Introduction to Introduction to MetabolismMetabolism

What is energy?• the ability to do work – carry out life functions

Energy is used to:• Break down larger compounds (catabolism)

+• Build complex substances (anabolism)

______________

metabolism

Types of EnergyTypes of Energy

Plants use solar (light ) energy Glucose bonds store chemical potential

energy Moving objects possess kinetic energy Living organisms release thermal (heat)

energy

Laws of ThermodynamicsHow energy flows between organisms is

governed by the Laws of Thermodynamics

1st law of Thermodynamics – energy

cannot be created or destroyed. It can only

be converted from one form to another.

Example: photosynthesis: plants absorb

solar energy chemical potential energy

(in bonds of a sugar molecule)

When energy transformations occur, some

energy is lost as heat and is not available to do

work (not free energy).

When energy is lost, we say the entropy

(disorder) is increasing

2nd law of thermodynamics – all energy transformations increase the entropy of the universe

Introduction to Metabolism - Introduction to Metabolism - continuedcontinued

Most of our available energy is stored as chemical potentialenergy in the covalent bonds of the food we eat.Main source of energy:

Glucose – C6H12O6

C6H12O6 + O2 CO2 + H2O + Energy

When the bonds in a glucose molecule are broken, and atomsare rearranged to form products - energy is released. Some of this energy becomes available to do work (called Gibbs freeenergy). Some energy is lost as heat. The change is free energy represented as ΔG.

energy

Oxidation of glucose:ΔG = - 2870 kJ/mol

Why a negative value?ΔG = G final – G initial

The negative sign shows that the products haveless chemical potential energy (i.e stronger bonds,more stable) than the reactants.

This means:The energy released when the products form is greater than theenergy absorbed when the reactants’ bonds broke. Some of

thisdifference in energy is now available or “free” to do work – move, produce light, sound. Some is lost as heat. Reactions

thatrelease energy are called Exergonic. Catabolic reactions areexergonic.

Compare to photosynthesis:

Energy + CO2 + H2O C6H12O6 + O2

ΔG = 2870 kJ/mol

The products have more chemical potential energy

energy. There has to be an investment of energy to

make this reaction possible. The energy came

from the sun.

Reactions that require energy to be absorbed

before they proceed are called Endergonic

reactions. Anabolic reactions are endergonic.

The controlled stepwise oxidation of sugar that occurs in the cell preserves useful energy, unlike

the simple burning of the same fuel molecule. In the cell, enzymes catalyze oxidation via a series of small

steps in which free energy is transferred in conveniently sized packets to carrier molecules — most often ATP

and NADH. At each step, an enzyme controls the reaction by reducing the activation energy barrier that has to

be surmounted before the specific reaction can occur. The total free energy released is exactly the same in (A)

and (B).  

Balanced equation:C6H12O6 + 6O2 6CO2 + 6H2O + 36 ATP

Thousands of chemical reactions just occurred in your body. Some required energy (anabolic). From where did this energy come?

ATP – adenosine triphosphate

ATP is a universal molecule of energy transfer –

like a cell’s currency.

Any energy made available by some cellular

process (ex: cell respiration) is first transferred

to ATP. If that energy is needed later, it is released

by ATP

ATP –Structure & SynthesisATP –Structure & Synthesis

ribose

O

A Adenine

ATP + H2O ADP + Pi + Energy

- the high energy phosphate bonds (~) are very unstable & can be easily hydrolyzed (by adding H2O)

∆ G = - 31 kJ/mol exergonic (energy released) – available to

do work (free energy)

Energy + ADP + Pi ATP + H2O ∆ G = 31 kJ/mol endergonic

(energy taken in)

PPP

Inorganic phosphate

The process by which ATP is synthesized(from ADP) and broken down (to ADP) is thebasis of cell metabolism. ADP and ATP areshuttled throughout your cells to:a) Provide energy for endergonic reactions like

building macromolecules, contracting musclesb) Store the energy released when exergonic

reactions occur (ex: glucose broken down)

Note: When ADP binds a Pi, ATP is made. This reaction is catalyzed by an enzyme. ATP made in this manner is called substrate-level phosphorylation. The addition of a Pi group to any molecule is termed phosphorylation.

The Release of Energy in the Cell

Recall: the explosive burning (oxidation) of glucose

How do you convert the great deal of free energy in

glucose into the small more easily managed energy

molecules called ATP?

