- C]glu-cose and [6- C]gjucose. 

Zw, glucoso-6-phosphate will be mainly metabolized in glycolysis. This, in turn, will lead to the anaerobic biosynthesis of pentoses from glycolytic metabolites with the participation of transaldolase and transketolase enzymes. It is also possible that the lethal effect on the Pgd" mutation is aggravated because the accumulation of 6-phosphogluconate is inhibitory to the first steps of glycolysis. Similar data were obtained by Hughes and Lucchesi (1977). 

In spite of the number of different structural types lipids share a common biosyn thetic origin m that they are ultimately derived from glucose During one stage of car bohydrate metabolism called glycolysis glucose is converted to lactic acid Pyruvic acid IS an intermediate... 

The importance of phosphates in intermediary metabolism became evident with the discovery of the role of ATP, adenosine diphosphate (ADP), and inorganic phosphate (Pj) in glycolysis (Chapter 17). 

Generally, NAD-linked dehydrogenases catalyze ox-idoreduction reactions in the oxidative pathways of metabolism, particularly in glycolysis, in the citric acid cycle, and in the respiratory chain of mitochondria. NADP-linked dehydrogenases are found characteristically in reductive syntheses, as in the extramitochon-drial pathway of fatty acid synthesis and steroid synthesis—and also in the pentose phosphate pathway. 

Glucose 6-phosphate is an important compound at the junction of several metabolic pathways (glycolysis, gluconeogenesis, the pentose phosphate pathway, glycogenosis, and glycogenolysis). In glycolysis, it is converted to fructose 6-phosphate by phosphohexose-isomerase, which involves an aldose-ketose isomerization. 

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-... 

During the recovery period from exercise, ATP (newly produced by way of oxidative phosphorylation) is needed to replace the creatine phosphate reserves — a process that may be completed within a few minutes. Next, the lactic acid produced during glycolysis must be metabolized. In the muscle, lactic acid is converted into pyruvic acid, some of which is then used as a substrate in the oxidative phosphorylation pathway to produce ATP. The remainder of the pyruvic acid is converted into glucose in the liver that is then stored in the form of glycogen in the liver and skeletal muscles. These later metabolic processes require several hours for completion. 

Nevertheless, using GC-based technologies, the quantification of several important intermediates of central metabolism, especially phosphorylated intermediates, is not very reliable, presumably because these compounds and their derivatives are not thermostable. For an analysis of these groups of metabolites, an LC-MS (liquid chromatography or HPLC coupled to MS) is more suitable, because it eliminates the need for volatility and thermostability and thereby eliminates the need for derivatization. Using a triple quadrupole MS, most of the intermediates in glycolysis, in the pentose phosphate pathway, and in the tricarboxylic acid cycle were measured in E. coli [214]. 

Identification of the energy source for muscle contraction and determination of the order in which the phosphate esters were metabolized was helped by the use of inhibitors. These inhibitors blocked different stages in glycolysis and caused preceding substrates to accumulate in quantities which could greatly exceed those normally present. The compounds were then isolated, identified, and used as specific substrates to identify the enzymes involved in their metabolism. Iodoacetic acid (IAc) was one of the most important inhibitors used to analyze glycolysis. 

Glycolysis is the major route of carbohydrate metabolism in all cell types and the TCA is a focal point allowing the integration of carbohydrate, amino acid and lipid metabolism. The two pathways are illustrated in Figures 3.9 and 3.14. These two well-known pathways exemplify many of the general principles of metabolic regulation described above. 

The three control steps in glycolysis are reactions catalysed by HK, PFK-1 and PK. All three reactions involve ADP/ATP cycling and are strongly exergonic suggesting they operate far from the true equilibrium position. Such reactions are physiologically difficult to reverse and so act as metabolic one-way streets . 

Marine organisms concentrate metals in their tissues and skeletal materials. Many of these trace metals are classified as micronutrients because they are required, albeit in small amounts, for essential metabolic functions. Some are listed in Table 11.4, illustrating the role of metals in the enzyme systems involved in glycolysis, the tricarboxylic acid cycle, the electron-transport chain, photosynthesis, and protein metabolism. These micronutrients are also referred to as essential metals and, as discussed later, have the potential to be biolimiting. 

---