Transcript Camp 1 - Chemistry notes

Frederick A. Bettelheim
William H. Brown
Mary K. Campbell
Shawn O. Farrell
www.cengage.com/chemistry/bettelheim
Chapter 27
Bioenergetics; How the Body
Converts Food to Energy
William H. Brown • Beloit College
Metabolism
Metabolism: The sum of all chemical reactions involved in
maintaining the dynamic state of a cell or organism.
• Pathway: A series of biochemical reactions.
• Catabolism: The process of breaking down large
nutrient molecules into smaller molecules with the
concurrent production of energy.
• Anabolism: The process of synthesizing larger
molecules from smaller ones.
27-2
Metabolism
Metabolism is the sum of catabolism and anabolism.
C ataboli s m
Polys acTri glyce ri des ch ari de s
An abol is m
Prote in s
be ak down
of larger
Fatty aci ds Mon os ac- Ami n o
mol ecu l es
an d glyce rol ch ari de s
Acids
to sm all er
on e s
S mal l
An abol is m
mol ecu l es of protei n s
oxidati on an d th e
rel e ase of e n e rgy
Excre ti on An abol is m
C ataboli s m
Excre ti on
Produ cts of an abol is m,
i ncl u di n g prote in s an d
n u cle ic acids
e n e rgy an d
redu cin g
agen ts
S ome n u tri e n ts an d
produ cts of catabol i sm
27-3
Cells and Mitochondria
Animal cells have many components, each with specific functions;
some components along with one or more of their functions are:
• Nucleus: Where replication of DNA takes place.
• Lysosomes: Remove damaged cellular components and some
unwanted foreign materials.
• Golgi bodies: Package and process proteins for secretion and
delivery to other cellular components.
• Mitochondria: Organelles in which the common catabolic pathway
takes place in higher organisms; the purpose of this catabolic
pathway is to convert the energy stored in food molecules into
energy stored in molecules of ATP.
27-4
A Rat Liver Cell
Figure 27.2
Diagram of a
rat liver cell,
a typical
higher animal
cell.
27-5
A Mitochondrion
• Figure 27.3 Schematic of a mitochondrion cut to reveal
the internal organization.
27-6
The Common Metabolic Pathway
•
The two parts to the common catabolic pathway:
• The citric acid cycle, also called the tricarboxylic acid (TCA)
or Krebs cycle.
• Electron transport chain and phosphorylation, together
called oxidative phosphorylation.
• Four principal compounds participating in the common
catabolic pathway are:
• AMP, ADP, and ATP: agents for the storage and transfer of
phosphate groups.
• NAD+/NADH: agents for the transfer of electrons in
biological oxidation-reduction reactions
• FAD/FADH2: agents for the transfer of electrons in biological
oxidation-reduction reactions
• Coenzyme A; abbreviated CoA or CoA-SH: An agent for the
transfer of acetyl groups.
27-7
Adenosine Triphosphate (ATP)
ATP is the most important compound involved in the
transfer of phosphate groups.
• ATP contains two phosphoric anhydride bonds and
one phosphoric ester bond.
ph os phoric
ester
NH2
O O O
O-P-O-P-O-P-O-CH2
O
O O O
H
H
H
ph os phoric
anh yd rides
HO
N
N
N
aden ine
N
 -N -glycos idic b on d
H
OH -D-ribofuranose
27-8
Adenosine Triphosphate (ATP)
• Hydrolysis of the terminal phosphate (anhydride) of
ATP gives ADP, phosphate ion, and energy.
O O
O-P-O-P-O-AMP + H2 O
O O
ATP
O
O-P-O-AMP + H2 PO4 + 7.3 kcal/mol
O
AD P
• Hydrolysis of a phosphoric anhydride liberates more
energy than hydrolysis of a phosphoric ester.
• We say that ATP and ADP each contain high-energy
phosphoric anhydride bonds.
• ATP is a universal carrier of phosphate groups.
• ATP is also a common currency for the storage and
transfer of energy.
27-9
NAD+/NADH
• Nicotinamide adenine dinucleotide (NAD+) is a biological
oxidizing agent.
The p lus sign on N A D +
represents th e positive
ch arge on this n itrogen
O
CNH2
O
-
O-P-O-CH2
O
AMP H
N+
O
H
H
H
HO
N icotinamide;
derived
from niacin
a -N-glycosidic
bond
OH
27-10
NAD+/NADH
• NAD+ is a two-electron oxidizing agent, and is reduced
to NADH.