Need the help of:• Enzymes • Coenzymes – not proteins, much smaller, assist enzymes, act

as electron carriers – involved in redox reactions. Include:

NAD+ – nicotinamide adenine dinucleotide

NADP - nicotinamide adenine dinucleotide phosphate

FAD – flavin adenine dinucleotide

The transfer of glucose energy to ATP The transfer of glucose energy to ATP can be accomplished by:can be accomplished by:

i) aerobic respiration a) glycolysis

b) kreb’s cycle

c) electron transport system

ii) Anaerobic respiration- a) ethanol fermentation b) lactic acid

fermentationBoth aerobic and anaerobic respiration begin with the same set of reactions called glycolysis – “sugar splitting”

- occurs in the cytoplasm - No oxygen is required

- involves 9 enzyme mediated reactions

GlycolysisGlycolysis – – occurs in cytoplasmoccurs in cytoplasm glucose

outside cell membrane

ATP ADP Hexokinase – breaks down ATP and 1 Pi attaches to

glucose (phosphorylation of glucose) & ADP is released Glucose – 6 – phosphate Phosphoglucoisomerase – takes molecule and rearranges it into a fructose

Fructose – 6 – phosphate

ATP ADP

Phosphofructokinase (PFK) – takes Pi from ATP and attaches it; ADP is release

- it is the rate limiting step aka the flux generating step Fructose – 1, 6 - bisphosphate

PGAL (phosphoglyceraldehyde) -aka glyceraldehyde 3-phosphate (G3P)

Aldolase – splits molecule in 2

PGAL (phosphoglyceraldehyde)

NAD+

Pi NADH +H+ Phosphate dehydrogenase – Pi (present in

cytoplasm) attaches to PGAL , 2H+ & 2 e- are taken away (from PGAL) and given to NAD+ to make NADH + H+ 1, 3 - bisphosphoglycerate

ATP ADP Phosphoglycerokinase – 1 Pi group removed and added to ADP to form ATP (substrate level phosphorylation)3 - phosphoglycerate

Phosphoglyceromutase – changes location of Pi group onto 2nd C so it is more balanced

2 - phosphoglycerate

H2O Enolase – takes out H2O and makes molecule

symmetrical PEP (phosphophenol pyruvic acid)

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PEP (phosphophenol pyruvic acid)

ATP ADP

Pyruvate kinase – P group removed and joined with ADP to make ATP (substrate level phosphorylation)

pyruvate

w/ O2 – aerobic

respiration in Kreb’s Cycle

w/out O2 – fermentation

2 ATP net gain2 NADH + 2 H+

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Net Glycolytic EquationNet Glycolytic Equation C6H12O6 + 2 ATP + 2NAD+ 2 PYRUVATE + 4 ATP + 2 NADH + 2 H2O

there is a net gain of 2 ATP from glycolysis

recall: glucose = – 2870 kJ/mol (total possible released)

glycolysis = 2 x ( – 31 kJ/mol) (1 ATP = – 31 kJ/mol)

= – 62 kJ/mol

efficiency = – 62 kJ/mol x 100% – 2870 kJ/mol

= 2% there is only 2% of the possible energy released by glycolysis

glycolysis is extremely inefficient @ harvesting energy - very small cells, like yeast, bacteria can live like this but our cells

cannot ...if O2 is present, the pyruvate enters the inner Matrix of the

mitochondria for the Krebs cycle & ETS

Structure of Mitochondrion (pl: mitochondria)

Decarboxylation – CO2 removed from pyruvate

Preparatory stage (aka Transition Stage)

Multiply all products by 2. Why?

Krebs Cycle Krebs Cycle

(aka Citric Acid Cycle)(aka Citric Acid Cycle)

oxaloacetate

citrate

isocitrate

H2OH2O

- ketoglutarate

CO2

NAD+

NADH + H+

Succinyl – CoA

Coenzyme A

CO2

NAD+ATP

succinate

fumarate

malate

FAD

FADH2

NADH + H+

NAD+

H2O

GTP (guanosine triphosphate)

GDP

Pi + ADP

Pi +

CoAAcetyl – CoA

NADH + H+

Coenzyme A

Net products:6 NADH2 ATP2 FADH2

4 CO2 x 2 everything

FMN Qcyt b

cyt c1

cyt c

cyt a

cyt a3

Protonpump

pumpP

roton pump

ATPase

Proton

INNER MATRIX

Inner mitochon-drial membrane

FADH2 FAD

H+

NADH NAD+

e- e-

H+

H+H+

H+

H+

H+

ATP ADP + Pi

H+H+

H+

H+

H+

H+H+

H+ H+H+H+ H+ H+

H+

( - )

( + )

energ

y give

n toto make

O2

O O

2e-

O2e + 2H+

H2O

Space b/w inner & outer m/b

Kreb cycle

(6 NADH, 2 FADH2, 2 ATP)

ETS

So, how many ATP are made?

