Review:

Metabolism what is it all about?

Key principles and important pathways we
talked about over the last 10 weeks.

Final exam:

al exam will be similar to the midterm just longer and more comprehensive.

e exam will have both multiple choice and open question, again, similar to the m

Key Concepts Week 1:

Introduction

Gibbs free energy:

A+B

C+D

Thermodynamic potential:
Energetic potential of this SPECIFIC reaction given
reactants and products concentration

Energetic potential

G RT ln K eq
'o

Redox reactions

G = nF E
n, number of electrons
F, faraday (96.48 kJmol-1V-1 or 23.06 kcalmol-1V-1)
E, electrical potential difference or
electromotive force or reduction potential
(volts)
For spontaneous process, G is negative,
and so E has to be positive
And like standard free energy G, there is a standard
reduction potential, E
6

Principles of metabolic flux

regulation
Allosteric regulation and feedbacks
Covalent modification
Genetic control (expression &
isozymes)
Substrate cycles

The Currencies of energy

ATP
Other Phosphorylated compounds
Coupled reactions
Theioesters and Aceytl-CoA

Oxidation reduction
Oxidation state for carbon
The redox currencies NAD+ and
FAD
Thermodynamics of redox reactions

Key Concepts Week 2:

Glycolysis

Understanding Glycolysis:
1. Overview of glycolysis
2. The reactions of glycolysis
1. Stage #1
2. Stage #2

3. Regulation of glycolysis

Glycolysis

You (at least some of you) where

able to piece up the order of glycolysis
without knowing anything about it!

Glycolysis: Stage 1 Energy investment

Glycolysis: Stage 2 Energy Recovery

x2

x2

x2

First Stage of Glycolysis: chemical logic

Isomerizaton in
reaction #2 is
required for the
cleavage into to
GAP in reaction
4 (and 5)
isomerization

Principles of metabolic flux

regulation
Allosteric regulation

Rxn #1,
Hexokinase:

Covalent modification

Substrate cycles

Genetic control
(expression & isozymes)

Rxn #3,
Phosphofructikinase:

Rxn #10,
Pyruvate kinase:

we are only covering PARTIAL list of regulatory mechanisms for these three enzym

Metabolic Fate of Pyruvate

17

Key Concepts Week 3:

Glycogen

Structure of Glycogen

Enough
Glucose

813sugars

Glycogen breakdown Process Diagram:

Glycogen Phosphorylase Mechanism

Glycogen breakdown Glycogen

Debranching Enzyme

Glucosyltransferase

Opposing Glycogen Pathways:

Synthesis & Degradation

Hormonal Control of Glycogen

Metabolism, the balance of phosphorylation of glycogen
phosphorylase and synthase

Glycogen Metabolism: Major

Phosphorylation/Dephosphorylation Systems

Glycogen
G1P

Glycolysis & Gluconeogenesis Pathways

Key Concepts Week 4:

Citric Acid Cycle

Citric acid cycle

1. Pyruvate Dehydrogenase
2. Overview of Citric acid cycle
3. Reactions of Citric acid cycle
4. Regulation
5. Reactions related to citric acid
cycle

How do the reaction happen with

the PDH complex

Citric acid cycle has catabolic and

anabolic roles
Catabolic: oxidize Acetyl
and make NADH/FADH2
(+GTP)

Anabolic: Intermediates are used as

in many biosynthetic pathways

Citric Acid Cyclc: the reactions

0. Pyruvate -> Acetyl-CoA
1. What are they key steps in this
reaction?
2. What co-factors are used?

1. Oxaloacetate -> Citrate

1. What is the challenge that the
enzyme faces?
2. Why does it faces that
challenge?
3. What can it do about it?

2. Citrate -> Iso-Citrate

1. What is the chemical logic?
2. Why is this reaction critical?

3. Isocitrate -> a-ketoglutarate

4. A-ketoglutarate -> SuccinylCoA
1. What other enzyme is this
similar to?

5. Succinyl-Co-A -> succinate

1. What is the mechanism?
2. How was it figured out?

6. Succinate -> Fumarate

1. Where is it happenning?

7. Fumarate -> Malate

1. Why is H2O added?

Phosphrylation of PDH is the main

regulatory mechanism

Regulation of Citric Acid Cycle

product inhibition

32

Key Reactions that

Replenish CAC Intermediates

Week 5: Oxidative
phosphorylation

Electron transport & oxidative

phosphorylation
1. Mitochondrion & power
plants
2. Electron transport
3. Oxidative phosphorylation

