1. Tymoczko • Berg • Stryer © 2015 W. H. Freeman and Company
Biochemistry:
A Short Course
Third Edition
CHAPTER 15
Metabolism: Basic
Concepts and Design
© 2015 W. H. Freeman and Company

2. Chapter 15 Outline

3. The generation of energy from food occurs in three stages:
Large molecules in food are broken down into smaller molecules in the process of digestion.
The many small molecules are processed into key molecules of metabolism, most notably acetyl CoA.
ATP is produced from the complete oxidation of the acetyl component of acetyl CoA.

4. Figure 15. 1 Stages of catabolism
Figure 15.1 Stages of catabolism. The extraction of energy from fuels can be divided into three stages.

5. Energy is required to power muscle contraction, cell movement, and biosynthesis.
Phototrophs obtain energy by capturing sunlight.
Chemotrophs obtain energy through the oxidation of carbon fuels.
Basic principles govern energy manipulations in all cells:
Molecules are degraded or synthesized stepwise in a series of reactions termed metabolic pathways.
ATP is the energy currency of life.
ATP can be formed by the oxidation of carbon fuels.
Although many reactions occur inside a cell, there are a limited number of reaction types involving particular intermediates that are common to all metabolic pathways.
Metabolic pathways are highly regulated.

6. Metabolism is a series of linked reactions that convert a specific reactant into a specific product.
The entire set of cellular metabolic reactions are called intermediary metabolism.

7. Figure 15. 2 Glucose metabolism
Figure 15.2 Glucose metabolism. Glucose is metabolized to pyruvate in 10 linked reactions. Under anaerobic conditions, pyruvate is metabolized to lactate and, under aerobic conditions, to acetyl CoA. The glucose-derived carbon atoms of acetyl CoA are subsequently oxidized to CO2.

8. Metabolic pathways can be divided into two types:
Catabolic pathways combust carbon fuels to synthesize ATP.
Anabolic pathways use ATP and reducing power to synthesize large biomolecules.
Some pathways, called amphibolic pathways, can function anabolically or catabolically.
Although anabolic and catabolic pathways may have reactions in common, the regulated, irreversible reactions are always distinct.

9. Figure 15. 3 Metabolic pathways
Figure 15.3 Metabolic pathways. [From the Kyoto Encyclopedia of Genes and Genomes (

10. Energy derived from fuels or light is converted into adenosine triphosphate (ATP), the cellular energy currency.

11. The hydrolysis of ATP is exergonic because the triphosphate unit contains two phosphoanhydride bonds that are unstable.
The energy released on ATP hydrolysis is used to power a host of cellular functions.

12. Figure 15. 4 Structures of ATP, ADP, and AMP
Figure 15.4 Structures of ATP, ADP, and AMP. These adenylates consist of adenine (blue); a ribose (black); and a tri-, di-, or monophosphate unit (red). The innermost phosphorus atom of ATP is designated Pα, the middle one Pβ, and the outermost one Pγ.

13. ATP has a phosphoryl-transfer potential intermediate between high phosphoryl- potential compounds derived from fuel molecules and acceptor molecules that require the addition of a phosphoryl group for cellular needs.

14. Figure 15.7 ATP has a central position in phosphoryl-transfer reactions. The role of ATP as the cellular energy currency is illustrated by its relation to other phosphorylated compounds. ATP has a phosphoryl-transfer potential that is intermediate among the biologically important phosphorylated molecules. High phosphoryl-transfer–potential compounds (1,3-BPG, PEP, and creatine phosphate derived from the metabolism of fuel molecules are used to power ATP synthesis. In turn, ATP donates a phosphoryl group to other biomolecules to facilitate their metabolism. [After D. L. Nelson and M. M. Cox, Lehninger Principles of Biochemistry, 5th ed. (W. H. Freeman and Company, 2009), Fig ]

15. Muscle contains only enough ATP to power muscle contraction for less than a second.
Creatine phosphate can regenerate ATP from ADP, allowing a short burst of activity as in a sprint.
Once the creatine phosphate stores are depleted, ATP must be generated by metabolic pathways.

16. Figure 15. 8 Sprint to the finish
Figure 15.8 Sprint to the finish. Creatine phosphate is an energy source for intense sprints. [David Stockman/AFP/Getty images.]

17. Phosphate and its esters are especially prominent in biology for several reasons;
Phosphate esters are thermodynamically unstable, yet they are kinetically stable.
Phosphate esters are stable because the inherent negative charges resist hydrolysis.
Because phosphate esters are kinetically stable, they are ideal regulatory molecules, added to molecules by kinases and removed by phosphatases.

