Biochemistry

Bioenergetics:How the body converts

food to energy

Bioenergetics

MetabolismMetabolism: The sum of all Chemical Reactions involved in maintaining the dynamic state of the cell– CatabolismCatabolism - breaking down of molecules to

supply energy– AnabolismAnabolism - synthesis of molecules– Biochemical Pathway Biochemical Pathway - a series of consecutive

chemical reactions

Common Catabolic Pathway

Conversion of FOOD to ATP:

FOOD produces C4 and C2 fragments

C4 and C2 fragments enter Citric Acid Cycle

CO2, NADH, FADH2, are produced

Electron Transport Electron Transport produces ATP

O2 O2

Citric AcidCycle

CC22

CC22

CC22

CO2

CO2

CO2

CC44CC44

NADH

FADH2

ATP

ATPATP

ATP

ATPH2O

outermembrane

innermembrane

e- tra

nspo

rt

e- tra

nspo

rt

Cells and Mitochondria

Components of a typical cell: nucleus - replication of cell begins here

lysosomes - remove damaged cellular components

Golgi bodies - package and transport proteins

organelles - specialized structures with specific function

mitochondria - common catabolic pathway

Cells and Mitochondria

Cells and Mitochondria

Mitochondria

MitochondriaMitochondria

– Two membranes

– Common Catabolic Pathway

– Enzymes located in folds or “CristaCrista”

– Transport thru the inner membrane occurs with

the help of Protein GatesProtein Gates

Mitochondrion

Common Catabolic Pathway

2 Parts: Citric Acid Cycle

– or Tricarboxylic Acid Cycle– or TCA cycle– or Kreb’s Cycle

Oxidative Phosphorylation– or Electron Transport– or Respiratory Chain

1

2

Compounds - ADP

Adenosine diphosphate (ADP)

adenosine diphosphate

CH2

OHOH

OO

N

N N

N

NH2

P

O

O-

OP

O

O-

O-

diphosphate

adenosine

adenine

ribose

Compounds - ATP

AMP, ADP, ATPHigh energy phosphate anhydride bonds

CH2

OHOH

OO

N

N N

N

NH2

P

O

O-

OP

O

O-

OP

O

O-

O-

triphosphate

Compounds - ATP

ATP– We make about 88 lbs. of ATP a day!!!– Used for:

» muscle contraction

» nerve signal conduction

» biosynthesis

CH2

OHOH

OO

N

N N

N

NH2

P

O

O-

OP

O

O-

OP

O

O-

O-

Fig. 26.6, p.651

Compounds - Redox

NAD+ and FAD– Oxidizing agents– Actually coenzymes– Contain an ADP core (part of R or R’)

N+

R

C NH2

O

NAD+

N

N

NC

NHC

H3C

H3C

O

R'

O

FAD

Compounds - Redox

NAD+ is converted to NADH

Oxidized form Reduced form

N+

R

C NH2

O

+ H+ + 2 e-NR

C NH2

OH H

to ET

Compounds - Redox

FAD is converted to FADH2

Oxidized form

Reduced form

N

N

NC

NHC

H3C

H3C

O

R'

O

+ 2 H+ + 2 e-

N

N

NC

NHC

H3C

H3C

O

R'

O

H

H

to ET

Compounds

The AcetylAcetyl carrying group - Acetyl coenzyme A Carrying handle is Pantothenic Acid and

Mercaptoethylamine

CCH3 S

O

CoA

acetyl CoA

Coenzyme A

CCH3 S

O

CoA

acetyl CoA

mercaptoethylamine

CH2

OHO3PO

OO

N

N N

N

NH2

P

O

O-

OP

O

O-

OC CH C CH2NH

O

CH2CH2C

O

OH CH3

CH3

CH2CH2 NHHS

pantothenic acid ADP

-

Coenzyme A

CCH3 S

O

CoA

acetyl CoA

mercaptoethylamine

CH2

OHO3PO

OO

N

N N

N

NH2

P

O

O-

OP

O

O-

OC CH C CH2NH

O

CH2CH2C

O

OH CH3

CH3

CH2CH2 NHHS

pantothenic acid ADP

-

4C4C3C3C2C2C

Fig. 26.8, p.652

http://www.youtube.com/watch?v=iXmw3fR8fh0

http://www.youtube.com/watch?v=lvoZ21P4JK8

http://www.youtube.com/watch?v=A1DjTM1qnPM

http://www.youtube.com/watch?v=FgXnH087JIk

Citric Acid Cycle

Acetyl CoA contains a 2 carbon fragment that is carried into the Citric Acid Cycle