• NADH is a two-electron reducing agent, and is oxidized
to NAD+. The structures shown here are the
nicotinamide portions of NAD+ and NADH.
H
O
C
NH2 + H+ + 2 e-
H H O
C
NH2
:
N
Ad
NAD+
(oxidized form)
N
Ad
N AD H
(reduced form)
• NADH is an electron and hydrogen ion transporting
molecule.
27-11
FAD/FADH2
• Flavin adenine dinucleotide (FAD) is also a biological
oxidizing agent.
O
Riboflavin
H3 C
N
H3 C
N
N
N
H
Flavin
O
CH2
H C OH
H C OH
Ribitol
H C OH
CH2
O
O=P-O-AMP
O-
27-12
FAD/FADH2
• FAD is a two-electron oxidizing agent, and is reduced
to FADH2.
• FADH2 is a two-electron reducing agent, and is oxidized
to FAD.
• Only the flavin moiety is shown in the structures below.
O
H3 C
H3 C
N
N
N
Ad
FAD
NH
O
H3 C
H
N
O
NH
+ 2 H+ + 2 e H3 C
N
N
Ad H
O
FAD H2
27-13
Coenzyme A
• Coenzyme A (CoA) is an acetyl-carrying group.
• Like NAD+ and FAD, coenzyme A contains a unit of
ADP
• CoA is often written CoA-SH to emphasize the fact that
it contains a sulfhydryl group.
• The vitamin part of coenzyme A is pantothenic acid.
• The acetyl group of acetyl CoA is bound as a highenergy thioester.
O
CH3 -C-S-CoA
Acetyl coenzyme A
(An acyl CoA )
27-14
Coenzyme A
• Figure 27.7 The structure of coenzyme A.
27-15
Citric Acid Cycle
• Overview: the two-carbon acetyl group of acetyl CoA is
fed into the cycle and two CO2 are given off.
• There are four oxidation steps in the cycle.
Ace tyl-C oA
C oA
H + + N AD H
N AD +
C i tri c
aci d
cycl e
(8 ste ps)
C oA
FAD H2
N AD +
N AD H + H +
CO 2
N AD +
FAD
GTP
GDP
N AD H + H +
CO 2
27-16
Citric Acid Cycle
Step 1: The condensation of acetyl CoA with oxaloacetate:
• The high-energy thioester of acetyl CoA is hydrolyzed.
• This hydrolysis provides the energy to drive Step 1.
O
CH3 C-SCoA
Acetyl-CoA
+
O C-COO
CH2 -COO
Oxaloacetate
citrate
s yn th ase
CH2 -COO+ CoA-SH
HO C-COOCoenzyme A
CH2 -COOCitrate
• Citrate synthase, an allosteric enzyme, is inhibited by
NADH, ATP, and succinyl-CoA.
27-17
Citric Acid Cycle
Step 2: Dehydration and rehydration, catalyzed by
aconitase, gives isocitrate.
CH2 -COO CH2 -COO - H2 O
HO C-COO C-COO CH2 -COO
C i trate
-
CH- COO
-
Acon itate
H2 O
Acon itas e
CH2 -COO H C-COO HO CH- COO Isocitrate
• Citrate and aconitate are achiral; neither has a
stereocenter.
• Isocitrate is chiral; it has 2 stereocenters and 4
stereoisomers are possible.
• Only one of the 4 possible stereoisomers is formed in
the cycle.
27-18
Citric Acid Cycle
Step 3: Oxidation of isocitrate to oxalosuccinate followed
by decarboxylation gives a-ketoglutarate.
CH2 -COO - N AD +
H C-COO HO CH- COO
Isocitrate
-
N AD H + H+
i socitrate
de h ydroge n as e
CH2 -COO H C-COO O C-COO O xalos u cci n ate
CO 2
CH2 -COO H C-H
O C-COO a-Ketoglu tarate
• Isocitrate dehydrogenase is an allosteric enzyme; it is
inhibited by ATP and NADH, and activated by ADP and
NAD+.
27-19
Citric Acid Cycle
Step 4: Oxidative decarboxylation of a-ketoglutarate to
succinyl-CoA.