18. ATP is the immediate donor of free energy for biological activities.
However, the amount of ATP is limited.
Consequently, ATP must be constantly recycled to provide energy to power the cell.

19. Figure 15. 10 The ATP–ADP cycle
Figure 15.10 The ATP–ADP cycle. This cycle is the fundamental mode of energy exchange in biological systems.

20. Oxidation reactions involve loss of electrons
Oxidation reactions involve loss of electrons. Such reactions must be coupled with reactions that gain electrons. The paired reactions are called oxidation-reduction reactions or redox reactions.
The carbon atoms in fuels are oxidized to yield CO2, and the electrons are ultimately accepted by oxygen to form H2O.
The more reduced a carbon atom is, the more free energy is released upon oxidation.
Fats are a more efficient food source than glucose because fats are more reduced.

21. Figure 15. 12 Prominent fuels
Figure 15.12 Prominent fuels. Fats are a more efficient fuel source than carbohydrates such as glucose because the carbon in fats is more reduced.

22. The essence of catabolism is capturing the energy of carbon oxidation as ATP.
Oxidation of the carbon atom may form a compound with high phosphoryl-transfer potential that can then be use to synthesize ATP.

26. Two characteristics are common to activated carriers:
The carriers are kinetically stable in the absence of specific catalysts.
The metabolism of activated groups is accomplished with a small number of carriers.

27. ATP is an activated carrier of phosphoryl groups
ATP is an activated carrier of phosphoryl groups. Other activated carriers are common in biochemistry, and often they are derived from vitamins.
Nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) carry activated electrons derived from the oxidation of fuels.

28. Figure 15. 13 A nicotinamide-derived electron carrier
Figure 15.13 A nicotinamide-derived electron carrier. (A) Nicotinamide adenine dinucleotide (NAD+) is a prominent carrier of high-energy electrons derived from the vitamin niacin (nicotinamide) shown in red. (B) NAD+ is reduced to NADH.

31. Figure 15.14 The structure of the oxidized form of flavin adenine dinucleotide (FAD). This electron carrier consists of the vitamin riboflavin (shown in blue) and an ADP unit (shown in black).

33. Figure 15. 15 Structures of the reactive parts of FAD and FADH2
Figure 15.15 Structures of the reactive parts of FAD and FADH2. The electrons and protons are carried by the isoalloxazine ring component of FAD and FADH2.

34. Nicotinamide adenine dinucleotide phosphate (NADP+) is an activated carrier of electrons for reductive biosyntheses.

36. Figure 15.16 The structure of nicotinamide adenine dinucleotide phosphate (NADP+). NADP+ provides electrons for biosynthetic purposes. Notice that the reactive site is the same in NADP+ and NAD+.

37. Coenzyme A (CoA or CoASH) is an activated carrier of acyl groups such as the acetyl group.
The transfer of the acyl group is exergonic because the thioester is unstable.

38. Figure 15.17 The structure of coenzyme A (CoA-SH).

40. Pantothenate, which is readily obtained from egg yolks, is a component of coenzyme A.
The pantothenate must be activated by pantothenate kinase before it can be incorporated into coenzyme A.
Mutations in pantothenate kinase result in neurodegeneration.

43. The B vitamins function as coenzymes.
Vitamins A, C, D, E, and K play a variety of roles, but do not serve a coenzymes.

45. Figure 15.18 Structures of some of the B vitamins.

47. Figure 15.19 Structures of some vitamins that do not function as coenzymes.

48. Homeostasis, a stable biochemical environment, is maintained by careful regulation of biochemical processes. Three regulatory controls are especially prominent:
The amount of enzymes present.
The catalytic activity of enzymes.
The accessibility of substrates.

49. Figure Homeostasis. Maintaining a constant cellular environment requires complex metabolic regulation that coordinates the use of nutrient pools.

50. The quantity of enzyme present can be regulated at the level of gene transcription.

51. Catalytic activity is regulated allosterically or by covalent modification.
Hormones coordinate metabolic activity, often by instigating the covalent modification of allosteric enzymes.

52. The energy status of the cell is often an important regulator of enzyme activity.
Two common means are used to assess energy status: energy charge and phosphorylation potential.

53. Figure 15. 21 Energy charge regulates metabolism
Figure 15.21 Energy charge regulates metabolism. High concentrations of ATP inhibit the relative rates of a typical ATP-generating (catabolic) pathway and stimulate the typical ATP-utilizing (anabolic) pathway.

54. Opposing reactions, such as fatty acid synthesis and degradation, may occur in different cellular compartments.
Regulating the flux of substrates between compartments is used to regulate metabolism.