lecture23_12_2_08 - Lecture 23 Chapter 27 The Integration...

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Chapter 27 The Integration of Metabolism Lecture 23 Chapter 35 Drug Development The role of the mitochondria is highly important. Metabolism Summary The basic strategy of catabolic metabolism is to form ATP, reducing power, and building blocks for biosynthesis. 1) ATP is the universal currency of energy . The high-phosphoryl potential of ATP enables it to serve as an energy source in muscle contraction, signal amplification, biosynthesis, etc. Thermodynamically unfavorable reaction sequences can be made highly favorable by coupling to hydrolysis of ATP . Metabolism Summary 2) ATP is generated by the oxidation of fuel molecules such as glucose, fatty acids, and amino acids . The common intermediate is acetyl CoA . The carbon atoms of the acetyl unit are completely oxidized to CO 2 with concomitant formation of NADH and FADH 2 by the citric acid cycle . The high-potential electrons from NADH and FADH 2 are transferred to the respiratory chain . The flow of electrons to O 2 leads to pumping of protons across the inner mitochondrial membrane. This proton gradient is used to make ATP. Glycolysis also makes ATP directly, but the amount is much less than that formed by oxidative phosphorylation . The oxidation of glucose to pyruvate yields 2 ATPs, whereas complete oxidation to CO 2 yields 30 ATPs. Metabolism Summary 3) NADPH is the major electron donor in reductive biosynthesis . In most biosyntheses, the product is more reduced than the precursor. The high-potential electrons required to drive these reactions come from NADPH. The pentose phosphate pathway supplies much of the needed NAPDH. 4) Biomolecules are constructed from a small set of building blocks . The highly diverse molecules of life are synthesized from a much smaller number of precursors. The metabolic pathways that generate ATP and NADPH also provide building blocks for biosyntheses of more complex biomolecules. For example, acetyl CoA , a common intermediate in the breakdown of molecules also supplies two-carbon units for a wide variety of biosyntheses, such as those leading to fatty acids , prostaglandins , cholesterol , etc.
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Metabolism Summary 5) Biosynthetic (anabolic) and degradative (catabolic) pathways are almost always distinct. Fatty acid synthesis differs from fatty acid degradation. Glycolysis and gluconeogenesis also differ. This separation enables both biosynthetic and degradative pathways to be thermodynamically favorable at all times. A biosynthetic pathway is made exergonic by coupling it to the hydrolysis of ATP. The separation of biosynthetic and degradative pathways also contributes to the effectiveness of metabolic control and regulation. Recurring Motifs are Common Anabolism and catabolism must be precisely controlled.
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