CoA -SH
CH 2 -COO CH 2
N AD +
N AD H
CH 2 -COO CH 2
-
O C-COO
a-Ketoglu tarate
a-ke togl u tarate
de h ydroge n as e O C SCoA
S u cci n yl -C oA
com ple x
+ CO 2
• The two carbons of the acetyl group of acetyl CoA are
still present in succinyl CoA.
• This multienzyme complex is inhibited by ATP, NADH,
and succinyl CoA. It is activated by ADP and NAD+.
27-20
Citric Acid Cycle
• Step 5: Formation of succinate.
CH2 -COOCH2
O C SCoA
succi nyl -Co A
CH
-COO
sy
nth
etase
2
+ GDP + Pi
+ GTP + CoA-SH
Su cci ny l-Co A
CH2 -COO-
Su cci nate
• The two CH2-COO- groups of succinate are now
equivalent.
• This is the first, and only, energy-yielding step of the
cycle. A molecule of GTP is produced.
27-21
Citric Acid Cycle
• Step 6: Oxidation of succinate to fumarate.
CH2 -COO -
FAD
CH2 -COO -
s uccinate
de hydroge nas e
Succi nate
H
FADH2
-
OOC
C
C
COOH
Fumarate
• Step 7: Hydration of fumarate to L-malate.
H
-
C
C
COO-
OOC
H
Fu marate
H 2 O HO CH- COO
CH 2 -COO fum aras e
L-Malate
• Malate is chiral and can exist as a pair of enantiomers;
It is produced in the cycle as a single stereoisomer.
27-22
Citric Acid Cycle
• Step 8: Oxidation of malate.
NAD + N ADH
HO CH- COO -
CH2 -COO L-Malate
mal ate
de h ydroge n as e
O C-COO
CH2 -COO O xaloacetate
• Oxaloacetate now can react with acetyl CoA to start
another round of the cycle by repeating Step 1.
• The overall reaction of the cycle is:
O
CH3 C-SCo A + GDP + Pi + 3 NAD + + FAD + 2 H2 O
2 CO2 + CoA + GT P + 3 NADH + FADH2 + 3 H+
27-23
Citric Acid Cycle
Control of the cycle:
• Controlled by three feedback mechanisms.
• Citrate synthase: inhibited by ATP, NADH, and succinyl
CoA; also product inhibition by citrate.
• Isocitrate dehydrogenase: activated by ADP and NAD+,
inhibited by ATP and NADH.
• a-Ketoglutarate dehydrogenase complex: inhibited by
ATP, NADH, and succinyl CoA; activated by ADP and
NAD+.
27-24
TCA Cycle in Catabolism
The catabolism of proteins, carbohydrates, and fatty acids
all feed into the citric acid cycle at one or more points:
Prote in s
C arboh ydrate s
Fatty Acids
Pyru vate
Ace tyl-C oA
O xal oace tate
a-Ketoglu tarate i nte rme di ate s
S u cci n yl-C oA of th e ci tric
Fu marate
aci d cycl e
Mal ate
27-25
Oxidative Phosphorylation
Carried out by four closely related multisubunit
membrane-bound complexes and two electron carriers,
coenzyme Q and cytochrome c.
• In a series of oxidation-reduction reactions, electrons
from FADH2 and NADH are transferred from one
complex to the next until they reach O2.
• O2 is reduced to H2O.
O2 + 4H+ + 4e-
2H2 O + energy
• As a result of electron transport, protons are pumped
across the inner membrane to the intermembrane
space.
27-26
Oxidative Phosphorylation
• Figure 27.10 Schematic diagram of the electron and H+
transport chain and subsequent phosphorylation.
27-27
Complex I
The sequence starts with Complex I.
• This large complex contains some 40 subunits, among
them are a flavoprotein, several iron-sulfur (FeS)
clusters, and coenzyme Q (CoQ, ubiquinone).
• Complex I oxidizes NADH to NAD+.
• The oxidizing agent is CoQ, which is reduced to CoQH2.
NADH + H+ + CoQ
NAD+ + CoQH2 + energy
• Some of the energy released in the oxidation of NAD+ is
used to move 2H+ from the matrix into the
intermembrane space.
27-28
Complex II
• Complex II oxidizes FADH2 to FAD.
• The oxidizing agent is CoQ, which is reduced to CoQH2.
FADH2 + CoQ
FAD + CoQH2 + energy
• The energy released in this reaction is not sufficient to
pump protons across the membrane.
