Transcript Biosc_48_Chapter_5_lecture

Chapter 05
Cell Respiration
and Metabolism
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Introduction

Metabolism
a. All of the reactions in the body that require
energy transfer. Can be divided into:
1) Anabolism: requires the input of energy to
synthesize large molecules
2) Catabolism: releases energy by breaking
bonds between large molecules to form
smaller molecules
Catabolism Drives Anabolism



The catabolic reactions that break down glucose,
fatty acids, and amino acids serve as energy
sources for the anabolism of ATP.
Involves many oxidation-reduction reactions.
Complete catabolism of glucose requires oxygen
as the final electron acceptor.
1) Called aerobic cellular respiration.
2) Breaking down glucose requires many
enzymatically catalyzed steps, the first of
which are anaerobic.
I.
Glycolysis and the Lactic Acid
Pathway
Aerobic respiration of glucose

Occurs in three steps:
1) Glycolysis – occurs in the cytoplasm;
anaerobic
2) Citric acid (Krebs) cycle – occurs in the
matrix of the mitochondria; aerobic
3) Electron transport – occurs on cristae of
mitochondria inner membrane; aerobic
C6H12O6 + O2  6 CO2 + 6 H2O + ATP
Overview of Energy Metabolism
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Glycogen
in liver
Glucose
from digestive tract
Glucose
from liver
Capillary
Glucose
in blood plasma
Interstitial fluid
Plasma membrane
Glucose
in cell cytoplasm
Glycolysis
Pyruvic acid
Anaerobic
Cytoplasm
Lactic
acid
Metabolism
in skeletal muscle
into mitochondrion
Citric acid
cycle
Electron
transport
Aerobic
CO2 + H2O
Respiration
Mitochondrion
Glycolysis
1. First step in catabolism of glucose
2. Occurs in the cytoplasm of the cell
3. Glucose phosphorylated twice (using 2 ATP) and
converted into fructose 1,6-biphosphate
4. F 1,6-biP is split into two 3-Phosphoglyceraldehyde (3carbon molecule)
5. Each 3-carbon molecule proceed through similar
reactions
 3-P glyceraldehyde is phosphorylated to become
1,3-biphosphoglyceric acid.
 Two H+ is used to reduce NAD  NADH
Glycolysis
6. A phosphate is released from 1,3-BiP glyceric acid to
form 3-Phosphoglyceric acid
 Pi + ADP  ATP
7. 3-P glyceric acid isomerizes to 2-Phosphoglyceric acid
8. 2-P glyceric acid becomes Phosphoenolpyruvic acid
9. A phosphate is released from phosphoenolpyruvic acid
to form Pyruvic acid
 Pi + ADP  ATP
Glycolysis Pathway
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Glucose (C6H12O6)
ATP
1
ADP
Glucose 6-phosphate
2
Fructose 6-phosphate
ATP
3
ADP
Fructose 1,6-biphosphate
4
3–Phosphoglyceraldehyde
Dihydroxyacetone
phosphate
3–Phosphoglyceraldehyde
Pi
Pi
NADH
5
NADH
2H
5
2H
NAD
NAD
1,3–Biphosphoglyceric acid
ATP
1,3–Biphosphoglyceric acid
ATP
6
ADP
6
ADP
3–Phosphoglyceric acid
3–Phosphoglyceric acid
7
2–Phosphoglyceric acid
7
2–Phosphoglyceric acid
8
Phosphoenolpyruvic acid
ATP
8
Phosphoenolpyruvic acid
ATP
9
ADP
9
ADP
Pyruvic acid (C3H4O3)
Pyruvic acid (C3H4O3)
*Net Yield in Glycolysis

One Glucose (6-carbon molecule)    two
Pyruvic acid (3-carbon molecule)
C6H12O6  2 molecules C3H4O3 + 4H+

4 hydrogen ions used to reduce 2 molecules of
NAD.
2NAD + 4H+  2NADH + 2H+
*Net Energy Gain in Glycolysis



Glycolysis is exergonic, so some energy is
produced and used to drive the reaction
ADP + Pi  ATP
4 ATPs are generated.
Glucose requires activation at the beginning
from 2 ATP molecules.


