Cellstructure& Genetic Control

Bioenergetics and Glycolysis

Getting the E out of C

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Energy Transfer follows thermodynamic laws

• Gibbs helmholtz– ΔG = ΔH – TΔS

• Enthalpy• Entropy

– Remember ΔSuniverse > 0 is a spontaneous process

• Overall if ΔG < 0 the process is spontaneous• ΔG = -RTlnK

– Relates ΔG to equilibrium• ΔG are additive

• State function• Overall ΔG has to be – for a process to be spontaneous


Le Chatelier’s Principle and ΔG

• Remember Le Chatelier and affect on equilibrium– If one reaction has a positive ΔG, but the next

reaction, which is in equilibrium has a negative ΔG , the first reaction can be pulled through

– Many examples of this in glycolysis


ATP (Adenosine Tri-Phosphate)

OH P O

O

O

P OO

O

P O

O

O

N

O

N

N

OH

OH

N

NH2


Hydrolysis of ATP

OH P O

O

O

P OO

O

P O

O

O

N

O

N

N

OH

OH

N

NH2

OH P OO

O

P O

O

O

N

O

N

N

OH

OH

N

NH2

O P O

O

O

+

ATP ------ ADP + Pi + 7.3 kcal


Energy from ATP hydrolysis

• 7.3 kcal /mol (30.5 kJ/mol for you SI nuts)

• Energy from:– Separation of negative charges– Increased entropy

• Phosphate now free…2 thing instead of one

– Resonance stabilization of phosphate


Other Energy sources

• Hydrolysis of thioester– Resonance

stabilization of carboxylate

– Energy released from group transfer, not simply hydrolysis

– Coenzyme A (CoA) is an important thiol that forms thioesters

R S

O

R'R

O

O SHR

+


Coenzyme A

OP O

O

OO P O

O

O

P O

O

O

N

O

N

N

OH

N

NH2

CC

CH3

CH3H

OH

CN

O

H

CH2CH2C

O

NCH2CH2

H

SH

from pantothenic acid(Vitamin B5)

from beta alanine


Redox

• Review:– Electron transfer reactions– Energy from electron transfer– ΔG = -nFE– Electrons typically transferred to a carrier

• NAD+ + 2 e- + 2H+ - NADH + H+

• FAD + 2 e- + 2H+ - FADH2

• Electrons transferred later for ATP generation


NAD (Nicotinamide Adenine Dinucleotide)

O

P

O

O

O

P

O

O

O

N

O

N

N

OH

OH

N

NH2

N+

OHOH

O

H

NH2

O


Reduction of NAD+ on Nicotinamide Ring

N+

H

NH2

O

R

2 H+2 e -

N

H

NH2

OH

R

H+

NADHNAD

+ ++


FAD (Flavin Adenine Dinucleotide)