27-29
Complex III
• Complex III delivers electrons from CoQH2 to
cytochrome c (Cyt c).
CoQH2 + 2Cyt c (reduced)
CoQ + 2H+ + 2Cyt c (oxidized)
• This integral membrane complex contains 11 subunits,
including cytochrome b, cytochrome c1, and FeS
clusters.
• Complex III has two channels through which the two H+
from each CoQH2 oxidized are pumped from the matrix
into the intermembrane space.
27-30
Complex IV
• Complex IV is also known as cytochrome oxidase.
• It contains 13 subunits, one of which is cytochrome a3
• Electrons flow from Cyt c (oxidized) in Complex III to
Cyt a3 in Complex IV.
• From Cyt a3 electrons are transferred to O2.
O2 + 4H+ + 4e-
2H2 O + energy
• During this redox reaction, H+ are pumped from the
matrix into the intermembrane space.
Summing the reactions of Complexes I - IV, six H+ are
pumped out per NADH and four H+ per FADH2.
27-31
Chemiosmotic Pump
To explain how electron and H+ transport produce the
chemical energy of ATP, Peter Mitchell proposed the
chemiosmotic theory that electron transport is
accompanied by an accumulation of protons in the
intermembrane space of the mitochondrion, which in turn
creates osmotic pressure; the protons driven back to the
mitochondrion under this pressure generate ATP.
• The energy-releasing oxidations give rise to proton
pumping and a pH gradient is created across the inner
mitochondrial membrane.
• There is a higher concentration of H+ in the
intermembrane space than inside the mitochondria.
• This proton gradient provides the driving force to
propel protons back into the mitochondrion through
the enzyme complex called proton translocating
27-32
ATPase.
Chemiosmotic Pump
• Protons flow back into the matrix through channels in
the F0 unit of ATP synthase.
• The flow of protons is accompanied by formation of
ATP in the F1 unit of ATP synthase.
ADP + Pi
ATP + H2O
The functions of oxygen are:
• To oxidize NADH to NAD+ and FADH2 to FAD so that
these molecules can return to participate in the citric
acid cycle.
• Provide energy for the conversion of ADP to ATP.
27-33
Chemiosmotic Pump
• The overall reactions of oxidative phosphorylation are:
NADH + 3ADP + 12 O2 + 3Pi + H+
FADH2 + 2ADP + 12 O2 + 2Pi
NAD+ + 3ATP + H2 O
FAD + 2ATP + H2 O
• Oxidation of each NADH gives 3ATP.
• Oxidation of each FADH2 gives 2 ATP.
27-34
Energy Yield
A portion of the energy released during electron transport
is now built into ATP.
• For each two-carbon acetyl unit entering the citric acid
cycle, we get three NADH and one FADH2.
• For each NADH oxidized to NAD+, we get three ATP.
• For each FADH2 oxidized to FAD, we get two ATP.
• Thus, the yield of ATP per two-carbon acetyl group
oxidized to CO2 is:
3 ATP
= 9 ATP
NADH
2 ATP
1 FADH2 x
= 2 ATP
FADH2
1 GTP
= 1 ATP
= 12 ATP
3 NADH x
27-35
Other Forms of Energy
The chemical energy of ATP is converted by the body to
several other forms of energy:
Electrical energy
• The body maintains a K+ concentration gradient across
cell membranes; higher inside and lower outside.
• It also maintains a Na+ concentration gradient across
cell membranes; lower inside, higher outside.
• This pumping requires energy, which is supplied by the
hydrolysis of ATP to ADP.
• Thus, the chemical energy of ATP is transformed into
electrical energy, which operates in neurotransmission.
27-36
Other Forms of Energy
Mechanical energy
• ATP drives the alternating association and dissociation
of actin and myosin and, consequently, the contraction
and relaxation of muscle tissue.
Heat energy
• Hydrolysis of ATP to ADP yields 7.3 kcal/mol.
• Some of this energy is released as heat to maintain
body temperature.
27-37
Chapter 27 Bioenergetics
Ace tyl-C oA
C oA
H + + N AD H
N AD +
C i tri c
aci d
cycl e
(8 ste ps)
C oA
FAD H2
N AD +
N AD H + H +
CO 2
N AD +
FAD
GTP
GDP
N AD H + H +
CO 2
End
Chapter 27
27-38