Phosphorylation of glucose prevents it from
diffusing back through the plasma membrane
Net gain in glycolysis = 2 ATP
Use and Expenditure of Energy in Glycolysis
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1
ATP
ADP
ATP
2 NADH
ADP
2 NAD
Free energy
Glucose
2
2 ATP
2 ADP + 2 Pi
3
2 ATP
2 ADP + 2 Pi
Pyruvic acid
*Reactants and Products of Glycolysis
Glucose + 2 NAD + 2 ADP + 2 Pi 
2 Pyruvic acid + 2 NADH + 2 ATP
Lactic Acid Pathway

When there is no oxygen to complete the
breakdown of glucose, NADH has to give its
electrons to pyruvic acid. This results in the
reformation of NAD and the conversion of
pyruvic acid to lactic acid.
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NADH + H+
H
H
O
C
C
N AD
O
C
H
OH
H
Pyruvic acid
LDH
H
OH
C
C
O
C
OH
H
H
Lactic acid
Lactic Acid Pathway


Also called anaerobic metabolism or lactic
acid fermentation (Similar to how yeast
ferments glucose into alcohol)
Still yields a net gain of 2 ATP
a. Muscle cells can survive for awhile without
oxygen by using lactic acid fermentation.
b. RBCs can only use lactic acid fermentation
because they lack mitochondria.
II.
Aerobic Respiration
Introduction
1. Equation: C6H12O6 + O2  6 CO2 + 6 H2O
2. Similar to combustion except energy is released
in small, enzymatically controlled steps, not in
large amounts of heat
3. Begins with glycolysis, which produces:
a. 2 molecules pyruvic acid, 2 NADH, and 2 ATP
b. The pyruvic acid will be used in a metabolic pathway
called the citric acid cycle, and the NADH will be
oxidized to make ATP.
The Fate of Pyruvic Acid
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H
H
NAD
H
C
H
C
O
H
+
S
H
CoA
C
HO
NADH + H+
C
H
C
O
S
CoA
O
Pyruvic acid
Coenzyme A
Acetyl coenzyme A
+ CO2
The fate of pyruvic acid



Pyruvic acid leaves the cytoplasm and enters the
interior matrix of the mitochondria.
Carbon dioxide is removed to form acetic acid.
Acetic acid is combined with coenzyme A to form
acetyl CoA.
2 Pyruvic acid + Coenzyme A 
2 Acetyl CoA + 2 NADH + 2 CO2
Citric Acid Cycle
 Also called the citric acid cycle or the TCA
(tricarboxylic acid) cycle
 Acetyl CoA combines with oxaloacetic acid to
form citric acid.
 Citric acid starts the citric acid cycle.
 It is a cycle because citric acid moves
through a series of reactions to produce
oxaloacetic acid again.
Simplified Diagram of the Citric Acid Cycle
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Glycolysis
C3
Pyruvic acid
CYTOPLASM
NAD
CO2
Mitochondrial matrix
CoA
NADH + H+
C2 Acetyl CoA
Oxaloacetic acid C
4
CO2
Citric acid
cycle
α-Ketoglutaric acid
C5
CO2
C6
Citric acid
3 NADH + H+
1 FADH2
1 ATP
Important Events in the Citric Acid Cycle
 One guanosine triphosphate (GTP) is
produced, which donates a phosphate group
to ADP to form ATP.
 Three molecules NAD are reduced to NADH.
 One molecule FAD is reduced to FADH2.
 These events occur for each acetic acid, so it
happens twice for each glucose molecule.
The Complete Citric Acid Cycle
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H
H
O
C
C
COOH
HS – CoA
S
CoA
+ H2 O
H
COOH
Acetyl CoA (C2)
H
C
O
C
H
H2 O
H
C
H
HO
C
COOH
H
C
H
1
H2 O
COOH
2
H
COOH
Citric acid (C6)
COOH
C
H
C
COOH
C
H
COOH
Oxaloacetic acid (C4)
H2 O
COOH
3
cis-Aconitic acid (C6)
8
COOH
NADH
H
C
OH
H
C
H
H
C
H
H
C
COOH
H
C OH
+ H+
COOH
2H
Isocitric acid (C6)
NAD
COOH
NADH
+ H+
4
2H
Malic acid (C4)
NAD
7
H2 O
H
COOH
C
C
HOOC
FADH2
H
2H
Fumaric acid (C4)
CO2
FAD
6
ATP
COOH
H
C
H
H
C
H
COOH
ADP
NADH
GDP
NAD
COOH
C
H
C
H
C
O
+ H+
2H
GTP
H
CO2
H
COOH
α-Ketoglutaric acid (C5)
Succinic acid (C4)
5
H2 O
Products of the Citric Acid Cycle
For each Acetyl CoA:
 3 NADH, 1 FADH2,1 ATP, 2 CO2
 Since there are 2 Acetyl CoA that contribute
to the citric acid cycle...
Net yield
6 NADH, 2 FADH2, 2 ATP, 4 CO2
Electron Transport & Oxidative Phosphorylation

