Download Cellular respiration

Metabolism
• Functions of food
• source of energy
• essential nutrients
• stored for future use
• Metabolism is all the chemical reactions of the
body
• some reactions produce the energy which is stored in ATP that other
reactions consume
• all molecules will eventually be broken down and recycled or excreted from
the body
26-1
Catabolism and Anabolism
• Catabolic reactions breakdown complex organic
compounds
• providing energy (exergonic)
• glycolysis, Krebs cycle and electron transport
• Anabolic reactions synthesize complex molecules from
small molecules
• requiring energy (endergonic)
• Exchange of energy requires use of ATP (adenosine
triphosphate) molecule.
26-2
ATP Molecule & Energy
• Each cell has about 1 billion ATP molecules that last for less than
one minute
• Over half of the energy released from ATP is converted to heat
26-3
Energy Transfer
• Energy is found in the bonds between atoms
• Oxidation is a decrease in the energy content of a molecule
• Reduction is the increase in the energy content of a
molecule
• Oxidation-reduction reactions are always coupled within
the body
• w
• Whenever a substance is oxidized, another is almost simultaneously
reduced
26-4
Oxidation and Reduction
 Biological oxidation involves the loss of electron and a
proton (hydrogen atom)
 D
 Dehydrogenation reactions require coenzymes to transfer
hydrogen atoms to another compound
 Common coenzymes of living cells that carry H+
 NAD (nicotinamide adenine dinucleotide )
 NADP (nicotinamide adenine dinucleotide phosphate )
 FAD (flavin adenine dinucleotide )
NAD+ + 2 H  NADH + H+
 Biological reduction is the addition of electron and a
proton (hydrogen atom) to a molecule
 Increase in potential energy of the molecule
26-5
Please note that due to differing
operating systems, some animations
will not appear until the presentation is
viewed in Presentation Mode (Slide
Show view). You may see blank slides
in the “Normal” or “Slide Sorter” views.
All animations will appear after viewing
in Presentation Mode and playing each
animation. Most animations will require
the latest version of the Flash Player,
which is available at
http://get.adobe.com/flashplayer.
Carbohydrate Metabolism
• Dietary carbohydrate burned as fuel within hours of absorption
• All oxidative carbohydrate consumption is essentially a matter of
glucose catabolism
C6H12O6 + 6O2  6CO2 + 6H2O+ energy
• Function of this reaction is to transfers energy from glucose to ATP
• Not to produce carbon dioxide and water
26-7
Glucose Catabolism
• Glucose catabolism – a series of small steps, each controlled by a
separate enzyme, in which energy is released in small
manageable amounts, and as much as possible, is transferred to
ATP and the rest is released as heat
• Three major pathways of glucose catabolism
• Glycolysis
• Glucose (6C) split into 2 Pyruvic acid molecules (3C)
• Anaerobic fermentation
• Occurs in the absence of oxygen
• Reduces pyruvic acid to lactic acid
• Aerobic respiration
• Occurs in the presence of oxygen
• Completely oxidizes pyruvic acid to CO2 and H2O
26-8
Mechanisms of ATP Generation
• Phosphorylation is bond attaching 3rd
phosphate group contains stored energy
• Mechanisms of phosphorylation
• Within animals
• Substrate-level phosphorylation - a highenergy from an intermediate in catabolism is
added to ADP.
