III Bioenergetics and Metabolism 13 Principle of Bioenergetics 14 Glycolysis and the Catabolism 15 The Citric Acid Cycle 16 Oxidation of Fatty Acid 17 Amino Acid Oxidation and the Production of Urea 18 Oxidative Phosphorylation and Photophosphrylation 19 Carbohydrate Biosynthesis 20 Lipid Synthesis 21 Biosynthesis of Amino Acids, Nucleotides, and Related Molecules 22 Integration and Hormonal Regulation of Mammalian Metabolism

1.Biological Work Requires Energy 2.Two Laws of Thermodynamic Govern Energy Transformations 3.Metabolic Reactions Involve Energy Transformation 4.ATP Is The Energy Currency of The Cell 5.Cells Transfer Energy By Redox Reactions 6.Enzymes Are Chemical Regulators

Biological Work Requires Energy

The Flow of Electrons Can Do Biological Work

1.Biological Work Requires Energy 2.Two Laws of Thermodynamic Govern Energy Transformations 3.Metabolic Reactions Involve Energy Transformation 4.ATP Is The Energy Currency of The Cell 5.Cells Transfer Energy By Redox Reactions 6.Enzymes Are Chemical Regulators

The First Law The total energy of any closed system in the universe does not change ---- remains constant. An Organism is an open system, it can exchange mater and energy with its surroundings. Because an organism can either make nor destroy energy, it must be adaptation that allow it to capture energy from its environment, convert it other forms, and use it for its own needs. Biological Energy Transformations Follow the Laws of Thermodynamics

Three Major Types of Energy Transformation Photosynthesis Cellular respiration Biological work

The second Law; The entropy (disorder) of the universe is increasing

1.Biological Work Requires Energy 2.Two Laws of Thermodynamic Govern Energy Transformations 3.Metabolic Reactions Involve Energy Transformation 4.ATP Is The Energy Currency of The Cell 5.Cells Transfer Energy By Redox Reactions 6.Enzymes Are Chemical Regulators

Living Organisms extract, transform, and use energy from their environment, usually in the form of either chemical nutrients or the radiant energy of sunlight.

Four Functions of Metabolism: 1.Extract energy; to obtain chemical energy by capturing solar energy or by degradation of energy- rich nutrients from the environment. 2.Convert materials; to convert nutrient molecules into the cell's own characteristic molecules. 3.Transfer energy; to polymerize monomeric precursors into macrobiomolecules (proteins, nucleic acids, lipids, polysaccharides). 4.Use the energy; to synthesize and degrade biomolecules required in specialized cellular functions.

Two Groups of Metabolism 1.Autotrophs ( 自养生物 ) such as photosynthetic bacteria and higher plants) can use carbon dioxide from the atmosphere as their sole source of carbon, from which they construct all their carbon- containing biomolecules. 2.Heterotrophs （异养生物） cannot use atmospheric carbon dioxide and must obtain carbon from their environment in the form of relatively complex organic molecules, such as glucose, proteins.

Cycling of carbon dioxide and oxygen Heterotrophs use the organic products of autotrophs as nutrients and return carbon dioxide to the atmosphere. The oxidation reactions that produce carbon dioxide also consume oxygen, converting it to water. Thus carbon, oxygen, and water are constantly cycled between the heterotrophic and autotrophic worlds, with solar energy as the driving force for this global process The balance between heterotrophs and autotrophs is very important for the environment.

Carbon, oxygen, and nitrogen recycle continuously but energy is constantly transformed into unusable forms such as heat. organisms cannot regenerate useful energy from energy dissipated as heat and entropy. Energy flows one way through the biosphere

Energy relationships between catabolic and anabolic pathways Catabolism （异化作用） : The pathway degrade organic nutrients into simple end products in order to extract chemical energy and convert it into a form useful to the cell. Anabolism （同化作用） : The pathway start with small precursor molecules and convert them to larger and more complex molecules and require the input of energy.

Catabolism is the degradative phase, and release energy, some of which is conserved in the formation of ATP and reduced electron carriers (NADH, NADPH, and FADH2) and the rest is lost as heat. Anabolism is the synthesis phase and input of energy, generally in the form of the phosphoryl group transfer potential of ATP and the reducing power of NADH, NADPH, and FADH2.

Three types of molecular metabolic pathways (1) Converging catabolic (2) Diverging anabolic (3) Cyclic pathway

Catabolic and anabolic pathways that connect the same two end points may employ many of the same enzymes. But, 1.invariably at least one of the steps is catalyzed by different enzymes, and they are the sites of separate regulation, 2.moreover, for both anabolic and catabolic pathways to be essentially irreversible, the reactions unique to each direction must include at least one that is thermodynamically very favorable.

Three thermodynamic quantities; 1.Gibbs free energy (G) and free-energy change, ΔG 2. Enthalpy (H) and Enthalpy change ΔH 3. Entropy (S) and Entropy change ΔS

Gibbs Free Energy (G); expresses the amount of energy capable of doing work during a reaction at constant temperature and pressure. Free-energy Change (ΔG); When ΔG°' is negative, the products contain less free energy than the reactants. The reaction will therefore proceed spontaneously to form the products under standard conditions. When ΔG°' is positive, the products of the reaction contain more free energy than the reactants. The reaction will therefore tend to go in the reverse direction if we start with 1.0 M concentrations of all components. The units of ΔG is joules/mole or calories/mole

Enthalpy (H ，焓 ); is the heat content of the reacting system. It reflects the number and kinds of chemical bonds in the reactants and products. Enthalpy Change (ΔH); When a chemical reaction releases heat, it is said to be exothermic; the heat content of the products is less than that of the reactants and ΔH has a negative value. Reacting systems that take up heat from their surroundings are endothermic and have positive values of ΔH. The units of ΔH is joules/mole or calories/mole

Entropy (S ，熵 ); is a quantitative expression for the randomness or disorder in a system. Entropy Change (ΔS); When the products of a reaction are less complex and more disordered than the reactants, the reaction is said to proceed with a gain in entropy. The units ΔS is joules/moledegree Kelvin.