On the inner membrane (cristae) of the
mitochondria are molecules that serve as
electron transporters.
a. Include FMN, coenzyme Q, and several
cytochromes
b. These accept electrons from NADH and
FADH2. The hydrogens are not transported
with the electrons.
c. Oxidized FAD and NAD are reused.
Electron Transport Chain
a. Electron transport molecules pass the electrons
down a chain, with each being reduced and then
oxidized.
b. This is an exergonic reaction, and the
c. Energy produced is used to combine an ADP to
a phosphate ion to make ATP.
 An oxygen molecule is the last electron
acceptor in the chain  this process is called
oxidative phosphorylation.
d. Process is not 100%; difference is released as
heat
Electron Transport Chain
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NADH
FMN
NAD
FMNH2
2 H+
Electron energy
FADH2
FAD
2 e–
Oxidized
Fe2+
CoQ
Cytochrome b
Reduced
Fe3+
2 e–
Fe2+
Cytochrome
c1 and c
Cytochrome a
Fe3+
Fe2+
Fe3+
2 e–
Fe2+
H2O
Cytochrome a3
Fe3+
2 e–
2
H+
1
+ – O2
2
Coupling of electron transport to ATP
production

Chemiosmotic Theory
a. Electron transport fuels proton pumps, which pump
H+ from the mitochondrial matrix to the space
between the inner and outer membranes.
b. This sets up a huge concentration gradient of H+
between the membranes.
c. H+ can only move through the inner membrane
through structures called respiratory assemblies
d. Movement of H+ across the membrane provides
energy to the enzyme ATP synthase, which converts
ADP to ATP.
Oxidative Phosphorylation
Figure 5.9 The steps of oxidative phosphorylation
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Outer mitochondrial
membrane
Inner mitochondrial
membrane
2
H+
Intermembrane
space
Third
pump
Second
pump
H+
H+
1
2 H+
ATP
synthase
H2O
First pump
4H+
e–
1
4 H+
3
2 H + 1 /2 O2
ADP
+
Pi
H+
ATP
NAD+
Matrix
NADH
The Function of Oxygen





Act as final electron acceptor.
O2 oxididizes cytochrome a3, the last molecule in
the electron transport chain, by taking away its
electrons and forming water
Without a final acceptor, the whole process
would come to a halt.
The citric acid cycle and electron transport
require oxygen to continue.
Water is formed in the following reaction:
O2 + 4 e- + 4 H+  2 H2O
ATP Balance Sheet
1. Direct (substrate-level) phosphorylation in
glycolysis and the citric acid cycle yields 4 ATP.
2. Oxidative phosphorylation in electron transport
yields varying amounts of ATP, depending on
the cell and conditions.
a. Theoretically, each NADH yields 3 ATP and each
FADH2 yields 2 ATP.
b. In actuality, each NADH yields 2.5 ATP and
each FADH2 yields 1.5 ATP
 This difference accounts for energy needed
to move ATP out of the mitochondria
ATP yield
a. From glycolysis  2 NADH (which may be
converted to 2 FADH2 when inside mitochondria)
b. From pyruvic acid  2 NADH
c. From citric acid cycle  6 NADH and 2 FADH2
If NADH remains NADH:
If NADH becomes FADH2:
G: 2 NADH x 2.5 = 5 ATP
P: 2 NADH x 2.5 = 5 ATP
C: 6 NADH x 2.5 = 15 ATP
C: 2 FADH2 x 1.5 = 3 ATP
G: 2 ATP
C: 2 ATP
G: 2 FADH2 x 1.5 = 3 ATP
P: 2 NADH x 2.5 = 5 ATP
C: 6 NADH x 2.5 = 15 ATP
C: 2 FADH2 x 1.5 = 3 ATP
G: 2 ATP
C: 2 ATP
Total = 32 ATP
Total = 30 ATP
Detailed Accounting
III. Interconversion of Glucose, Lactic
Acid, and Glycogen
Glycogenesis and Glycogenolysis

Glycogenesis
a. Cells can’t store much glucose because it will pull
water into the cell via osmosis.
b. Glucose is stored as a larger molecule called
glycogen in the liver, skeletal muscles, and
cardiac muscles.
c. Glycogen is formed from glucose via
glycogenesis.
1) Glucose is phosphorylated, then isomerized to
Glucose 1-phosphate
2) Glycogen synthase removes the phosphate and
joins glucose together
Glycogenesis and Glycogenolysis

Glycogenolysis
a. The process of removing glucose molecules
from glycogen to be used by the body.

