1. ENERGY

2. The Importance of Energy Changes and Electron Transfer in Metabolism

3. Lecture Objectives What Are Standard States for Free-Energy Changes?
What Is a Modified Standard State for Biochemical Applications?
What Is Metabolism?
How Are Oxidation and Reduction Involved in Metabolism?
How Are Coenzymes Used in Biologically Important Oxidation–Reduction Reactions?
How Are the Production and Use of Energy Coupled?
How Is Coenzyme A Involved in Activation of Metabolic Pathways?

4. The most useful criterion for predicting spontaneity for a process is the change in free energy, DG,
A spontaneous process: one that takes place without outside addition of energy
note that “spontaneous” carries no indication of rate
A nonspontaneous process: one that takes place with outside addition of energy
G < 0, spontaneous, exergonic, energy released
G > 0, nonspontaneous, endergonic, energy required
G = 0 the system is at equilibrium

5. Free Energy Change Free Energy Change : G at any conditions
Standard state of ΔG (= ΔG°) at standard conditions
for pure solids and liquids, the pure substance
for gases, the gas at a pressure of 1 atm
for solutions, a concentration of 1 mol/L

6. when the reaction is at equilibrium,  G = 0
if we can determine the concentration of reactants and products at equilibrium, we can determine Keq and, from it, the change in free energy for conversion of one mole of reactant to product(s).

7. Standard free energy change, G°, assumes a concentration of 1 M
if [H+] = 1 M, then pH = 0
but the pH in most cells is near the neutral range
For biochemical reactions, we define a different standard state for the concentration of H+ called modified standard state
standard state for [H+] = 10-7 M, pH = 7.0
this modified standard state is given the symbol G°’

8. ATP Is the Universal Currency of Free Energy in Biological Systems
ATP is a nucleotide consisting of an adenine, a ribose, and a triphosphate unit . The active form of ATP is usually a complex of ATP with Mg2+ or Mn2+
ATP is an energy-rich molecule because its triphosphate unit contains two phosphoanhydride bonds. A large amount of free energy is liberated when ATP is hydrolyzed to adenosine diphosphate (ADP) and orthophosphate (Pi) or when ATP is hydrolyzed to adenosine monophosphate (AMP) and pyrophosphate (PPi).

9. Some biosynthetic reactions are driven by hydrolysis of nucleoside triphosphates that are analogous to ATP namely, guanosine triphosphate (GTP), uridine triphosphate (UTP), and cytidine triphosphate (CTP).

10. Consider the hydrolysis of ATP
the experimental value of K’eq = 2.23 x 105
because G°’ < 0, this process is spontaneous and energy is released D
G°' =
-30.5 kJ•mol -1
= kcal mol

11. The coupling of energy-producing and energy-requiring reactions is a central theme in the metabolism of all organisms central to this process is ATP

12. Coupled Reactions
Example: calculate G°’ for this reaction involving phosphoenolpyruvate (PEP) and decide whether or not it is spontaneous
use the following information
ADP PEP
ATP + Pyruvate

13. Coupled Reactions  G ⁰’= - 30.5 kJ.mol ⁻1
phosphorylation of ADP to ATP requires energy
ADP + Pi + H ATP + H2O
 G ⁰’= kJ.mol ⁻1
hydrolysis of ATP to ADP releases energy
ATP + H2O ADP + Pi + H+
 G ⁰’= kJ.mol ⁻1

15. Nature of Metabolism
Metabolism: the chemical reactions of biomolecules
catabolism: the breakdown of larger molecules into smaller ones; an oxidative process that releases energy
anabolism: the synthesis of larger molecules from smaller ones; a reductive process that requires energy
oxidation: the loss of electrons; the substance that loses the electrons is called a reducing agent
reduction: the gain of electrons; the substance that gains the electrons is called an oxidizing agent

18. Stages of Catabolism. The extraction of energy from fuels can be divided into three stages

20. Redox Coenzymes
Oxidation and reduction are most easily recognized by writing balanced half-reactions
conversion of ethanol to acetaldehyde is a two-electron oxidation
conversion of pyruvate to lactate is a two-electron reduction

21. NAD+/NADH

22. Nicotinamide adenine dinucleotide (NAD+) is a biological oxidizing agent

23. NADPH is a reducing agent used in anabolic reactions

24. FAD/FADH2

25. FAD/FADH2
FAD participates in several types of enzyme-catalyzed oxidation/reduction reactions
one is the oxidation of a C-C bond in a fatty acid hydrocarbon chain to a C=C bond - C H 2 = + e F A D
Oxidation of the hydrocarbon chain:
Reduction of FAD:
+ -CH=CH-

27. High Phosphoryl Transfer Potential Compounds.
These compounds have a higher phosphoryl transfer potential than that of ATP and can be used to phosphorylate ADP to form ATP.