• In cytosol
• Oxidative phosphorylation - energy is
released as electrons are passed to a series of
electron acceptors (an electron transport
chain) and finally to O2
• In mitochondria
• In chlorophyll-containing plants or bacteria
• Photophosphorylation
26-9
Overview of substrate level phosphorylation
ATP Production
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Key
Carbon atoms
Glucose
ATP
Phosphate
groups
1 Phosphorylation
ADP
Glucose 6-phosphate
Glycogen
Fat
Fructose 6-phosphate
ATP
2 Priming
ADP
Fructose 1,6-diphosphate
3 Cleavage
2 PGAL
2 Pi
2 NAD+
2 NADH + 2 H+
4 Oxidation
2
2 ADP
2 H2O
2 ATP
2
5 Dephosphorylation
2 ADP
2 ATP
2
2 pyruvic acid
2 NADH + 2 H+
2 NAD+
2
2 lactic acid
26-10
Anaerobic fermentation
Aerobic respiration
Steps of Glycolysis (1)
1. Phosphorylation
• glucose enters cell has phosphate
added - ATP used
• maintains favorable concentration
gradient, prevents glucose from
leaving cell
2. Priming
• isomerization occurs
• phosphorylation further activates
molecule - ATP used
3. Cleavage
• molecule split into 2 three-carbon
molecules (PGAL –
phosphoglyceraldehyde)
26-11
Steps of Glycolysis (2)
4. Oxidation
 Removes 2 H atoms
 NAD+ + 2H  NADH + H+
5. Dephosphorylation
 transfers phosphate groups to ADP to form
ATP
 4 ATPs produced (2 ATP used) for a net
gain of 2 ATP
 produces 2 pyruvic acid
26-12
Steps of Glycolysis
• 4 ATP are produced but 2 ATP were consumed to initiate
glycolysis, so net gain is 2 ATP per glucose molecule
• Some energy originally in the glucose is contained in the ATP,
some in the NADH, some is lost as heat, but most of the energy
remains in the pyruvic acid
• End-products of glycolysis are:
• 2 pyruvic acid + 2 NADH + 2 ATP
26-13
Anaerobic Fermentation
• Fate of pyruvic acid depends on oxygen availability
• In an exercising muscle, demand for ATP > oxygen
supply; ATP produced by glycolysis
• Glycolysis can not continue without supply of NAD+
• NADH reduces pyruvic acid to lactic acid, restoring NAD+
• Lactic acid travels to liver to be oxidized back to
pyruvic when O2 is available (oxygen debt)
• then stored as glycogen or released as glucose
• Fermentation is inefficient way to produce ATP
26-14
Anaerobic Fermentation
• Lactic acid is toxic - leaves the cells that generate it and enter the
bloodstream and transported to the liver
• When oxygen becomes available the liver oxidized it back to pyruvic
acid
• Liver can convert lactic acid back to G6P and can polymerize it to form glycogen
for storage
• Remove phosphate group and release free glucose into the blood
• Drawbacks of anaerobic fermentation
• Wasteful, because most of the energy of glucose is still in the lactic acid and
has contributed no useful work
• Lactic acid is toxic and contributes to muscle fatigue
• Skeletal muscle is relatively tolerant of anaerobic fermentation,
cardiac muscle less so
• the brain employs no anaerobic fermentation
26-15
Aerobic Respiration
• Most ATP generated in mitochondria, which requires oxygen as final
electron acceptor
• In the presence of oxygen, pyruvic acid enters the mitochondria
and is oxidized by aerobic respiration
• Occurs in two principal steps:
• Matrix reactions – their controlling enzymes are in the fluid of the
mitochondrial matrix
• Membrane reactions - whose controlling enzymes are bound to the
membranes of the mitochondrial cristae
26-16
Mitochondrial Matrix Reactions
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Pyruvic acid (C3)
6
CO2
Pyruvic acid oxidation
NAD+
7
NADH + H+
Acetyl group (C2)
8
Acetyl-Co A
Coenzyme A
H2O
9
Citric acid (C6)
Oxaloacetic acid (C4)
H2O
10
NADH + H+
NAD+
(C6)
Citric
acid
cycle
18
H2O
NAD+
11
Citric acid (Krebs) Cycle
NADH + H+
(C4)
12
CO2
17
(C5)
H2O
13
Occurs in
mitochondrial
matrix
(C4)
NADH + H+
14
16
FADH2
NAD+
(C4)
CO2
FAD
(C4)
Pi
15
GTP
GDP
26-17
ADP
ATP
Mitochondrial Matrix Reactions
 Three steps prepare pyruvic acid to enter citric
acid cycle
6. Decarboxylation so that a 3-carbon
compound becomes a 2-carbon compound
 CO2 removed from pyruvic acid
7. Convert that to an acetyl group (acetic
acid)
 NAD+ removes hydrogen atoms from the C2
compound
8. Acetyl group binds to coenzyme A
 results in acetyl-coenzyme A (acetyl-CoA)
26-18
Mitochondrial Matrix Reactions
9. Citric Acid (Krebs) Cycle
• acetyl-Co A (a C2 compound) combines with a
C4 to form a C6 compound (citric acid)-- start
of cycle
• hydrogen atoms are removed and accepted by
NAD+
• another CO2 is removed and the substrate
becomes a five-carbon chain
• previous step repeated removing another free
CO2 leaving a four-carbon chain
• ATP
• two hydrogen atoms are removed and accepted
by the coenzyme FAD
• two final hydrogen atoms are removed and
transferred to NAD+
• reaction generates oxaloacetic acid, which
starts the cycle again
26-19
Please note that due to differing
operating systems, some animations
will not appear until the presentation is
viewed in Presentation Mode (Slide
Show view). You may see blank slides
in the “Normal” or “Slide Sorter” views.