Glycogen phosphorylase adds Pi group to
glucose to form glucose 1-phosphate
b. G1P is isomerized into Glucose 6-phosphate
c. G6P can now enter glycolysis
d. In the liver, glucose 6-phosphatase can
remove phosphate from G6P to yield
Glucose, which is now free to enter the
circulation.
Glycogenesis and Glycogenolysis
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GLYCOGEN
Pi
Pi
1
2
Glucose 1-phosphate
Pi
Glucose
(blood)
ADP
ATP
Glucose 6-phosphate
Liver
only
Many
tissues
Fructose 6-phosphate
GLYCOLYSIS
Glucose
(blood)
The Cori Cycle
1. During exercise, skeletal muscles rapidly utilize
glucose and produce a high amount of lactic
acid.
2. Some lactic acid is converted to CO2 and H2O
3. Excess lactic acid is carried in the blood to the
liver.
4. Within the liver, the enzyme lactic acid
dehydrogenase converts lactic acid to pyruvic
acid and NADH.
The Cori Cycle
5. Pyruvic acid is then converted to glucose 6phosphate.
a. This can be used to make glycogen or
glucose
b. Pyruvic acid  Glucose = gluconeogenesis
(making “new” glucose from noncarbohydrate
molecules)
c. Glucose is carried in the blood to the muscle
cells, which completes the Cori Cycle.
The Cori Cycle
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Skeletal muscles
Liver
Glycogen
Glycogen
Exercise
1
Rest
9
Blood
Glucose 6-phosphate
Glucose 6-phosphate
Glucose
8
7
6
2
Pyruvic acid
Pyruvic acid
5
3
Lactic acid
Blood
4
Lactic acid
Common Metabolic Process Terms
IV. Metabolism of Lipids and Proteins
Introduction


Lipids and proteins can also be used for energy
via the same pathways used for the metabolism
of pyruvic acid.
When more food energy is taken into the body
than is needed to meet energy demands, we
can’t store ATP for later. Instead, glucose is
converted into glycogen and fat, and ATP
production is inhibited
Conversion of glucose into glycogen and fat
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Glycogen
Glucose 1-phosphate
Glucose
Glucose 6-phosphate
Fructose 6-phosphate
Fructose 1,6-biphosphate
Glycerol
Fat
3-Phosphoglyceraldehyde
Pyruvic acid
Fatty acids
Acetyl CoA
C6
C4
Oxaloacetic acid Citric acid
Citric acid
cycle
C5
-Ketoglutaric acid
Lipid Metabolism

As ATP levels rise after an energy-rich meal,
production of ATP is inhibited:
a. Glucose doesn’t complete glycolysis to form
pyruvic acid, and the acetyl CoA already
formed is joined together to produce a variety
of lipids, including cholesterol, ketone bodies,
and fatty acids.
b. Fatty acids combine with glycerol to form
triglycerides in the adipose tissue and liver =
lipogenesis.
Acetyl CoA  Lipids
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Bile acids
Steroids
Cholesterol
Ketone bodies
Acetyl CoA
Citric acid
(Krebs cycle)
Fatty acids
Triacylglycerol
(triglyceride)
Phospholipids
CO2
White Adipose Tissue (White Fat)
a. Fat stored in adipose tissue as triglycerides
b. Great way to store energy: 1 gram fat = 9 kcal
energy.
1) In a nonobese 155-pound man, 80-85% of his stored
energy is in fat. (140,000 calories)
c. Lipolysis: breaking triglycerides down into fatty
acids and glycerol using the enzyme lipase.
1) Fatty acids can then enter the blood as blood-borne
energy carriers and be used for energy elsewhere.
2) Glycerol is taken up by the liver and converted to
glucose through gluconeogenesis
β-oxidation of Fat
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Fatty acid
β

H
H
C
C
H
H
O
C
OH
CoA
1
ATP
AMP + PPi
Fatty acid
H
H
O
C
C
C
H
H
CoA
FAD
2
FADH2
H
H
O
C
C
C
Fatty acid
1.5 ATP
CoA
H
H2O
3
CoA
HO
H
O
C
C
C
H
H
Fatty acid
Fatty acid now
two carbons shorter
CoA
NAD
4
NADH
O
H
O
C
C
C
Fatty acid
5
2.5 ATP
+ H+
CoA
Acetyl CoA
Citric
acid
cycle
10 ATP
Fatty Acids as an Energy Source

