Glycerol phosphate shuttle, glycolysis

Because the 2 NADH formed in glycolysis are transported by the glycerol phosphate shuttle in this case, they each yield only 1.5 ATP, as already described. On the other hand, if these 2 NADH take part in the malate-aspartate shuttle, each yields 2.5 ATP, giving a total (in this case) of 32 ATP formed per glucose oxidized. Most of the ATP—26 out of 30 or 28 out of 32—is produced by oxidative phosphorylation only 4 ATP molecules result from direct synthesis during glycolysis and the TCA cycle. 

Oxidation of 2 molecules each of isocitrate, n-ketoglutarate, and malate yields 6 NADH Oxidation of 2 molecules of succinate yields 2 [FADHg] Oxidative phosphorylation (mitochondria) 2 NADH from glycolysis yield 1.5 ATP each if NADH is oxidized by glycerol-phosphate shuttle 2.5 ATP by malate-aspartate shuttle + 3 + 5... 

Six ATPs will be synthesized if the aspartate-malate shuttle is used to transfer NADH generated through glycolysis to NADH in the mitochondrial matrix four molecules of ATP will be made if the glycerol phosphate shuttle delivers the electrons to ubiquinone in the inner mitochondrial membrane. 

The answer is b. (Murray, pp 123-148. Scriver, pp 2367-2424. Sack, pp 159-175. Wilson, pp 287-317.) Aerobic glycolysis can be defined as the oxidative conversion of glucose to two molecules of pyruvate. In the process, two molecules of ATP and two molecules of NADH are produced. Since reducing equivalents from the two molecules of NADH produced in the cytoplasm must be transported into the mitochondrion for oxidation, it is not known how many ATP molecules are produced. On the assumption that two ATP molecules are formed per molecule of NADH oxidized via the glycerol phosphate shuttle, the ATP yield in aerobic glycolysis can be calculated as six ATP molecules per mole of glucose utilized. 

A summary of the sources of ATP produced from one molecule of glucose is provided in Table 10.2. ATP production from fatty acids, the other important energy source, is discussed in Chapter 12. Several aspects of this summary require further discussion. Recall that two molecules of NADH are produced during glycolysis. When oxygen is available, the oxidation of this NADH by the ETC is preferable (in terms of energy production) to lactate formation. The inner mitochondrial membrane, however, is impermeable to NADH. Animal cells have evolved several shuttle mechanisms to transfer electrons from cytoplasmic NADH to the mitochrondrial ETC. The most prominent examples are the glycerol phosphate shuttle and the malate-aspartate shuttle. 

Electron transfer pathways depend on reactions in both compartments. For example, NADH is produced in both the cytoplasm and the mitochondria. NADH equivalents from glycolysis must be transported into the mitochondria by the glycerol-phosphate shuttle or malate-aspartate shuttle. Furthermore, ATP that is produced in the mitochondria must be transported specifically to the cytoplasm to support the energy needs of many reactions. 

Figure 7-4. The electron transport chain. Electrons enter from NADH to complex I or succinate dehydrogenase, which is complex II. Electrons derived from glycolysis through the glycerol-3-phosphate shuttle, complex I, and complex II join at coenzyme Q and are transferred to oxygen as shown. As electrons pass through complexes I, III, and IV, protons are transported across the membrane, creating a pH gradient.

There are two shuttle systems the glycerol-3-phosphate shuttle found in skeletal muscle and nerve cells and the oxaloacetate-malate shuttle foimd in heart and liver cells. Because skeletal muscle produces the majority of the ATP for the body, it is the glycerol-3-phosphate shuttle that is used most commonly when discussing metabolic energy )delds. In Example 22.1, calculation of the ATP harvest of glycolysis is based on this shuttle. 

The main drawback of the glycerol-3-phosphate shuttle is that only two ATP are produced for each cytoplasmic NADH. The reason is that the electrons are shuttled to FADHj, which )delds only two ATP by oxidative phosphorylation. (The energy yield of the oxidation of mitochondrial NADH is three ATP.) Thus the total energy yield from glycolysis imder aerobic conditions in muscle and nerve cells is two ATP, produced by substrate level phosphorylation, plus four ATP (two ATP per NADH), produced by oxidative phosphorylation. This provides an energy yield of six ATP per glucose. 

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