Generation of Energy from Dietary Fuels

Chapter 5 Generation of Energy from Dietary Fuels



I. Energetics of Metabolic Pathways
A. Overview
1. Free energy change (ΔG) for a biochemical reaction indicates its tendency to proceed and the amount of free energy it will release or require.

2. Coupled reactions share a common intermediate.

3. ATP-ADP cycle is the most common mechanism of energy exchange in biologic systems.

4. Redox coenzymes serve as carrier molecules for hydrogen and electrons during biologic oxidation-reduction reactions

B. Change in free energy (ΔG)
1. A decrease in free energy for a biochemical reaction, or sequence of reactions, indicates its tendency to proceed.

2. The amount of decrease in free energy in kcal/mole is the amount of free energy a reaction will release or require.

3. A reaction that requires a free energy input must be coupled to another reaction that releases at least that much energy.

Free energy change: tendency to react, energy released or used


C. Coupled reactions
1. When two reactions share a common intermediate, they are considered to be coupled,

a. For example, the common intermediate C couples these two reactions:

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b. Overall coupled reaction (A + B image X) proceeds spontaneously in a forward direction if the sum of ΔG values of the individual reactions is negative.

Coupled reactions: common intermediate required


2. Metabolic pathways consist of a series of coupled reactions linked by common intermediates (Fig. 5-1).

a. The ΔG values are additive for all pathway reactions.

(1) An energetically favorable reaction (e.g., hydrolysis of ATP) drives an energetically unfavorable coupled reaction in the forward direction.

b. If ΔG for consecutive reactions is negative, the reactions operate spontaneously in the forward direction.
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5-1 Processes that affect flow through metabolic pathways. In the absence of such processes, individual reversible reactions eventually reach equilibrium, and the flow of metabolites through a pathway ceases. For example, a genetic defect or inhibitor that reduces production of B also decreases operation of the pathway from fuel → A → Y.



Negative ΔG: allows coupled reactions to proceed spontaneously in a forward direction


D. ATP-ADP cycle (Fig. 5-2)
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5-2 The ATP-ADP cycle. Energy stored in reduced fuel molecules is extracted during oxidative metabolism (i.e., respiration) and converted to ATP. Hydrolysis of ATP releases energy that cells use for major types of energy-requiring processes (thick arrows).



ATP-ADP cycle: most common mechanism of energy exchange in biologic systems


1. Hydrolysis of high-energy bonds in ATP has a ΔG of about 7 kcal/mol.

ATP: large negative ΔG values can drive many energy-requiring reactions


2. Hydrolysis of other nucleoside triphosphates and other high-energy compounds provides energy for a variety of metabolic processes. For example:

a. GTP during ribosomal steps of protein synthesis

b. CTP during lipid synthesis

c. UTP during polysaccharide synthesis

d. Phosphocreatine in muscle replenishes ATP.

E. Redox coenzymes (Fig. 5-3)
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5-3 Role of redox coenzymes as electron carriers. Oxidized coenzymes (light shading) are reduced during catabolism. Reduced coenzymes (dark shading) are used in reductive biosynthesis (left) or in oxidative phosphorylation to generate ATP (right).



Redox coenzymes: carrier molecules for hydrogen and electrons during biologic oxidation-reduction reactions


1. Nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) are the major electron acceptors in the catabolism of fuel molecules.

a. Reduced forms of NAD+ and FAD (i.e., NADH and FADH2) transfer electrons to the electron transport chain.

b. Electrons are ultimately transferred to O2 by the electron transport chain with the coupled formation of ATP (i.e., oxidative phosphorylation).

NAD+ and FAD: electron and hydrogen carriers


NAD+/NADH: catabolic reactions


2. NADPH (a phosphorylated derivative of NADH) is the primary electron donor in reductive biosynthetic reactions (e.g., synthesis of fatty acids, cholesterol, and steroids).

NADP+/NADPH: anabolic reactions


II. Introduction to Intermediary Metabolism
A. Overview
1. Catabolism of foodstuffs to generate ATP occurs in three stages: digestion to small components, formation of acetyl CoA, and oxidation of acetyl CoA in the citric acid cycle (CAC).

2. Metabolic pathways are localized to particular cellular sites.

3. There are five common aspects of metabolic pathways: reaction steps, regulated steps, unique characteristics, pathway interfaces, and clinical relevance.

B. Catabolic stages (Fig. 5-4).
1. Breakdown of large dietary constituents (i.e., carbohydrates, fats, and proteins) to their small building blocks by digestive enzymes

2. Formation of acetyl CoA by degradation of the products of digestion (e.g., glucose, fatty acids, glycerol, and amino acids)

3. Oxidation of acetyl CoA in the CAC and the flow of electrons through the electron transport chain with coupled formation of ATP (i.e., oxidative phosphorylation)
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5-4 Three stages in catabolism of the energy-yielding major nutrients. Notice the central role of pyruvate and acetyl CoA. Oxidative phosphorylation, the formation of ATP coupled to the flow of electrons (e−) through the electron transport chain (ETC), generates most of the ATP resulting from catabolism.



Acetyl CoA: product of fat and glucose oxidation



a. Acetyl CoA is produced by fat oxidation and glucose oxidation.

b. Acetyl CoA is used in fat synthesis, cholesterol synthesis, ketone body synthesis, and formation of acetylated molecules.

Acetyl CoA: a focal point in metabolism


C. Compartmentation of metabolic pathways
1. Mitochondria

a. Matrix

(1) Production of acetyl CoA, CAC, β-oxidation of fatty acids, ketogenesis

b. Inner membrane: oxidative phosphorylation

2. Cytosol

a. Glycolysis, glycogenesis, glycogenolysis, pentose phosphate shunt, fatty acid synthesis, steroid synthesis (i.e., smooth endoplasmic reticulum), protein synthesis (i.e., rough endoplasmic reticulum)

3. Mitochondria and cytosol

a. Gluconeogenesis, urea cycle, heme synthesis

4. Nucleus and mitochondria

a. DNA and RNA synthesis

Metabolic pathways occur in specific cellular sites (e.g., glycolysis in cytosol, CAC oxidative phosphorylation in mitochondria).


D. Five common perspectives for many metabolic pathways
1. Pathway reaction steps

a. Each reaction in a pathway has unique characteristics regarding substrates, products, enzymes, cofactors, and inhibitors.

2. Regulated steps

a. At least one step in a metabolic pathway is generally regulated by hormones or metabolites that restrict or accelerate the flow of metabolites through the pathway.

3. Unique characteristics

a. Each metabolic pathway has features that describe unique aspects of its function.

b. This provides insight into its contribution to metabolism.

4. Interface with other pathways

a. Many intermediates within one pathway are substrates for other pathways, providing a means for different pathways to interact.

5. Clinical relevance

a. Significant reduction in the activity of an enzyme catalyzing one step in a pathway, caused by a genetic defect or inhibitor, leads to accumulation of some metabolites and reduced levels of others, often with pathologic consequences.

b. Increased flow through a pathway results in toxic buildup (e.g., lactic acidosis).

6. These perspectives apply most easily to carbohydrate and lipid metabolism.

Organize learning of metabolic pathways around four categories.



a. Pathway reaction steps

b. Regulated steps

c. Unique characteristics

Related posts:

  1. Carbohydrates, Lipids, and Amino Acids: Metabolic Fuels and Biosynthetic Precursors
  2. Nitrogen Metabolism
  3. Gene Expression
  4. Proteins and Enzymes

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Jun 18, 2016 | Posted by in BIOCHEMISTRY | Comments Off on Generation of Energy from Dietary Fuels

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