GLYCEROL METABOLISM
FATTY ACID METABOLISM
INTERRELATIONSHIP OF CARBOHYDRATE
AND LIPID METABOLISM
KETOSIS, ACIDOSIS, AND
DEHYDRATION
JANELLA MARIE R. ESPINO
BSED 4-R
 Is a highly coordinated cellular activity in which
many multienzyme systems (metabolic pathways)
cooperate to
(1) obtain chemical energy by capturing solar
energy or degrading energy-rich nutrients from the
environment;
METABOLISM
(2) convert nutrient molecules into the cell’s own
characteristic molecules, including precursors of
macromolecules;
(3) polymerize monomeric precursors into
macromolecules: proteins, nucleic acids, and
polysaccharides; and
(4) synthesize and degrade biomolecules required
for specialized cellular functions, such as membrane
lipids, intracellular messengers, and pigments.
 Metabolism, the sum of all the
METABOLISM
chemical transformations taking
place in a cell or organism, occurs
through a series of enzymecatalyzed reactions that constitute
metabolic pathways.
 Precursor for synthesis of
triacylglycerols and of phospholipids
in the liver and adipose tissue.
 When the body uses stored fat as a
GLYCEROL
METABOLISM
source of energy, glycerol and fatty
acids are released into the
bloodstream.
 In some organisms, the glycerol
component can enter glycolysis
pathway directly and thus provide
energy for cellular metabolism.
 The glycerol hydrolyzed from fats
GLYCEROL
METABOLISM
or complex lipids can also be a rich
energy source. The first step in
glycerol utilization is an activation
step.
 The body uses one ATP molecule
to form glycerol 1-phosphate,
which is the same as glycerol 3phosphate:
FATTY ACID
METABOLISM
 A fatty acid is a carboxylic acid.
often with a long unbranched aliphatic chain, which is either
saturated or unsaturated.
Carboxylic acids as short as butyric acid (4 carbon atoms) are
considered to be fatty acids,
Fatty acids are produced by the hydrolysis of the ester linkages in
a fat or biological oil (both of
which are triglycerides), with the
removal of glycerol.
The most abundant natural fatty acids have an even number of
carbon atoms.
Major Physiological Roles oF Fatty Acids
1. Fatty Acids (FAs) are building blocks of phospholipids and
glycolipids.
2. Many proteins are modified by the covalent attachment of
FAs, which targets them to membrane locations.
3. FAs are fuel molecules that are stored as triacylglycerols (or
triglycerides) (TGs).
4. FAs derivatives serve as hormones and intracellular
messengers
 Fatty acids are oxidized in
Fatty Acids Are
Linked to CoA
Before They Are
Oxidized
mitochondria.
 They are activated before they enter
the mitochondrial matrix.
 ATP drives the formation of a thioester
linkage between the carboxyl group
of a FA and the sulfhydryl group of
CoA.
 This activation reaction takes place on
the outer mitochondrial membrane,
where it is catalyzed by acyl CoA
synthase (also called fatty acid
thiokinase).
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1. The FA reacts with ATP to form an
acyl adenylate.
2. The sulfhydryl group of CoA then
The activation
of a fatty acid is
accomplished in
two steps:
attacks the acyl adenylate, which is
tightly bound to the enzyme, to form
acyl CoA and AMP.
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Carnitine Carries Long-Chain Activated
Fatty Acids into the Mitochondrial Matrix
 Activated long-chain FAs are transported across the
membrane by conjugating them to carnitine, a
zwitterionic alcohol.
 This reaction is catalyzed by carnitine acyltransferase I
(also called carnitine palmitoyl transferase I), bound to
the outer mitochondrial membrane.
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 Acyl carnitine is shuttled across
the inner mitochondrial
membrane by a translocase
 The acyl group is transferred
back to CoA on the matrix side
of the membrane.
 This reaction, which is
catalyzed by carnitine
acyltransferase II (carnitine
palmitoyl transferase II), is
simply the reverse of the
reaction that takes place in the
cytosol.
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 Normally, the transfer of an acyl group from an alcohol
to a sulfhydryl group is thermodynamically
unfavorable.
 However equilibrium constant for this reaction for
carnitine is near 1.
