Biochemical Energetics and Metabolism (Chem/Biochem 114B)

Course Details
Website
Office Hours Exams

http://webct.ucsd.edu
Fri., 5:00-6:00 PM, 4254 Urey Hall Mid-term (in class, 35%), Fri., Feb. 10 Final (65%) ,Fri., Mar. 23 NO make up exams Gone over in sections
A01, 02, 03 A04, 08 A05, 06, 07
2

Problem sets TAs

John Zuris jzuris@ucsd.edu Kevin Lefever klefever@ucsd.edu Nathaniel Woodcohan nwoodcoh@ucsd.edu

Outline
Text Biochemistry (7th Edition). Berg, Tymoczko and Stryer, W. H. Freeman and Company, New York. 2011.

Topic
Carbohydrates Citric Acid Cycle, Oxidative Phosphorylation, Midterm Photosynthesis, Calvin Cycle (35%) Glycogen, Fatty Acids Proteins Nucleotides, Lipids

Time
Weeks 1-2 Weeks 2-5

Weeks 6-7
Weeks 7-8 Weeks 9-10 Weeks 10
3

Final (65%)

Metabolic control

Problems from the textbook gone over in section the following week

Syllabus

How to take notes

Lectures are guided tour of detailed information in the textbook Overall important points from Lecture

Details from the textbook reading

Lecture powerpoints available before the class

Why study metabolism?

Metabolism is essential to life Metabolic Disorders lead to diseases
Obesity and diabetes Aging (caloric restriction)

Prevalence of Obesity among U.S. Adults, BRFSS, 1985

<10%

10-15%

>15%
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Prevalence of Obesity among U.S. Adults, BRFSS, 1998

<10%

10-15%

>15%
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Growing Plague of Obesity

and
type II diabetes
1.1 million people died of diabetes in 2005 (WHO)
50% increase expected over next 10 years

Childhood obesity
Metabolic syndrome Insulin resistance Hypertension Cardiovascular disease

Caloric restriction and ageing

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Caloric restriction and ageing

Left: adequate nutrition (weight 180lb; BMI 26.0 kg/m2) Right: 7 years of dietary restriction (weight 134lb; BMI 19.4 kg/m2)
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Reactions are coupled

How to study metabolism

Overall reaction Key metabolites (i.e. reactants, products and intermediates) Key mechanisms Regulation (i.e., rate-determining steps and key enzymes) Chemical logic behind pathways

Important concepts
1. Overall principle 2. Difference between G and G0 3. Energy currency ATP and its equivalents 4. Coupled reactions (calculation)

5. Oxidation states
6. Typical carriers 7. Typical reacations

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Overall Principle
Metabolism
Catabolism
Break-down Generates energy (exergonic) Oxidation High-energy compounds (e.g., ATP) Requires energy (endergonic) Reduction

Anabolism
Synthesize Mechanical work Transport

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Catabolism

Anabolism

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Gibbs Free Energy

A+B
Reactants

C+D
Products

Standard State, at equilibrium

G 0

G RT ln Keq
'o

G Negative exergonic- Spontaneous reaction G Positive endergonic- Nonspontaneous reaction

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Chapter 8 Section 2. Thermodynamics

A feeling for concentrations mass action

G Negative exergonic- Spontaneous reaction How does ratio of Products/Reactants affect reaction? ln( ) But, very hard More Products to know 100 + 4.61 than reactant and Reactants 10 + 2.3 product 1 0 concentrations in living cells 0.1 - 2.3 More Reactants use G than 0.01 - 4.6
Products
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Energy released from oxidation of metabolic fuels are conserved in synthesis of highenergy compounds

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High-Energy Compounds
Pi transferred spontaneously to ADP

Pi transferred spontaneously

20

Adenosine triphosphate (ATP)

2-10 mM in cell

High energy b and g phosphates

ATP ADP + Pi G = -30.5 kJ/mol ATP AMP + PPi G = -45.6 kJ/mol

21

Rationalizing the energy in high-energy compounds resonance stabilization

Electrostatic repulsion

Hydration: more water molecules bind more effectively to ADP and Pi

22

Exergonic reactions drives endergonic reactions

Will the reaction proceed? What is the G?

A+B
D+E

C+D
F+G

G + endergonic
G exergonic G + G = x

A+B+E

C+F+G
Gs are additive

Coupled Reactions

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Coupled Reactions
First step in breaking down glucose (i.e., glycolysis) is adding a phosphate to glucose. But, how do we get a phosphate on to glucose?

24

High-Energy Compounds
Compounds above ATP can promote synthesis of ATP from ADP and Pi

25

Coupled Reactions
How do we get a phosphate on to ADP?

26

Oxidation of carbon fuels: Stages of catabolism

digestion

degradation

oxidation

27

The more reduced a carbon is to begin with, the more free energy is released by its oxidation

28

Consider the carbon atom below Methane d+

Electronegativity
Carbon Dioxide d+

d+

H C H

d-

d-

C O

d+

d-

Hd+
Carbon owns 8 electrons reduced Carbon owns 0 electrons oxidized

Power of an atom when in a molecule to attract electron to itself

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Electronegativity Scale

Electron withdrawing

Linus Pauling, General Chemistry, W.H. Freeman, San Francisco, 1970. Chapter 6

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Oxidation states of carbon # electrons

# electrons belonging to carbon belonging to carbon

Lehninger (4th ed.) 13-13

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Oxidization (lose electron)

Oxidation and reduction

1. Electron: Loss=oxidation; Gain=reduction
Example: Mg + Cl2 -> Mg2+ + 2ClMagnesium loses electrons (oxidized) the chlorines gain electrons (reduced)

2. Hydrogen: Loss=oxidation; Gain=reduction

Example: CH4 + 2O2 -> CO2 + 2H2O the carbon is oxidized (loses all four hydrogens) part of the oxygen is reduced (gains hydrogen)

3. Oxygen: Gain=oxidation; Loss=reduction

Example: 2H2 + O2 -> 2H2O the hydrogen is oxidized and the oxygen is reduced
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Activated carriers

Oxidized form: accept electron Reduced form: donate electron NAD+: R=H NADP+: R=PO32-

Oxidized form of nicotinamide adenine dinucleotide (NAD)

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Activated carriers

Oxidized form of flavin adenine dinucleotide (FAD)

34

Activated carriers

35

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Activated carriers

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Typical reactions

38

Typical reactions

39

Typical reactions

40

Typical reactions

41

Typical reactions

42

Typical reactions

43

Control of metabolic processes

1. Control the amounts of enzymes (genetic control) 2. Control catalytic activity A. Allosteric control

B. Covalent modification

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Control of metabolic processes

Control catalytic activity C. Energy status

D. Substrate accessibility (compartmentation)

45

Compartments
Glycolysis cytoplasm

Oxidative Phosphorylation mitochondrion

Compartments, therefore transport required

46

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Organ Specialization
Liver gluconeogenesis (synthesis of glucose)

Adipose tissues (fat) storage triacylglycerols

48

Summary
1. Metabolic reactions are coupled

2. High energy compounds, e.g. ATP, drive metabolic reactions

3. Oxidation of carbon fuels provide energy 4. Metabolic pathways contain recurring activated carriers and key reactions 5. Metabolic processes are well regulated

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Important concepts
1. Overall principle 2. Difference between G and G0 3. Energy currency ATP and its equivalents 4. Coupled reactions (calculation)

5. Oxidation states
6. Typical carriers 7. Typical reacations

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We will go through this figure in details

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