For every H+ ion that is pumped out, 1 re-enters andthe energy it releases (as it moves down theelectrochemical gradient) is used to make 1 ATP

So, 34 H+ pumped out, 34 re-enter = 34 ATP made by ETC

34 ATP + 2 ATP + 2 ATP = 38 ATP ETS glycolysis Kreb’s

Efficiency of aerobic respiration : 38 x (31kJ/mol) ÷ 2870 kJ/mol =

41%

Note: One small problem- the 2 NADHs produced in glycolysis (in the cytoplasm) must be brought into the mitochondrion at a cost of some energy, usually estimated to be 1 ATP per NADH. So, final ATP count is 36.

How many O2 molecules are required as the final electron acceptors (for each

glucose molecule)?10 NADH pass on 2e- each 20 e-

2 FADH2 pass on 2e- each 4 e-

Each oxygen atom has room for 2 electrons in outer shell

2 6

O2 = 2 oxygen atoms, each accept 2e- = 4e-

24e- ÷ 4e-(per O2 molecule) = 6O2

Recall: Oxygen atom accepts 2e-, 6O2 + 24e- + 24 H+ = 12 H2O molecules

6 H2O molecules get used up in previous reactions, net gain of 6H2O

Alleluia, alleluia, Alleluia, alleluia, alleluia……….alleluia……….

Overall equation for cell respiration (aerobic

respiration), the process by which the energy

stored in glucose is released and stored in

ATP is:

C6H12O6 + O2 6CO2 + 6H2O + 36 ATP

Why is this chemical equation somewhat deceiving?

Cell Respiration song

http://www.youtube.com/watch?v=3aZrkdzrd04

FermentationFermentation Recall: NAD functions in the cell as an energy transport compound. The cell has a limited supply of this compound. In glycolysis, 2 molecules of NAD+ are reduced to NADH + H+. Under aerobic conditions, the NADH transfer their H and 2e- to the ETC (where O2 is the final electron acceptor). But, without O2, how would NADH unload the electrons it picked up? If NADH doesn’t get oxidized the cell’s supply of NAD+ would run out. The result …… glycolysis would stop (no NAD+ as a reactant) and the cell would die from lack of ATP. All single celled organisms (like bacteria) that can currently live in areas without oxygen (anaerobic) would cease to exist.So...how to keep glycolysis going? NADH must find another acceptor for H & its electron(s). That acceptor is……

….Pyruvate.

The process that enables a cell to continue synthesizing

ATP by the breakdown of glucose under anaerobicconditions is FERMENTATION.

2 types:1. Lactic Acid (lactate) fermentation2. Ethanol Fermentation (aka alcoholic

fermentation)

Lactic Acid (lactate) FermentationLactic Acid (lactate) Fermentation

• Occurs in fungi (cheese making), bacteria (in yogurt) and muscles depleted of O2

• pyruvate becomes the acceptor of H atoms and e- from NADH. NAD+ is shuttled back to the glycolytic pathways so ATP can continue to be made (rate ↑). Pyruvate becomes lactate

• Enzyme LDH – lactate dehydrogenase mediates this process.

• During strenuous exercise, muscles cells have greater demand for ATP, not enough O2. Lactic acid produced – causes muscle soreness

• O2 debt “paid back” by deep breathing

• Lactic acid removed to the liver and converted to glucose

Ethanol FermentationEthanol Fermentation

• Involve yeast – single celled fungi

• Occurs in bread making (CO2 forms bubbles in dough and alcohol evaporates during baking) beer, wine, champagne (CO2 does not escape)

• CO2 is removed from pyruvate to become acetaldehyde, then acetaldehyde accepts H to become ethanol (aka ethyl alcohol, grain alcohol)

• Final products= ethanol + CO2

Other Fuel SourcesOther Fuel Sources