Download METABOLISM CATABOLISM AND ANABOLISM ATP MOLECULE

METABOLISM


CATABOLISM AND ANABOLISM
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
Catabolic reactions breakdown complex organic
compounds
 providing energy (exergonic)
 glycolysis, Krebs cycle and electron transport
A b li reactions
Anabolic
ti
synthesize
th i complex
l
molecules from small molecules
 requiring energy (endergonic)
Exchange of energy requires use of ATP
(adenosine triphosphate) molecule.
26-2
ENERGY TRANSFER
ATP MOLECULE & ENERGY
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




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

whenever a substance is oxidized, another is
almost simultaneously reduced.
26-4
26-3
OXIDATION AND REDUCTION

Biological oxidation involves the loss of electron
and a proton (hydrogen atom)
 dehydrogenation reactions require coenzymes
to transfer hydrogen atoms to another
compound
li i cells
ll th
 common coenzymes off living
thatt carry H
H+





NAD (nicotinamide adenine dinucleotide )
NADP (nicotinamide adenine dinucleotide phosphate )
FAD (flavin adenine dinucleotide )
NAD+ + 2 H  NADH + H+
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Biological reduction is the addition of electron and
a proton (hydrogen atom) to a molecule
 increase in potential energy of the molecule
26-5
1
CARBOHYDRATE METABOLISM
GLUCOSE CATABOLISM
Dietary carbohydrate burned as fuel within
hours of absorption
 All oxidative carbohydrate consumption is
essentially a matter of 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

C6H12O6 + 6O2  6CO2 + 6H2O+ energy
glucose (6C) split into 2 pyruvic acid molecules (3C)
 anaerobic
fermentation
occurs in the absence of oxygen
 reduces pyruvic acid to lactic acid


Function of this reaction is to transfers energy
from glucose to ATP
 not
 aerobic
respiration
occurs in the presence of oxygen
 completely oxidizes pyruvic acid to CO2 and H2O

to produce carbon dioxide and water
26-7
26-8
OVERVIEW OF ATP PRODUCTION
MECHANISMS OF ATP GENERATION
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Key
Glucose
Carbon atoms
ATP
Phosphate
groups
1 Phosphorylation
ADP


Phosphorylation is
 bond attaching 3rd phosphate
group contains stored energy
Mechanisms of phosphorylation
 within animals


Glucose 6-phosphate
Glycogen
Fat
Fructose 6-phosphate
ATP
2 Priming
ADP
Fructose 1,6-diphosphate
3 Cleavage
2 PGAL
2 Pi
2 NAD+
substrate-level phosphorylation in cytosol
oxidative phosphorylation in mitochondria
2 NADH + 2 H+
4 Oxidation
2
2 ADP
2 H2O
 in
chlorophyll-containing plants
or bacteria

2 ATP
5 Dephosphorylation
2
2 ADP
2 ATP
2
2 pyruvic acid
photophosphorylation.
2 NADH + 2 H+
2 NAD+
2
2 lactic acid
26-9
Anaerobic fermentation
STEPS OF GLYCOLYSIS (1)






glucose enters cell has
phosphate added - ATP used
maintains favorable
concentration gradient,
prevents glucose from leaving
cell
Oxidation



isomerization occurs
phosphorylation further
activates molecule - ATP used

Cleavage

molecule split into 2 threecarbon molecules

26-11
removes H+
NAD+ + H  NADH
Dephosphorylation

Priming

26-10
STEPS OF GLYCOLYSIS (2)
Phosphorylation

Aerobic respiration
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
Animation
26-12
2
ANAEROBIC FERMENTATION
STEPS OF GLYCOLYSIS




4 ATP are produced but 2 ATP were consumed to
initiate glycolysis, so net gain is 2 ATP per glucose
molecule

Fate of pyruvic acid depends on oxygen
availability
In an exercising muscle, demand for ATP > oxygen
supply; ATP produced by glycolysis


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

Lactic acid travels to liver to be oxidized back to
pyruvic when O2 is available (oxygen debt)

Fermentation is inefficient, not favored by brain or
heart

End-products of glycolysis are:
 2 pyruvic acid + 2 NADH + 2 ATP
glycolysis can not continue without supply of NAD+
NADH reduces pyruvic acid to lactic acid
acid, restoring NAD+
then stored as glycogen or released as glucose
26-14
26-13
ANAEROBIC FERMENTATION







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
p y
polymerize
it to form gglycogen
y g for storage
g
remove phosphate group and release free glucose into the blood

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
Drawbacks of anaerobic fermentation



enter bloodstream and transported to the liver
when oxygen becomes available the liver oxidized it back to pyruvic
acid
oxygen is part of the oxygen debt created by exercising muscle
Liver can also convert lactic acid back to G6P and can:


AEROBIC RESPIRATION
Lactic acid leaves the cells that generate it
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
26-16
MITOCHONDRIAL MATRIX REACTIONS
MITOCHONDRIAL MATRIX REACTIONS
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Pyruvic acid (C3)
6
CO2

