Introduction to Metabolism

Metabolism
(The Acquisition and Utilization of Free Energy)

Catabolism: exergonic oxidation Anabolism: endergonic processes

(Biosynthesis) (Endergonic)

(Exergonic) (Oxidation)

Function of ATP
Cells make use of ATP for:

Chemical work ATP supplies energy to synthesize macromolecules, and therefore the organism Transport work ATP supplies energy needed to pump substances across the plasma membrane Mechanical work ATP supplies energy for cellular movements

Redox Reactions

NAD (Nicotinamide Adenine Dinucleotide)

Electron transfer from NADH provides free energy (NAD+/NADH)
H O C + N R N + AD N2 H
+ e +H 2

O C N2 H

N R N DH A

The electron transfer reaction: NAD+ + 2e + H+ NADH. It may also be written as: NAD+ + 2e + 2H+ NADH + H+

FAD (Flavin Adenine Dinucleotide)

d e ysaoai e i t l ol x n O m i l z h
H C C 3 H C C 3 H C C C N C C C N H
O C C C N H CO

2 + HH e 2 C
3

H C

C C

H N

C H

CO

H C C 3

C H 2 H O C H

C H

C H 2

N H

H O C H

FD A

H O C H H OO C H O A ne di en

FD A 2 H

H O C H H OO C H O A ne di en

H C OP OP ORs io be 2 O O -

H C OP OP ORs io be 2 O O -

FAD accepts 2 e + 2 H+ in going to its reduced state: FAD + 2 e + 2 H+ FADH2

Metabolic Networks
Reactions: Pathways: Networks:
A B

Metabolic Pathways

A > B

Metabolic Pathways

A > B > C > D > E

Metabolic Pathways

A > B > C > D > E

F > G > H

Metabolic Pathways

A > B > C > D > E

e5
e6 e7

e1

e2

e3

e4

F > G > H

Metabolic Pathways

A > B > C > D > E

e5
e6 e7

e1

e2

e3

e4

F > G > H

Metabolic Pathways
S

A > B > C > D > E

e5
e6 e7

e1

e2

e3

e4

F > G > H
Cell membrane

Properties of Metabolic Pathways

Irreversible (overall): reversibility of individual steps Separate Anabolic and Catabolic Pathways First Committed (Exergonic) Step: others close to equilibrium Regulation (usually first committed step): often rate-limiting Compartamentation: transport

Control of Metabolic Pathways

Feedback inhibition Enzyme modulators No enzyme Enzyme isolation Energy availability - ATP

Example of Metabolic Regulation

A Summary of the Pathways of Catabolism and Anabolism

Catabolism: The Breakdown of Macro-nutrients

Energy Production ATP

Glycolysis
Phosphorylation Pyruvate
Anaerobic respiration Lactate production 2 ATPs produced

Overview of aerobic pathways for ATP Production

Glycolysis
Event 1 - Phosphorylation two phosphates added to glucose requires ATP

Event 2 Splitting (cleavage) 6-carbon glucose split into two 3-carbon molecules
4-14

Glycolysis
Event 3 Production of NADH and ATP hydrogen atoms are released hydrogen atoms bind to NAD+ to produce NADH NADH delivers hydrogen atoms to electron transport chain if oxygen is available ADP is phosphorylated to become ATP two molecules of pyruvic acid are produced
4-15

Glycolysis Summary
Inputs: Glucose 2 NAD+ 2 ATP 4 ADP + 2 P Outputs: 2 pyruvate 2 NADH 4 ADP 2 ATP (net gain)

Anaerobic Reactions
If oxygen is not available electron transport chain cannot accept NADH pyruvic acid is converted to lactic acid glycolysis is inhibited ATP production declines
4-16

Fermentation
In the absence of oxygen, the end-product of glycolysis, pyruvate, is used in fermentation.
During glycolysis, all the NAD+ becomes saturated with electrons (NADH). When this happens, glycolysis will stop.
2 NADH and 2 ATP produced.

Pyruvate is used as the electron acceptor resetting the NAD+ for use in glycolysis.

Fermentation 2 Types
Animals add extracted electrons to pyruvate forming lactate.
Reversible when oxygen becomes available. Muscle fatigue

Yeasts, single-celled fungi, produce ethanol.

