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;
(2) convert nutrient molecules into the cell’s own
characteristic molecules, including precursors of
METABOLIS macromolecules;
M (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 chemical
transformations taking place in a cell or
METABOLIS organism, occurs through a series of
M enzyme-catalyzed 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 source
GLYCEROL of energy, glycerol and fatty acids are
METABOLIS released into the bloodstream.
M  In some organisms, the glycerol
component can enter glycolysis pathway
directly and thus provide energy for
cellular metabolism.
  The glycerol hydrolyzed from fats or
complex lipids can also be a rich energy
source. The first step in glycerol
GLYCEROL
utilization is an activation step.
METABOLIS
M  The body uses one ATP molecule to
form glycerol 1-phosphate, which is the
same as glycerol 3-phosphate:
 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 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.
Fatty Acids Are  This activation reaction takes place on the
Linked to CoA outer mitochondrial membrane, where it is
Before They Are catalyzed by acyl CoA synthase (also called
Oxidized 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 attacks the acyl adenylate, which is
of a fatty acid tightly bound to the enzyme, to form
is acyl CoA and AMP.
accomplished
in two steps:

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 16

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 4
reactions:
1. Oxidation by FAD
Fatty Acid 2. Hydration by H2O
Oxidation
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 ETF:ubiquinone reductase, an

flavoprotein 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-3-

hydroxyacyl 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 b-

ketothiolase.

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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 Reaction Enzyme
1 Fatty acid + CoA + ATP   Acyl CoA synthetase [also called fatty acid
acyl CoA + AMP + PPi thiokinase and fatty acid:CoA ligase (AMP)]
2 Carnitine + acyl CoA   Carnitine acyltransferase (also called carnitine
acyl carnitine + CoA palmitoyl transferase)
3 Acyl CoA + E-FAD Acyl CoA dehydrogenases (several isozymes having
trans- D2 -enoyl CoA + E-FADH2 different chain-length specificity)
4 trans-D2 -Enoyl CoA +H2O Enoyl CoA hydratase (also called crotonase or 3-
L-3-hydroxyacyl CoA hydroxyacyl CoA hydrolyase)
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 C 2)

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CARBOHYDRATE
AND LIPID
METABOLISM
 CARBOHYDRATES LIPIDS
Made of hydrogen, oxygen, and carbon to Made of hydrogen, oxygen, and carbon
form monosaccharides. 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 carbohydrates
from food for you cells to burn for energy, it
KETOSIS 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 and
ACIDOSIS 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
DEHYDRATI  When your body doesn’t have as much
water as it needs. Without enough, your
ON body can’t function properly.