All animations will appear after viewing
in Presentation Mode and playing each
animation. Most animations will require
the latest version of the Flash Player,
which is available at
http://get.adobe.com/flashplayer.
Summary of Matrix Reactions
2 pyruvate + 6H2O  6CO2
2 ADP + 2 Pi  2 ATP
8 NAD+ + 8 H2  8 NADH + 8 H+
2 FAD + 2 H2  2 FADH2
• Carbon atoms of glucose have all been carried away as CO2 and
exhaled
• Energy lost as heat, stored in 2 ATP, 8 reduced NADH, 2 FADH2
molecules of the matrix reactions and 2 NADH from glycolysis
• Citric acid cycle is a source of substances for synthesis of fats and
nonessential amino acids
26-21
Membrane Reactions
 Membrane reactions have two purposes:
 to further oxidize NADH and FADH2 and
transfer their energy to ATP
 to regenerate NAD+ and FAD and make them
available again to earlier reaction steps
10. Mitochondrial electron-transport
chain – series of compounds (enzyme
complexes) that carry out this series of
membrane reactions
 most bound to the inner mitochondrial
membrane
 arranged in a precise order that enables each
one to receive a pair of electrons from the
member on the left side of it.
 pass electrons to member on the other side
26-22
Please note that due to differing
operating systems, some animations
will not appear until the presentation is
viewed in Presentation Mode (Slide
Show view). You may see blank slides
in the “Normal” or “Slide Sorter” views.
All animations will appear after viewing
in Presentation Mode and playing each
animation. Most animations will require
the latest version of the Flash Player,
which is available at
http://get.adobe.com/flashplayer.
Electron Transport Chain
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
50
NADH + H+
NAD+
FMN
Relative free energy (kcal/mole)
Fe-S
40
FADH2
Enzyme complex 1
FAD
CoQ
30
Figure 26.5
Cyt b
Fe-S
Cyt c1
20
Enzyme complex 2
Cyt c
Cu
10
Cyt a
Cyt a3
Enzyme complex 3
½ O2 + 2 H+
H2O
0
Reaction progress
26-24
Chemiosmotic Mechanism
• Electron transport chain energy fuels respiratory enzyme
complexes
• pump protons from matrix into space between inner and outer mitochondrial
membranes
• creates steep electrochemical gradient for H+ across inner mitochondrial
membrane
• Inner membrane is permeable to H+ at channel proteins called ATP
synthase
• Chemiosmotic mechanism - H+ current rushing back through these
ATP synthase channels drives ATP synthesis
26-25
Please note that due to differing
operating systems, some animations
will not appear until the presentation is
viewed in Presentation Mode (Slide
Show view). You may see blank slides
in the “Normal” or “Slide Sorter” views.
All animations will appear after viewing
in Presentation Mode and playing each
animation. Most animations will require
the latest version of the Flash Player,
which is available at
http://get.adobe.com/flashplayer.