 Apparently because carnitine and its esters are
solvated differently from most other alcohols and their
esters due to the zwitterionic nature of carnitine.
 As a result, the O-acyl link in carnitine has a high
group-transfer potential.
 Finally, the translocase returns carnitine to the cytosolic
side in exchange for an incoming acyl carnitine.
 Through a sequence of
Fatty Acid
Oxidation
4 reactions:
1. Oxidation by FAD
2. Hydration by H2O
3. Oxidation by NAD+
4. Thiolysis by CoA
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1. oxidation of acyl CoA by an acyl CoA
dehydrogenase to give an enoyl CoA
with a trans C2=C3.
electron-transferring
flavoprotein
ETF:ubiquinone reductase, an
iron-sulfur protein
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2. Stereospecific hydration of the
C2=C3 by enoyl CoA hydratase.
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3. A second oxidation reaction converts
the hydroxyl group at C3 into a keto
group and generates NADH.
This oxidation is catalyzed by L-3hydroxyacyl CoA dehydrogenase,
which is specific for the L isomer of the
hydroxyacyl substrate
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4. Thiolysis of 3-ketoacyl CoA by the
thiol group of a second molecule of
CoA yields acetyl CoA and an acyl
CoA shortened by two carbon atoms.
This thiolytic cleavage is catalyzed by bketothiolase.
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 The shortened acyl CoA then
undergoes another cycle of
oxidation, starting with the
reaction catalyzed by acyl CoA
dehydrogenase
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Step
1
Reaction
Enzyme
Fatty acid + CoA + ATP
Acyl CoA synthetase [also called fatty acid
thiokinase and fatty acid:CoA ligase (AMP)]
acyl CoA + AMP + PPi
2
Carnitine + acyl CoA
3
Acyl CoA + E-FAD
trans-
Carnitine acyltransferase (also called carnitine
acyl carnitine + CoA palmitoyl transferase)
D2
-enoyl CoA + E-FADH2
Acyl CoA dehydrogenases (several isozymes having
different chain-length specificity)
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trans-D2 -Enoyl CoA +H2O
5
L-3-Hydroxyacyl CoA + NAD+
L-3-Hydroxyacyl CoA dehydrogenase
3-ketoacyl CoA + NADH + H+
6
3-ketoacyl CoA + CoA
b-Ketothiolase (also called thiolase)
acetyl CoA + acyl CoA (shortened by C2)
Enoyl CoA hydratase (also called crotonase or 3L-3-hydroxyacyl CoA hydroxyacyl CoA hydrolyase)
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CARBOHYDRATE AND
LIPID METABOLISM
CARBOHYDRATES
LIPIDS
Made of hydrogen, oxygen, and
carbon to form monosaccharides.
Made of hydrogen, oxygen, and
carbon combined into molecules
called fatty acids.
Readily combine with water
Lipids do not readily combine with
water. Some fats are solid, some are
liquids.
Glycolysis
Glycolysis
Acetyl CoA
Acetyl CoA
KETOSIS, ACIDOSIS AND
DEHYDRATION
 Normal metabolic process, something
your body does to keep working.
 When it doesn’t have enough
KETOSIS
carbohydrates from food for you cells to
burn for energy, it burns fat instead. As
part of this process it makes ketones.
 Popular weight loss strategy. Which is the
ketogenic diet.
 When our body contains too much
acid, it is known as acidosis.
 Acidosis occurs when your kidneys
ACIDOSIS
and lungs can’t keep you body’s pH
in balance.
 Your lungs and kidneys can usually
compensate for slight pH
imbalances.
CAUSES OF ACIDOSIS
RESPIRATORY ACIDOSIS
METABOLIC ACIDOSIS
Occurs when too much CO2 builds
up in the body. Normally the lungs
remove CO2 while you breathe.
This may happen due to chronic
airway conditions (asthma), injury to
the chest, obesity, sedative misuse,
overuse of alcohol, problems with
the nervous system, other chest
problems.
Starts in the kidneys instead of the
lungs.
Occurs when they can’t eliminate
enough acid or when they get rid of
too much base.
3 major forms
• Diabetic acidosis
• Hyperchloremic acidosis
• Lactic acidosis
 When your body doesn’t have as
DEHYDRATION
much water as it needs. Without
enough, your body can’t function
properly.