Fundamentals of Human Nutrition/Glucose
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Written by: André Cunha
Metabolism is broadly deﬁned as the sum of biochemical processes in living organisms that either produce or consume energy (DeBerardinis, R.J et al. 2012). Core metabolism can be simpliﬁed to those pathways involving abundant nutrients like carbohydrates, fatty acids, and amino acids, essential for energy homeostasis and macromolecular synthesis in humans. Pathways of core metabolism can then be separated conveniently into three classes: those that synthesize simple molecules or polymerize them into more complex macromolecules (anabolism); those that degrade molecules to release energy (catabolism); and those that help to eliminate the toxic waste produced by the other classes (waste disposal). These pathways are profoundly important. Stated bluntly, they are the sole source of energy that allows life to resist the urge to degrade into entropy (DeBerardinis, R.J. 2012; Nelson, D & Cox, M. 2011).
Glucose occupies a central position in the metabolism of plants, animals and many microorganisms. It has relatively high potential energy and therefore it is a good fuel: the full oxidation of one molecule of glucose to carbon dioxide and water occurs in a range of standard free energy of - 2840 kJ/mol. By means of storage of glucose as a polymer of high molecular mass, such as starch and glycogen, the cell can store large quantities of hexose units while maintaining the cytosolic osmolarity relatively low. When the demand for energy increases, glucose can be converted from such intracellular storages into adenosine triphosphate (ATP) in an aerobic or anaerobic manner. (Nelson, D & Cox, M. 2011; Stryer, L. 2008).
Glucose is not only an excellent fuel, but it is also a precursor admirably versatile, able to meet a variety of metabolic intermediates in biosynthetic reactions (FIGURE 02). A bacterium like Escherichia coli can use the glucose as carbon skeletons for every amino acid, nucleotide, enzyme, fatty acid or other metabolic intermediate required for their growth (Nelson, D & Cox, M. 2011)
Glycolysis literally means "splitting sugars." In glycolysis, glucose (a six carbon sugar) is split into two molecules of a three-carbon sugar. Glycolysis yields two molecules of ATP (free energy containing molecule), two molecules of pyruvic acid and two "high energy" electron carrying molecules of NADH. Glycolysis can occur with or without oxygen. In the presence of oxygen, glycolysis is the first stage of cellular respiration. Without oxygen, glycolysis allows cells to make small amounts of ATP. This process is called fermentation.
Glycolysis (from glycose, an older term for glucose + -lysis degradation) is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+. The free energy released in this process is used to form the high-energy compounds ATP (adenosine triphosphate) and NADH (reduced nicotinamide adenine dinucleotide).
Glycolysis is a definite sequence of ten reactions involving ten intermediate compounds (one of the steps involves two intermediates). The intermediates provide entry points to glycolysis. For example, most monosaccharides, such as fructose, glucose, and galactose, can be converted to one of these intermediates. The intermediates may also be directly useful. For example, the intermediate dihydroxyacetone phosphate (DHAP) is a source of the glycerol that combines with fatty acids to form fat.
It occurs, with variations, in nearly all organisms, both aerobic and anaerobic. The wide occurrence of glycolysis indicates that it is one of the most ancient known metabolic pathways. It occurs in the cytosol of the cell.
The most common type of glycolysis is the Embden–Meyerhof–Parnas (EMP pathway), which was first discovered by Gustav Embden, Otto Meyerhof, and Jakub Karol Parnas. Glycolysis also refers to other pathways, such as the Entner–Doudoroff pathway and various heterofermentative and homofermentative pathways. However, the discussion here will be limited to the Embden–Meyerhof–Parnas pathway.
The entire glycolysis pathway can be separated into two phases (FIGURE 1):
The Preparatory Phase – in which ATP is consumed and is hence also known as the investment phase The PayOff Phase – in which ATP is produced.
In glycolysis, one molecule of glucose is degraded into a series of enzyme-catalyzed reactions, generating two molecules of the compound in three carbon atoms, pyruvate. During these sequential reactions part of glycolysis of glucose free energy is conserved as ATP and NADH (Nelson, D & Cox, M. 2011; Stryer, L. et al. 2008).
The glycolytic pathway (FIGURE 01) starts when glucose enters the cell through glucose transporters (GLUTs) and, once inside, it is phosphorylated to glucose-6-phosphate (G6P) by hexokinase 2 (HK2). Phosphoglucose isomerase catalyzes G6P to fructose-6-phosphate (F6P), which yields fructose-1,6-bisphosphate by phosphofructokinase 1 (PFK1), and then pyruvate and ATP by pyruvate kinase (PK) in the final step of glycolysis. Pyruvate is converted to acetyl-CoA, which enters the TCA cycle. Ultimately, glycolysis produces two ATP molecules and six NADH molecules per unit of glucose. In normal tissues, most of the pyruvate is directed into the mitochondrion to be converted into acetyl-CoA by the action of pyruvate dehydrogenase (PDH) or transaminated to form alanine (Marie, S. Shinjo, S. 2011; DeBerardinis, R.J. 2012).
FIGURE 01: The glycolytic pathway
FIGURE 02: The main routes of glucose utilization. Although it is not the only possible glucose ways, these four paths are most significant in terms of quality of glucose that flows through them in the majority of cells.
According to Marie and Shinjo (2011), for normal cells to produce two viable daughter cells at mitosis, all the cellular contents must be replicated, and energy is necessary for this to happen. Glucose participates in cellular energy production with two ATP synthesis through glycolysis and up to 36 ATPs through its complete catabolism by the TCA cycle and OXPHOS (oxidative phosphorylation). The large requirements for nucleotides, amino acids, and lipids for the daughter cells are provided by intermediate metabolites of these pathways.
In addition to glucose, glutamine is the other molecule catabolized in appreciable quantities for most mammalian cells in culture. Both molecules supply carbon, nitrogen, free energy, and reducing equivalents necessary to support cell growth and division. This means that glucose, in addition to being used for ATP synthesis, should also be diverted to macromolecular precursors such as acetyl-CoA for fatty acids, glycolytic intermediates for non-essential amino acids, and ribose for nucleotides to generate biomass (Marie, S. Shinjo, S. 2011; Nelson, D & Cox, M. 2011; Stryer, L. et al. 2008).