Overview of ATP Production
• NADH releases an electron pair to electron transport system and
H+ to prime pumps
• enough energy to synthesize 2.5 ATP
• FADH2 releases its electron pairs further along electron-transport
system
• enough energy to synthesize 1.5 ATP
• Complete aerobic oxidation of glucose to CO2 and H2O produces
32 ATP
• efficiency rating of 40% - 60% is lost as heat
26-27
26-28
ATP Generated by Oxidation of Glucose
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Glucose
2 ATP
Glycolysis
(net)
2 NADH + 2 H+
Cytosol
2 pyruvate
Mitochondria
2 NADH + 2 H+
CO2
6 NADH + 6 H+
Citric acid
cycle
2 ATP
2 FADH2
Electron-transport
chain
O2
H2O
3 ATP
25
ATP
Total 32
ATP
26-29
Glycogen Metabolism
 ATP is quickly used after it is formed
 it is an energy transfer molecule, not an energy storage molecule
 converts the extra glucose to other compounds better suited for energy
storage (glycogen and fat)
 Glycogenesis - synthesis of glycogen
 stimulated by insulin
 chains glucose monomers together
 Glycogenolysis – hydrolysis of glycogen
 releases glucose between meals
 stimulated by glucagon and epinephrine
 only liver cells can release glucose back into blood
 Gluconeogenesis - synthesis of glucose from noncarbohydrates,
such as glycerol and amino acids
 occurs chiefly in the liver and later, kidneys if necessary
26-30
Glucose Storage and Use
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Blood
glucose
Extracellular
Intracellular
Glucose
6-phosphatase
(in liver, kidney,
and intestinal cells)
Hexokinase
(in all cells)
Glucose 6-phosphate
Glycogen
synthase
Key
Pi
Glucose
1-phosphate
Glycogenesis
Glycogenolysis
Glycogen
phosphorylase
Glycogen
Pi
Glycolysis
Figure 26.8
26-31
Lipids
• Triglycerides are stored in body’s adipocytes
• constant turnover of lipid molecules every 2 - 3 weeks
• released into blood, transported and either oxidized or redeposited in other fat
cells
• Lipolysis – breaking down fat for fuel
• begins with the hydrolysis of a triglyceride to glycerol and fatty acids
• stimulated by epinephrine, norepinephrine, glucocorticoids, thyroid hormone, and
growth hormone
• glycerol easily converted to PGAL and enters the pathway of glycolysis
• generates only half as much ATP as glucose
• beta oxidation in the mitochondrial matrix catabolizes the fatty acid
components
• removes two carbon atoms at a time which bonds to coenzyme A
• forms acetyl-CoA, the entry point for the citric acid cycle
• a fatty acid with 16 carbons can yield 129 molecules of ATP
• richer source of energy than the glucose molecule
• Lipogenesis - synthesis of fat from other types of molecules
• amino acids and sugars used to make fatty acids and glycerol
• PGAL can be converted to glycerol
26-32
Lipogenesis and Lipolysis Pathways
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Glucose
Glucose 6-phosphate
Stored
triglycerides
Glycerol
PGAL
Fatty acids
Glycerol
Beta oxidation
Pyruvic
acid
Fatty
acids
Acetyl groups
New
triglycerides
Acetyl-Co A
Ketone bodies
β-hydroxybutyric acid
Acetoacetic acid
Acetone
Citric
acid
cycle
Key
Lipogenesis
Lipolysis
26-33
Ketogenesis
• Fatty acids catabolized into acetyl groups (by beta-oxidation in
mitochondrial matrix) may:
• enter citric acid cycle as acetyl-CoA
• undergo ketogenesis
• metabolized by liver to produce ketone bodies
• acetoacetic acid
• -hydroxybutyric acid
• acetone
• rapid or incomplete oxidization of fats raises blood ketone levels
(ketosis) and may lead to a pH imbalance (ketoacidosis)
26-34
Proteins
• Amino acids in the pool can be converted to others
• Free amino acids also can be converted to glucose and fat or
directly used as fuel
• Conversions involve three processes:
• deamination – removal of an amino group (-NH2)
• amination – addition of -NH2
• transamination – transfer of -NH2 from one molecule to another
• As fuel - first must be deaminated (removal of -NH2)
• what remains is keto acid and may be converted to pyruvic acid, acetylCoA, or one of the acids of the citric acid cycle
• during shortage of amino acids, citric acid cycle intermediates can be
aminated and converted to amino acids
• in gluconeogenesis, keto acids are used to synthesis glucose
26-35
Learning objectives
• Carbohydrate metabolism
• Describe the principle reactants and poroducts of glucose oxidation
• Contrast thefunctions and products of anaerobic fermentation and aerobic
respiration
• Explain where and how cells produce ATP
• Describe the production, function and use of glycogen
26-36