CH2

OHOH

OH

N

N

N

NCH3

CH3

O

O

H

CH2

O

OP O

O

ON

O

N

N

OH

OH

N

NH2O P O


Reduction of Flavin Ring on FAD

N

N

N

NCH3

CH3

O

O

H

R

2 H+2 e-

N

N

N

NCH3

CH3

O

O

H

H

H

R

FADFADH2

+ +


Glycolysis

• In Cytosol

• Anaerobic

• Breakdown of glucose to two pyruvate molecules

– Glucose + 2 ADP + 2 Pi + 2 NAD+ - 2 pyruvate + 2 ATP + 2 NADH + 2 H+

– C6H12O6 + 2 ADP + 2 Pi + 2 NAD+ - 2 C3H3O3- + 2 ATP + 2 NADH + 2 H+


Glycolysis

O

OHOH

OH

OH

CH2OH

glucose

ATP ADP

O

OHOH

OH

OH

CH2OP

Glucose-6-phosphate

hexokinasehexose phosphate isomerase

O

CH2OPCH2OH

OH

OH

OH

fructose-6-phosphate

ATP

ADP

O

CH2OP CH2OP

OH

OH

OHfructose-1,6-bisphosphate

phosphofructokinase

aldolase

CH2OH

C

CH2OP

Odihydroxy acetone phosphate

CC

CH2OP

OHH

HO

glyceraldehyde-3-phosphate

NAD+NADHPi

CC

CH2OP

OHH

OPO

1,3-diphosphoglycerate

glyceraldehyde - phosphate dehydrogenase

ADPATP

CC

CH2OP

OHH

OO

phosphoglycerate kinase

3-phosphoglycerate

CC

CH2OH

OPH

OO

phosphoglycerate mutase

2-phosphoglycerate

OH2

phosphoenolpyruvateenolase

CC

CH2

OP

OO ADP ATP

C

C

CH3

O

OO

pyruvate kinase

pyruvatewww.freelivedoctor.com

Hexokinase reaction

O

OHOH

OH

OH

CH2OH

glucose

ATP ADP

O

OHOH

OH

OH

CH2OP

Glucose-6-phosphate

hexokinase

• Irreversible• Kinase (phosphate transfer)• -16.7kJ


Hexose phosphate isomerase reaction

O

OHOH

OH

OH

CH2OP

Glucose-6-phosphate

hexose phosphate isomerase

O

CH2OPCH2OH

OH

OH

OH

fructose-6-phosphate

• Keto-aldol isomerization – Glucose to fructose

• 1.7 kJ


Phosphofructokinase reaction

O

CH2OPCH2OH

OH

OH

OH

ATPADP

O

CH2OP CH2OP

OH

OH

OHfructose-1,6-bisphosphatephosphofructokinase

• Same as hexokinase reaction• -14.2kJ• Major point of regulation

– Committed step– Stimulated by ADP and AMP– Inhibited by ATP and fatty acids


Aldolase Reaction

O

CH2OP CH2OP

OH

OH

OHfructose-1,6-bisphosphate

aldolase

CH2OH

C

CH2OP

O

dihydroxy acetone phosphate

CC

CH2OP

OHH

HO


+

• Reverse aldol condensation• 23.8kJ• Makes 2 3-Carbon molecules


Triose phosphate isomerase

CH2OH

C

CH2OP

O

dihydroxy acetone phosphate

CC

CH2OP

OHH

HO


triose phosphate isomerase

• Keto-enol isomerization (like hexose phosphate isomerase reaction)

• 7.5kJ• Net is 2 glyceraldehyde – 3 – phosphate• From now on each reaction times 2


Glyceraldehyde -3-phosphate dehydrogenase

CC

CH2OP

OHH

HO


NADH

CC

CH2OP

OHH

OPO


glyceraldehyde - phosphate dehydrogenase

NADPi

• Oxidation coupled to phosphorylation• Makes NADH• 6.3kJ• (remember X 2)


Phosphoglycerate Kinase

CC

CH2OP

OHH

OPO


ADP ATPCC

CH2OP

OHH

OO

phosphoglycerate kinase3-phosphoglycerate

• Phosphate transfer– Substrate level phosphorylation

• Driven by stabilization of carboxylate• -18.5kJ• Pulls previous reactions through


Phosphoglycerate mutase

CC

CH2OP

OHH

OO

3-phosphoglycerate

CC

CH2OH

OPH

OO

phosphoglycerate mutase

2-phosphoglycerate

• Moves from 3 - 2• 2 steps

– Makes 2,3– Removes 3

• 4.4kJ


enolase

CC

CH2OH

OPH

OO

2-phosphoglycerate

OH2

phosphoenolpyruvateenolase

CC

CH2

OP

OO

• Makes unstable enol intermediate• 7.5 kJ


Pyruvate kinase

phosphoenolpyruvate

CC

CH2

OP

OO ADP ATP

C

C

CH3

O

OO

pyruvate kinase

pyruvate

• Last reaction….woohoo• Substrate level phosphorylation• Stabilization of enol - keto• -31.4kJ


Net products from Glycolysis (per glucose)

• 2 pyruvate

• 2 NADH

• 2 ATP

• Total energy = -61.3 kJ– Sum of energies


Fates of pyruvate

CH3

O

O

O

CH3 OH CH3

OH

O

O

ethanolpyruvate

lactate

NAD+NAD+

NADH NADHCO2

CO2

HSCoA

CH3 SCoA

O

acetyl CoA

lactate dehydrogenase (LDH)pyruvate decarboxylase

pyruvate dehydrogenase

NADH

NAD+


Fates of Pyruvate

• Depend on organism and conditions• Yeast

– Anaerobic• Pyruvate decarboxylase• Makes alcohol

– Aerobic• Makes acetyl CoA --- energy or fat

• Others– Anaerobic

• LDH• Makes lactate• Sore muscles

– Aerobic• Acetyl Co A --- energy or fat


Glycogen

O

OOH

OH

OH

CH2OH

O

OH

OH

CH2OH

O

CH2

O

OOH

OHO

CH2OH

O

OHOH

OH

CH2OH

O

OH

OH

O

O

OH

OH

OH

CH2OH


Glycogenolysis


Glycogen breakdown

• Glycogen phosphorylase breaks down alpha 1,4 linkages– Makes glucose-1-phosphate– Enzyme changes to glucose-6-phosphate and enters

glycolysis there

• Can’t break 1,6 linkages– Debranching enzyme breaks 1,6 (when 4 sugars

away from branch) and adds to end– Glycogen phosphorylase takes over and breaks down

the rest


Other sugars

• Fructose– Comes in at fructose-6-p and immediately

phosphorylated• Lipogenic…after branch to glycogen…makes

acetyl CoA

• Lactose– Glucose and galactose

• Galactose– Epimerase turns into glucose-6-P and enters there


gluconeogenesis

• Making glucose from pyruvate– In liver– Uses same enzymes as glycolysis except

where nonequilibrium reactions– Uses NADPH instead of NADH


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