In Biological Systems (at constant temperature and pressure) ΔG = ΔH - TΔS T is the absolute temperature. When entropy increases, ΔS has a positive sign. When heat is released by the system to its surroundings, ΔH has a negative sign. Either of these conditions, which are typical of favorable processes, will tend to make ΔG negative. In fact, ΔG of a spontaneously reacting system is always negative.

In Biological Systems Cells drive endergonic reactions by coupling them to exergonic reaction.

1.Biological Work Requires Energy 2.Two Laws of Thermodynamic Govern Energy Transformations 3.Metabolic Reactions Involve Energy Transformation 4.ATP Is The Energy Currency of The Cell 5.Cells Transfer Energy By Redox Reactions 6.Enzymes Are Chemical Regulators

1.ATP molecule has three main parts 2.ATP can donated energy through the transfer of a phosphate group 3.The Free-Energy Change for ATP Hydrolysis Is Large and Negative 4.ATP is kinetically stable toward nonenzymatic breakdown 5.The actual free energy of hydrolysis (ΔG) of ATP in living cells is very different

ATP molecule has three main parts 1.Nitrogen-containing organic base 2.Ribose, a five-carbon sugar 3.Three phosphate groups

ATP can donated energy through the transfer of a phosphate group Heterotrophic cells obtain free energy in a chemical form by the catabolism of nutrient molecules and use that energy to make ATP from ADP and Pi. ATP then donates some of its chemical energy to endergonic processes such as the synthesis of metabolic intermediates and macromolecules from smaller precursors, transport of substances across membranes against concentration gradients, and mechanical motion.

ATP + H 2 O ADP + Pi ∆G = -32kj/mole Glucose + Fructose Sucrose ∆G = 27kj/mole ∆ G = -5kj/mole 88 X (ADP + Pi ATP) ∆ G = 32 X 88 = 2560kj/mole Glucose + 6O 2 6CO 2 + 6H 2 O ∆ G = -2840kj/mole ∆ G = -24

The Free-Energy Change for ATP Hydrolysis Is Large and Negative

Although its hydrolysis is highly exergonic (ΔG°' = kJ/mol), ATP is kinetically stable toward nonenzymatic breakdown at pH 7 because the activation energy for ATP hydrolysis is relatively high. Rapid cleavage of the phosphoric acid anhydride bonds occurs only when catalyzed by an enzyme.

The actual free energy of hydrolysis (ΔG) of ATP in living cells is very different (not 30.5 kJ/mol). Furthermore, the cytosol contains Mg2+, which binds to ATP and ADP. In most enzymatic reactions that involve ATP as phosphoryl donor, the true substrate is MgATP2- and the relevant ΔG°' is that for MgATP2- hydrolysis. ΔG for ATP hydrolysis in intact cells, usually designated ΔG P, is much more negative than ΔG°' in most cells ΔG P ranges from -50 to -65 kJ/mol.

Other Phosphorylated Compounds and Thioesters Also Have Large Free Energies of Hydrolysis 1.Phosphoenolpyruvate （磷酸烯醇式丙酮酸） 2. 1,3-bisphosphoglycerate （甘油 -1,3- 二磷酸） 3.Phosphocreatine （磷酸肌酸） 4.Thioesters （硫酯）

1.Phosphoenolpyruvate （磷酸烯醇式丙酮酸）

2. 1,3-bisphosphoglycerate （甘油 -1,3- 二磷酸）

3. Phosphocreatine （磷酸肌酸）

4. Thioesters （硫酯）

ATP Provides Energy by Group Transfers, Not by Simple Hydrolysis

Two groups of phosphate compounds in living organisms. High-energy compounds; ΔG°' ＜ -25 kJ/mol "low-energy" compounds; ΔG°' ＞ -25 kJ/mol Flow of Phosphoryl Groups

1.Biological Work Requires Energy 2.Two Laws of Thermodynamic Govern Energy Transformations 3.Metabolic Reactions Involve Energy Transformation 4.ATP Is The Energy Currency of The Cell 5.Cells Transfer Energy By Redox Reactions 6.Enzymes Are Chemical Regulators

Electron Carriers Transfer Energy When an electron, either singly or as part of a hydrogen atom, is removed from an organic compound, it takes with it some of the energy stored in the chemical bond of which it was a part. Cells contain a variety of molecular energy transducers, which convert the energy of electron flow into useful work. (such as NAD +, NADP +, FMD and FAD)

Electrons are transferred from one molecule (electron donor) to another (electron acceptor) in one of four different ways: 1. Directly as electrons Fe 2 + Cu 2 Fe 3 Cu + 2. As hydrogen atoms. AH 2 A 2e 2H + AH 2 + B A BH 2 3. As a hydride ion (:H), which has two electrons. NAD-linked dehydrogenases, 4. Through direct combination with oxygen. R-CH 3 + O 2 R-CH 2 -OH

Soluble Electron Carriers 1.Nicotinamide adenine dinucleotide (NAD + ， 烟酰胺腺嘌呤二核苷酸 ) 2.Nicotinamide adenine dinucleotide phosphate (NADP+ ， 磷酸烟酰胺腺嘌呤二核苷酸 ) 3.Flavin mononucleotide (FMN ， 黄素单核苷酸 ) 4.Flavin adenine dinucleotide (FAD ， 黄素腺嘌呤 二核苷酸 )