Transcript Chapter 19

Chapter 19
Bioenergetics; How the Body
Converts Food to Energy
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.
Metabolism
Metabolism is the sum of catabolism and anabolism.
Metabolism
Figure 19 .1
Simplified schematic
diagram of the
common metabolic
pathway, an
imaginary funnel
representing what
happens in the cell.
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.
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.
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.
Adenosine Triphosphate (ATP)
• Hydrolysis of the terminal phosphate (anhydride) of ATP
gives ADP, dihydrogen phosphate ion, and energy.
• Hydrolysis of a phosphoric anhydride liberates more
energy than the 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.
NAD+/NADH
•
Nicotinamide adenine dinucleotide (NAD+) is a biological
oxidizing agent.
+
The plus sign on NAD
represents the positive
charge on this nitrogen
O
CNH2
O
-
O-P-O-CH2
O
AMP H
N+
O
H
H
H
HO
Nicotinamide;
derived
from niacin
OH
a b-N-glycosidic
bond
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.
NAD+
NADH
• NADH is an electron and hydrogen ion transporting
molecule.
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
H C OH
CH2
O
O=P-O-AMP
O-
Ribitol
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.
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 high-energy
thioester.
Acetyl Coenzyme A
Coenzyme A
•
Figure 19.7 The structure of coenzyme A The business end
is the -SH (sulfhydryl) group at the left end.
Mercaptoethylamine
Pantothenic acid
Phosphorylated ADP
Citric Acid Cycle
Krebs Cycle
Citric Acid Cycle
• Figure 19.9 A simplified view of the citric acid cycle
showing only the carbon balance. The fuel is the twocarbon acetyl group of acetyl CoA. With each turn of the
cycle two carbons are released as CO2.
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.
Oxaloacetate
Acetyl CoA
• Citrate synthase, an allosteric enzyme, is inhibited by
NADH, ATP, and succinyl-CoA.
Citric Acid Cycle
Step 2: Dehydration and rehydration, catalyzed by
aconitase, gives isocitrate.
CH2 -COOHO C-COO
-
CH2 -COO
-H2 O
CH2 -COO-
C-COO
-
CH-COO
H2 O
Aconitase
CH2 -COOH C-COO HO CH-COO -
Citrate
Aconitate
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.
Citric Acid Cycle
Step 3: Oxidation of isocitrate to oxalosuccinate followed
by decarboxylation gives a-ketoglutarate.
CH2 -COOH C-COO HO CH-COO Isocitrate
NAD+
NADH + H+
isocitrate
dehydrogenase
CH2 -COOH C-COOO C-COOOxalosuccinate
CO2
CH2-COO H C-H
O C-COOa-Ketoglutarate
• Isocitrate dehydrogenase is an allosteric enzyme; it is
inhibited by ATP and NADH, and activated by ADP and
NAD+.
Citric Acid Cycle
Step 4: Oxidative decarboxylation of a-ketoglutarate to
succinyl-CoA.
CoA-SH
-
CH2 -COO
CH2
O C-COO-
a-Ketoglutarate
NAD
+
NADH
a-ketoglutarate
dehydrogenase
complex
-
CH2 -COO
CH2
+ CO 2
O C SCoA
Succinyl-CoA
• 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+.
Citric Acid Cycle
•
Step 5: Formation of succinate.
-
CH2 -COO
CH2
succinyl-CoA
CH
-COO
synthetase
2
+ GDP + Pi
+ GTP + CoA-SH
-
O C SCoA
CH2 -COO
Succinyl-CoA
Succinate
• 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.
Citric Acid Cycle
•
Step 6: Oxidation of succinate to fumarate.
•
Step 7: Hydration of fumarate to L-malate.
Malate is chiral and can exist as a pair of enantiomers; It
is produced in the cycle as a single stereoisomer.
Citric Acid Cycle
•
Step 8: Oxidation of malate.
•
• 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:
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+.
TCA Cycle in Catabolism
The catabolism of proteins, carbohydrates, and fatty acids
all feed into the citric acid cycle at one or more points:
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.
• As a result of electron transport, protons are pumped
across the inner membrane to the intermembrane
space.
Oxidative Phosphorylation
•
Figure 19.10 Schematic diagram of the electron and
H+ transport chain and subsequent phosphorylation.
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.
• Some of the energy released in the oxidation of NAD+ is
used to move 2H+ from the matrix into the
intermembrane space.
Complex II
• Complex II oxidizes FADH2 to FAD.
• The oxidizing agent is CoQ, which is reduced to CoQH2.
• The energy released in this reaction is not sufficient to
pump protons across the membrane.
Complex III
• Complex III delivers electrons from CoQH2 to cytochrome
c (Cyt c).
• 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.
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.
• 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.
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 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.
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.
Chemiosmotic Pump
•
The overall reactions of oxidative phosphorylation are:
•
Oxidation of each NADH gives 3ATP.
Oxidation of each FADH2 gives 2 ATP.
•
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:
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.
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.
Example

How many ATP molecules are generated for each H+
translocated through the ATPase complex?