β-oxidation: Enzymes remove acetic acid
molecules from fatty acids to form acetyl CoA.
a) For every 2 carbons from the fatty acid chain 
1 Acetyl CoA, 1 NADH, 1 FADH2 is formed.
b) Each acetyl CoA that enters the Citric acid cycle
will yield 10 ATP
A 16-carbon fatty acid:
8 Acetyl CoA = 80 ATP
7 NADH x 2.5 = 17.5 ATP
7 FADH2 x 1.5 = 10.5 ATP
Total = 108 ATP
Brown Adipose Tissue (Brown Fat)
a. Stored in different cells
b. Involved in thermogenesis (heat production),
especially in newborns
c. Adults also have some brown fat that contributes
to calories and heat production
d. Sympathetic release of norepinephrine causes
brown fat to form an uncoupling protein called
UCPI; H+ leaks out of inner mitochondrial
membrane, less ATP is formed, which leads to
use of fatty acids for more heat generation
Ketone Bodies






When the rate of lipolysis exceeds the rate of fatty
acid utilization (as in dieting, starvation, or
diabetes), the concentration of fatty acids in the
blood increases.
Liver cells convert the fatty acids into acetyl CoA
Two acetyl CoA combine to form acetoacetic acid
and β-hydroxybutyric acid
Along with acetone these form ketone bodies.
These are water-soluble molecules that circulate in
the blood.
Build-up in the blood can cause ketosis
Amino Acid Metabolism
1. Proteins provide nitrogen for the body
2. Amino acids from dietary proteins are needed to
replace proteins in the body.
3. If more amino acids are consumed than are
needed, the excess amino acids can be used for
energy or converted into carbohydrates or fat.
4. Our bodies can make 12 of the 20 amino acids
from other molecules. Eight of them (9 in
children) must come from the diet and are called
essential amino acids.
Essential Amino Acids
Transamination
a. A reaction which transfer the amine group (NH2)
from one AA to form another AA
b. Pyruvic acid and several citric acid cycle
intermediates (called keto acids) can be
converted to amino acids by adding an amine
group.
1) Requires vitamin B6 as a coenzyme
2) Each transamination requires a specific
enzyme
Transamination
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OH
O
HO
C
O
O
OH
C
O
OH
C
C
H
H
N
C
H
C
O
+
H
H
C
H
H
C
H
C
H
C
H
C
HO
+
H
C
H
H
C
H
C
H
H
C
H
C
HO
O
C
O
Glutamic acid
OH
N
H
O
C
HO
O
AST
HO
α-Ketoglutaric acid
Oxaloacetic acid
O
OH
C
O
O
O
OH
C
Aspartic acid
O
OH
C
C
H
H
N
C
H
H
C
O
C
H
+
H
C
H
H
C
H
H
H
ALT
C
O
H
C
H
H
C
H
C
HO
Glutamic acid
+
N
C
H
H
C
H
H
H
C
HO
O
Pyruvic acid
O
-Ketoglutaric acid
Alanine
Oxidative Deamination


If there are more amino acids than needed, the
amine group from glutamic acid can be stripped and
excreted as urea in the urine.
Oxidative deamination sometimes forms pyruvic
acid or another citric acid cycle intermediates.


These can be used to make energy or converted to
glucose or fat.
The formation of glucose from amino acids is called
gluconeogenesis and occurs in the Cori cycle.
Oxidative Deamination
(x2)
+
H2O
Amino Acids as Energy
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Alanine, cysteine,
glycine, serine,
threonine, tryptophan
NH3
Pyruvic acid
Urea
Leucine,
tryptophan,
isoleucine
NH3
Acetyl CoA
Urea
Asparagine,
aspartate
Arginine, glutamate,
glutamine, histidine,
proline
Citric acid
Urea
NH3
Oxaloacetic acid
–Ketoglutaric acid
NH3
Citric acid cycle
Phenylalanine,
tyrosine
Urea
NH3
Isoleucine,
methionine,
valine
Fumaric acid
Succinic acid
NH3
Urea
Urea
Uses of different energy sources
 Glucose and ketone bodies come from the
liver
 Fatty acids come from adipose tissue
 Lactic acid and amino acids come from
muscle
Different Energy Sources
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Glycogen
Glucose
Phosphoglyceraldehyde
Glycerol
Triacylglycerol
(triglyceride)
Lactic acid
Pyruvic acid
Acetyl CoA
Fatty acids
Amino acids
Protein
Urea
Ketone
bodies
C4
Citric
acid
cycle
C5
C6
Relative importance of different energy
sources to different organs