Pyruvic acid oxidation
NAD+
Three steps prepare pyruvic acid
to enter citric acid cycle
7
NADH + H+
Acetyl group (C2)

decarboxylation so that a 3-carbon
compound becomes a 2-carbon
compound

convert that to an acetyl group
(acetic acid)
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+
(C4)

CO2
FAD
(C4)
Pi
15
GTP
NAD+ removes hydrogen atoms from
the C2 compound
acetyl group binds to coenzyme A
14
16
FADH2
NAD+
CO2 removed from pyruvic acid
results in acetyl-coenzyme A (acetylCoA)
GDP
26-17
ADP
ATP
26-18
3
MITOCHONDRIAL MATRIX REACTIONS

Citric Acid 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
five-carbon
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
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26-19
SUMMARY OF MATRIX REACTIONS
MEMBRANE 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

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

Mi h d i l electron-transport
l
h i
Mitochondrial
chain
– series of compounds 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
26-21
26-22
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
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40
FADH2
Enzyme complex 1
FAD
CoQ
30
Figure 26
26.5
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
4
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 (ANIMATION)
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26-25
OVERVIEW OF ATP PRODUCTION

NADH releases an electron pair to electron
transport system and H+ to prime pumps
 enough

FADH2 releases its electron pairs further along
electron-transport system
 enough

energy to synthesize 3 ATP
energy to synthesize 2 ATP
Complete aerobic oxidation of glucose to CO2
and H2O produces 36-38 ATP
 efficiency
rating of 40% - 60% is lost as heat
26-28
26-27
ATP GENERATED BY OXIDATION OF GLUCOSE
GLYCOGEN METABOLISM
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Glucose
ATP is quickly used after it is formed


2 ATP
Glycolysis
(net)

2 NADH + 2 H+
2 pyruvate

Mitochondria


CO2
6 NADH + 6 H+


2 ATP

2 FADH2
O2
H2 O
4 ATP
28–30
ATP
Total 36–38
ATP
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

26-29
stimulated by insulin
chains glucose monomers together
Glycogenolysis – hydrolysis of glycogen

Citric acid
cycle
Electron-transport
chain
Glycogenesis - synthesis of glycogen
Cytosol
2 NADH + 2 H+
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)
occurs chiefly in the liver and later, kidneys if necessary
26-30
5
LIPIDS
GLUCOSE STORAGE AND USE
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood
glucose
Triglycerides are stored in body’s adipocytes
 constant
Extracellular
Intracellular
Glucose
6-phosphatase
(in liver, kidney,
and intestinal cells)
 released
into blood, transported and either oxidized or
redeposited in other fat cells
Hexokinase
(in all cells)

Glucose 6-phosphate
Glycogen
synthase
Key
Pi
Glycogen
phosphorylase
Lipogenesis - synthesis of fat from other types
of molecules
 amino
Glucose
1-phosphate
Glycogenesis
Glycogenolysis
turnover of lipid molecules every 2 - 3
weeks
acids and sugars used to make fatty acids
and glycerol
 PGAL can be converted to glycerol
Glycogen
Pi
Glycolysis
Figure 26.8
LIPIDS

LIPOGENESIS AND LIPOLYSIS PATHWAYS
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




Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Glucose
Glucose 6-phosphate
Stored
triglycerides
Glycerol
generates only half as much ATP as glucose
Citric
acid
cycle
Lipogenesis
Lipolysis
26-33
26-34
PROTEINS
citric acid cycle as acetyl-CoA
ketogenesis
g

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:
 undergo
g
 metabolized
New
triglycerides
Key
Fatty acids catabolized into acetyl groups (by
beta-oxidation in mitochondrial matrix) may:
 enter
Fatty
acids
Acetyl-Co A
Ketone bodies
β-hydroxybutyric acid
Acetoacetic acid
Acetone
KETOGENESIS

Pyruvic
acid
Acetyl groups
removes two carbon atoms at a time which bonds to coenzyme A
forms acetyl-CoA, the entry point for the citric acid cycle
richer source of energy than the glucose molecule
PGAL
Fatty acids
a fatty acid with 16 carbons can yield 129 molecules
of ATP

Glycerol
Beta oxidation
beta oxidation in the mitochondrial matrix catabolizes
the fatty acid components

26-32
26-31


by liver to produce ketone bodies

acetoacetic acid
 -hydroxybutyric acid
 acetone


As fuel - first must be deaminated (removal of -NH2)

 rapid
or incomplete oxidization of fats raises blood
ketone levels (ketosis) and may lead to a pH imbalance
(ketoacidosis)
26-35
deamination – removal of an amino group (-NH2)
amination – addition of -NH2
transamination – transfer of -NH2 from one molecule to another


what remains is keto acid and may be converted to pyruvic acid,
acetyl-CoA, 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
26-36
6