Also called the:– Tricarboxylic Acid Cycle– TCA Cycle– Kreb’s Cycle

Acetyl group is split out as CO2

C5

CO2C4

C4 C6

CO2

C2

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Citric Acid Cycle

Step 1– oxaloacetate will show up in last step– acetyl CoA is the THIO ESTER of acetic acid (CoA

is Co Enzyme A)

CCH3 S-CoA

O

COO-

CH2

C

COO-

O

oxaloacetate acetyl CoA

+

citratesynthetase

citryl CoA

C

C

CH2

S-CoA

COO-

CH2

COO-HO

O

CCH3 S-CoA

O

COO-

CH2

C

COO-

O

oxaloacetate acetyl CoA

+

citratesynthetase

citryl CoA

C

C

CH2

S-CoA

COO-

CH2

COO-HO

O

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Citric Acid Cycle

Step 1B– citrate or citric acid produced– citrate has 6 C (How many acid groups?)

citryl CoA

C

CCH2

S-CoAO

COO-

CH2

COO-HO +H2O

citrate

C

CCH2

OO-

COO-

CH2

COO-HO + HS-CoA

citryl CoA

C

CCH2

S-CoAO

COO-

CH2

COO-HO +H2O

citrate

C

CCH2

OO-

COO-

CH2

COO-HO + HS-CoA

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Fig. 26.8, p.652

Citric Acid Cycle

Step 2– dehydration to cis-Aconitate– hydration to isocitrate– enzymes required for each Rx

citrate

C

CCH2

OO-

COO-

CH2

COO-HOaconitase

C

CCH2

OO-

COO-

CH

COO-

cis-aconitate

-H2O

aconitase

+ H2OC

CCH2

OO-

COO-

CH

COO-H

HO

isocitratecitrate

C

CCH2

OO-

COO-

CH2

COO-HOaconitase

C

CCH2

OO-

COO-

CH

COO-

cis-aconitate

-H2O

aconitase

+ H2OC

CCH2

OO-

COO-

CH

COO-H

HO

isocitrate

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Fig. 26.8, p.652

Citric Acid Cycle

Step 3– oxidation and decarboxylation

– CO2 is from the ???

C

CCH2

OO-

COO-

CH

COO-H

HO

isocitrate

isocitratedehydrogenase

-ketoglutarate

C

CCH2

OO-

COO-

C

H H

O

+ CO2

NAD+ NADH

C

CCH2

OO-

COO-

CH

COO-H

HO

isocitrate

isocitratedehydrogenase

-ketoglutarate

C

CCH2

OO-

COO-

C

H H

O

+ CO2

NAD+ NADH

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Fig. 26.8, p.652

Citric Acid Cycle

Step 4 – Where did the CO2 come from???

-ketoglutarate

C

CCH2

OO-

COO-

C

H H

O

enzymesystem

complex

C

CCH2

SCoA

C

H H

OO-

O

+ CO2

succinyl CoA

+ SCoA

NAD+ NADH

-ketoglutarate

C

CCH2

OO-

COO-

C

H H

O

enzymesystem

complex

C

CCH2

SCoA

C

H H

OO-

O

+ CO2

succinyl CoA

+ SCoA

NAD+ NADH

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Fig. 26.8, p.652

Citric Acid Cycle

Step 5– GTP is Guanosine triphosphate (as good as ATP!)

