Pathways glycolytic

Two and twelve moles of ATP are produced, respectively, per mole of glucose consumed in the glycolytic pathway and each turn of the Krebs (citrate) cycle. In fat metaboHsm, many high energy bonds are produced per mole of fatty ester oxidized. Eor example, 129 high energy phosphate bonds are produced per mole of palmitate. Oxidative phosphorylation has a remarkable 75% efficiency. Three moles of ATP are utilized per transfer of two electrons, compared to the theoretical four. The process occurs via a series of reactions involving flavoproteins, quinones such as coenzyme Q, and cytochromes. 

The chemical reaction catalyzed by triosephosphate isomerase (TIM) was the first application of the QM-MM method in CHARMM to the smdy of enzyme catalysis [26]. The study calculated an energy pathway for the reaction in the enzyme and decomposed the energetics into specific contributions from each of the residues of the enzyme. TIM catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) as part of the glycolytic pathway. Extensive experimental studies have been performed on TIM, and it has been proposed that Glu-165 acts as a base for deprotonation of DHAP and that His-95 acts as an acid to protonate the carbonyl oxygen of DHAP, forming an enediolate (see Fig. 3) [58]. 

For many years hemoglobin was the only allosteric protein whose stereochemical mechanism was understood in detail. However, more recently detailed structural information has been obtained for both the R and the T states of several enzymes as well as one genetic repressor system, the trp-repressor, described in Chapter 8. We will here examine the structural differences between the R and the T states of a key enzyme in the glycolytic pathway, phosphofructokinase. 

All overview of the glycolytic pathway is presented in Figure 19.1. Most of the details of this pathway (the first metabolic pathway to be elucidated) were worked out in the first half of the 20th century by the German biochemists Otto Warburg, G. Embden, and O. Meyerhof. In fact, the sequence of reactions in Figure 19.1 is often referred to as the Embden-Meyerhof pathway. 

FIGURE 19.3 Just as a water pump must be primed with water to get more water out, the glycolytic pathway is primed with ATP iu steps 1 and 3 iu order to achieve net production of ATP iu the second phase of the pathway. 

In most animal, plant, and microbial cells, the enzyme that phosphorylates glucose is hexokinase. Magnesium ion (Mg ) is required for this reaction, as for the other kinase enzymes in the glycolytic pathway. The true substrate for the hexokinase reaction is MgATP. The apparent K , for glucose of the animal... 

The second half of the glycolytic pathway involves the reactions that convert the metabolic energy in the glucose molecule into ATP. Altogether, four new ATP molecules are produced. If two are considered to offset the two ATPs consumed in phase 1, a net yield of 2 ATPs per glucose is realized. Phase II starts with the oxidation of glyceraldehyde-3-phosphate, a reaction with a large... 

The remaining steps in the glycolytic pathway prepare for synthesis of the second ATP equivalent. This begins with the phosphoglycerate mutase reaction (Eigure 19.23), in which the phosphoryl group of 3-phosphoglycerate is moved... 

The glycolytic pathway described in this chapter begins with the breakdown of glucose, but other sugars, both simple and complex, can enter the cycle if they can be converted by appropriate enzymes to one of the intermediates of glycolysis. Figure 19.32 shows the mechanisms by which several simple metabolites can enter the glycolytic pathway. Fructose, for example, which is pro-... 

FIGURE 19.32 Mannose, galactose, fructose, and other simple metabolites can enter the glycolytic pathway. 

Fructose-6-phosphate generated in this way enters the glycolytic pathway directly in step 3, the second priming reaction. This is the principal means for channeling fructose into glycolysis in adipose tissue, which contains high levels of fructose. 

Determine the anticipated location in pyruvate of labeled carbons if glucose molecules labeled (in separate experiments) with " C at each position of the carbon skeleton proceed through the glycolytic pathway. 

Fothergill-Gilmore, L., 1986. The evolution of die glycolytic pathway. Trends in Biochemical Sciences 11 47—51. 

Most of the NADH used in electron transport is produced in the mitochondrial matrix space, an appropriate site because NADH is oxidized by Complex I on the matrix side of the inner membrane. Furthermore, the inner mitochondrial membrane is impermeable to NADH. Recall, however, that NADH is produced in glycolysis by glyceraldehyde-3-P dehydrogenase in the cytosol. If this NADH were not oxidized to regenerate NAD, the glycolytic pathway would cease to function due to NAD limitation. Eukaryotic cells have a number of shuttle systems that harvest the electrons of cytosolic NADH for delivery to mitochondria without actually transporting NADH across the inner membrane (Figures 21.33 and 21.34). 

The complete route of gluconeogenesis is shown in Figure 23.1, side by side with the glycolytic pathway. Gluconeogenesis employs three different reactions, catalyzed by three different enzymes, for the three steps of glycolysis that are... 

N/ JDPH is considerably greater than the need for ribose-5-phosphate. The next three steps thus return some of the five-carbon units to glyceraldehyde-3-phos-phate and fructose-6-phosphate, which can enter the glycolytic pathway. The advantage of this is that the cell has met its needs for N/VDPH and ribose-5-phosphate in a single pathway, yet at the same time it can return the excess carbon metabolites to glycolysis. 

FIGURE 23.40 Both ATP and NADPH (as well as NADH) can be produced by this version of the pentose phosphate and glycolytic pathways. 

Fothergill-Gilmore LA The evolution of the glycolytic pathway. Trends Biochem Sci 1986 11 47. 

Mature red blood cells do not have nuclei, mitochondria, or microsomes therefore red blood cell function is supported through the most primitive and universal pathway. Glucose, the main metabolic substrate of red blood cells, is metabolized via two major pathways the Embden-Meyerhof glycolytic pathway and the hex-ose monophosphate pathway (Fig. 1). Under normal circumstances, about 90% of the glucose entering the red blood cell is metabolized by the glycolytic pathway and 10% by the hexose monophosphate pathway. 

Deficiency of pyruvate kinase (PK) is the most common and well-characterized enzymatic deficiency involving the glycolytic pathway and causing hereditary he-... 

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