The mitochondria power plant

Invest energy
(oxidize pyruvate &
fatty acids)
Create a gradient
(proton different
across the inner
membrane)
Convert potential
energy to create
the source of
energy you are
interested in (ATP)

Overview of Electron Transport

Pokmon electron transport

chain
Exercise was too hard (will do better
next year) but I hope you learned
that the order of redox center matter
and they have to be matched by
physical distance and redox potential

Mitochondrial Electron-Transport Chain

Glycerophosphate Shuttle

FADH2 from beta-oxidation of fatty acids

s a unique carrier, it is hydrophobic and can move between different complexes.

make it a great entry point for multiple pathway (note Complex I and Complex II n

In our analysis of electron transport chain

we need to pay attention to the following
question for each and every step:
1.How do electrons move around?
2.How do proton move around?
3.What couples electron movement to
proton movement?

Using the H+ gradient

Model of F1F0-ATPase

How much energy (i.e. G) can

we really get from H+ gradient?
So far:

Gconc = 2.3 RT pH Gelec =zF

G = Gconc + Gelec = 2.3 RT pH + zF

Given the constant:

R = 0.0083145 kJ/K/mol
V z = +1

T = 310 K

pH = -1 F = 96.485 kJ/ V / mol

What will be the energy for the transport from inner membrane to matrix
fpr A SINGLE PROTOON?

We get:
G = 2.3* 0.0083145 (kJ/K/mol) *310 (K) * -1 +
1 * 96.485 (kJ/V/mol) * -0.168 (V) =

-22.1 kJ/mol

Week 6: Photosynthesis

Photosynthesis learning objectives

1. Light -> ATP & NADPH
2. NADPH & ATP & CO2 ->
Carbohydrates

Photosynthesis overview:

1. How is light absorbed?

2. How do electrons move
around?
3. How do ATP & NADPH are
made?

Energy Flow Through Photosynthetic

Antenna Complex

How do electron move around?

4
8

How many new H+ in

the Thylakoid per O2
generated?

12
Longboar
d

4 H+ from two water molecules 4 H+ from 2 QH2

Plus generation of 2 QH2
4 H+ transferred from Stroma

4+4+4=12

Calvin cycle has two key stages:

1. Production
2. Recovery

RuBP Carboxylase Mechanism

Week 7: Lipid metabolism

The two major players: Triacylglycerols

and cholesterol

Lipidshavevery
widerangesof
functions

cholesterol
53

Triacylglycerol & Cholesterol Transport

Lipoproteins/particles in Human Plasma

 Oxidation of Fatty
Acyl-CoAInside the
mitochondrion

Ketogenesis

Precursorto
cholesterol

Lipid Metabolism Summary

Biosynthesis of Fatty Acids

Box 20-3: Polyketide Synthesis

Weeks 8&9: Amino Acids

Protein degredation

Ubiquitin

Amino Acid Catabolism

Mobilizingtheammonia

Transamination

The Urea Cycle

7 Common Amino Acid Degradation

Products

Keyslide

AA Synthesis

Week 10: Integration

Integration and regulation

1. Interconnection of pathways
2. Tissue specialization and organs profiles.
3. Coupling between organs & hormone regulation
4. Homeostasis: Food intake, starvation and obesity

Assuming F1 is 10 mmol/h, what will be

the maximal rate of Fobjective, What will
be the different fluxes?

Metabolic Interrelationships: Brain, Adipose,

Muscle, Liver & Kidney

The pancreas is a feedback

controller of glucose blood levels!

Body metabolism will adjust to

starvation conditions

Initial adjustment increase

glucose biosynthesis

Secondary adjustment
utilize ketone bodies

Alcohol induced liver

damage

And if nothing else.