C

CCH2

SCoA

C

H H

OO-

O

succinyl CoA

+ GDP

enzymesystem

complex

C

CCH2

OO-

C

H H

OO-

succinate

+ GTP+ SCoA

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Fig. 26.8, p.652

Citric Acid Cycle

Step 6– Oxidation with FAD– Fumaric Acid is trans-Fumaric Acid – Barbiturate is an inhibitor of Succinate dehydrogenase

C

CCH2

OO-

C

H H

OO-

succinate

succinatedehydrogenase

C

CCH

OO-

C

H

OO-

fumarateFAD FADH2

C

CCH2

OO-

C

H H

OO-

succinate

succinatedehydrogenase

C

CCH

OO-

C

H

OO-

fumarateFAD FADH2

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Fig. 26.8, p.652

Citric Acid Cycle

Step 7– hydration reaction– fumarase is enzyme

C

CCH

OO-

C

H

OO-

fumarate

+ H2Ofumarase

CH2

CCH

OO-

C OO-

OH

malate

C

CCH

OO-

C

H

OO-

fumarate

+ H2Ofumarase

CH2

CCH

OO-

C OO-

OH

malate

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Citric Acid Cycle

Step 8– oxidation using NAD+

– product is oxaloacetate!

CH2

CCH

OO-

C OO-

OH

malate

malatedehydrogenase

CH2

CC

OO-

C OO-

O

oxaloacetateNADH NAD+

CH2

CCH

OO-

C OO-

OH

malate

malatedehydrogenase

CH2

CC

OO-

C OO-

O

oxaloacetateNADH NAD+

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Fig. 26.8, p.652

Electron (and H+) Transport

End products of the Citric Acid Cycle Reduced (or spent) Coenzymes

– NADH

– FADH2

Carry H+ and e- and yield energy when combining with oxygen:

4 H+ + 4 e- + O2 2 H2O4 H+ + 4 e- + O2 2 H2O

Electron (and H+) Transport

Many Enzymes are involved in ET Enzymes are imbedded in inner membrane of

the mitochondria Enzymes are in a particular sequence

– each accepts electrons– increasing affinity for electrons

Final acceptor of electrons is molecular O2 to make water O2

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Fig. 26.10, p.656

http://www.youtube.com/watch?v=xbJ0nbzt5Kw

http://www.youtube.com/watch?v=Idy2XAlZIVA

http://www.youtube.com/watch?v=A32CvcfA_K0&feature=PlayList&p=F09BC040A0B953F8&playnext=1&playnext_from=PL&index=10

http://www.youtube.com/watch?v=1engJR_XWVU

Electron Transport chain - youtube

Electron (and H+) Transport

Many Enzymes are involved in Oxidative Phosphorylation

2 H+ + 2 e- + 1/2 O2 H2O2 H+ + 2 e- + 1/2 O2 H2O

Flavo-protein

Lipid bilayerLipid bilayer

FeSprotein

Qenzyme

b

bc1 c a a3

ATPase

cytochromes

OO22

NADH NAD+ FADH2 FAD

ATPATP

2 H+ 2 H+ 2 H+

overall 2 ATP2 ATPproduced

overall 3 ATP3 ATPproduced

O2-

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The Energy Yield from a C2

Each NADH produces 3 ATP Each FADH2 produces 2 ATP

(Each pair of H+ produces 1 ATP)

For each C2 unit (acetyl CoA) we produce...– 1 GTP directly (same as 1 ATP) from step 5 TCA

– 3 NADH in ET (3 x 3 = 9 ATP) Indirect

– 1 FADH2 in ET (1 x 2 = 2 ATP) Indirect

For a total of ..................... 12 ATP(and some waste CO2)

$

Indirect(from ET)

Conversion of ATP

How does the body utilize this Chemical Energy? Conversion to Other Forms

– biosynthesis Electrical Energy

– ion gradients (K+, Na+) Mechanical Energy

– muscle contraction Heat Energy

– maintain 37 oC or 98.6 oF

Muscle Contraction

Chemical Energy converted to Mechanical Energy:

Thick (myosin) and thin (actin) filaments Hydrolysis of ATP causes the interaction of the

filaments (muscle contraction)

contraction