Present in wine & beer. Alcoholic fermentation

Pyruvate

fermentation
Escherichia Enterobacter
Lactobacillus

Saccharomyces Propioni-bacterium

Clostridium

Ethanol + lactate + acetate + succinate + carbon dioxide + hydrogen + formate

Ethanol + 2,3-butanediol + formate + lactate + carbon dioxide + hydrogen

Lacta te

Ethanol + carbon dioxide

Propiona te + carbon dioxide + hydrogen + acetate

Butyrate + butanol + isopropanol + acetone + carbon dioxide

31

Glycolysis takes place in the cytoplasm of almost all cells.

Aerobic Reactions
If oxygen is available pyruvic acid is used to produce acetyl CoA

citric acid cycle begins

electron transport chain functions

carbon dioxide and water are formed

36 molecules of ATP produced per glucose molecule
4-17

Citric Acid Cycle

Citric acid cycle

Citric acid cycle inputs and outputs per glucose molecule

Inputs: 2 acetyl groups 6 NAD+ 2 FAD 2 ADP + 2 P Outputs: 4 CO2 6 NADH 2 FADH2 2 ATP

Aerobic Respiration
In aerobic respiration, ATP forms as electrons are harvested, transferred along the electron transport chain and eventually donated to O2 gas.
Oxygen is required! Glucose is completely oxidized. C6H12O6 + 6O2 6CO2 + 6H2O + energy
Glucose Oxygen Carbon Dioxide Water

(heat or ATP)

Cellular Respiration - 3 Stages

Food is digested to break it into smaller
pieces no energy production here. Glycolysis coupled reactions used to make ATP. Occurs in cytoplasm Doesnt require O2 Oxidation harvests electrons and uses their energy to power ATP production. Only in mitochondria More powerful

Mitochondria Inner Structure

Organization of cristae

Using Electrons to Make ATP

NADH & FADH2 contain energized electrons. NADH molecules carry their electrons to the inner mitochondrial membrane where they transfer electrons to a series of membrane bound proteins the electron transport chain.

Producing ATP- Chemiosmosis

A strong gradient with many protons outside the matrix and few inside is set up. Protons are driven back into the matrix. They must pass through special channels that will drive synthesis of ATP. Oxidative phosphorylation

Energy Yield from Glucose Metabolism

Per glucose molecule, there is a net gain of two ATP from glycolysis, which occurs in the cytoplasm by substrate-level phosphorylation. The citric acid cycle, occurring in the matrix of mitochondria, adds six more ATP, also by substrate-level phosphorylation.

Energy Yield from Glucose Metabolism

Most ATP is produced by the electron transport system and chemiosmosis. Per glucose molecule, ten NADH and two FADH2 take electrons to the electron transport system; three ATP are formed per NADH and two ATP per FADH2. Electrons carried by NADH produced during glycolysis are shuttled to the electron transport chain by an organic molecule.

Accounting of energy yield per glucose molecule breakdown

Glucose + 2 ATP + 36 ADP + 36 Pi + 6 O2

6CO2 + 2 ADP + 36 ATP + 6 H2O

Metabolism of Lipids
Triglycerides are broken down into glycerol and 3 fatty acid chains. Glycerol enters glycolysis. Fatty acids are oxidized and 2-C molecules break off as acetyl-CoA.
Oxidation of one 18-C stearic acid will net 146 ATP. Oxidation of three glucose (18 Cs) nets 108 ATP. Glycerol nets 22 ATP, so 1 triglyceride nets 462 ATP.

Metabolism of Proteins
Proteins digested in the gut into amino acids which are then absorbed into blood and extracellular fluid. Excess proteins can serve as fuel like carbohydrates and fats.
Nitrogen is removed producing carbon skeletons and ammonia.
Carbon skeletons oxidized.

Metabolism of Proteins
Ammonia is highly toxic, but soluble.
Can be excreted by aquatic organisms as ammonia.

Terrestrial organisms must detoxify it first.

Synthetic (Anabolic) pathways

Glycogen synthesis
Liver storage Glucose to glycogen

Gluconeogenesis
Amino acids Glycerol Lactate
Figure 4-29: Gluconeogenesis

Lipogenesis

Lipid synthesis

Lipid Synthesis

Introduction to Metabolism

Alfonse, Biochemistry makes my head hurt!! \