28. Sources of ATP During Exercise In the initial seconds, exercise is powered by existing high phosphoryl transfer compounds (ATP and creatine phosphate). Subsequently, the ATP must be regenerated by metabolic pathways.

29. Although the total quantity of ATP in the body is limited to approximately 100 g, the turnover of this small quantity of ATP is very high.
For example, a resting human being consumes about 40 kg of ATP in 24 hours. During strenuous exertion, the rate of utilization of ATP may be as high as 0.5 kg/minute. For a 2-hour run, 60 kg of ATP is utilized. Clearly, it is vital to have mechanisms for regenerating ATP.

30. Motion, active transport, signal amplification, and biosynthesis can occur only if ATP is continually regenerated from ADP . The generation of ATP is one of the primary roles of catabolism. The carbon in fuel molecules such as glucose and fats is oxidized to CO2, and the energy released is used to regenerate ATP from ADP and Pi.

31. ATP-ADP Cycle. This cycle is the fundamental mode of energy exchange in biological systems.

32. Approximately 70% of our resting daily energy requirement arises from work carried out by our largest organs: the heart, brain, kidneys, and liver.
Using their rate of oxygen consumption it can be estimated that each of these organs is using and producing several times its own weight in ATP each day.

33. The heart, which rhythmically contracts, is using this ATP for mechanical work.
In contrast, skeletal muscles in a resting individual use far less ATP per gram of tissue.
The kidney has an ATP consumption per gram of tissue similar to that of the heart and is
using this ATP largely for transport work to recover usable nutrients and maintain pH and
electrolyte balance.

34. Estimated Daily Use of ATP (g ATP/g tissue) Heart 16 Brain 6
The brain, likewise, uses most of its ATP for transport work, maintaining the ion gradients necessary for conduction of the nerve impulse.
The liver, in contrast, has a high rate of ATP consumption and utilization to carry out metabolic work (biosynthesis and detoxification).
Estimated Daily Use of ATP (g ATP/g tissue)
Heart 16
Brain 6
Kidneys 24
Liver 6
Skeletal Muscle (rest) 0.3
Skeletal Muscle (running) 24

35. All About Your Metabolic Energy Systems
1. FIRST RESPONDER: THE ATP-CP ENERGY SYSTEM
Speed: Fast Primary Fuel: Adenosine triphosphate and creatine phosphate, stored in your muscles ATP-CP athletes are fast, strong and explosive, specializing in brief, single-effort activities like swinging a golf club or baseball bat, Olympic weightlifting, high-jumping.
2. FAST AND FURIOUS: THE GLYCOLYTIC ENERGY SYSTEM
Speed: Medium-fast Primary Fuel: Carbohydrate Sample Activities: Glycolytic athletes specialize in activities lasting 30 seconds to two minutes or so. Traditional strength training; 200- to 400-meter sprinting; 50-meter freestyle swimming.

36. cycling, running — all need exceptional aerobic capacity.
3. LONG, SLOW BURN: THE OXIDATIVE ENERGY SYSTEM
Speed: Slow to medium Primary Fuel: Fat Sample Activities: Jogging, slow swimming, cycling, walking, hiking, martial arts, continuous-action team sports (basketball, football).
cycling, running — all need exceptional aerobic capacity.
“We’re predominantly aerobic creatures”.

37. Anaerobic Glycolysis the conversion of glucose to lactate is exergonic
phosphorylation of ADP is endergonic
the two are coupled for a conservation of 61.0 kJ•mol-1 (33%) for use in anaerobic metabolism

38. Glucose to CO2 and H2O
Under aerobic conditions, glucose is oxidized to carbon dioxide and water
the efficiency of the energy conservation under aerobic conditions is approximately 34%

39. Activation A step frequently encountered in metabolism is activation
activation: the formation of a more reactive substance

40. Coenzyme A
following is a structural formula for acetyl coenzyme A

42. Coenzyme A
The metabolically active form of a carboxylic acid is an acyl-CoA thioester.

43. Metabolic Processes Are Regulated in Three Principal Ways
Metabolism is regulated by controlling : (1) the amounts of enzymes (2) their catalytic activities and (3) the accessibility of substrates. The amount of a particular enzyme depends on both its rate of synthesis and its rate of degradation. The level of most enzymes is adjusted primarily by changing the rate of transcription of the genes encoding them.

44. END Of CHAPTER 15