LIPIDS AND ITS

METABOLISM

LIPIDS
Compound that insoluble in water

but soluble in polar solvents.

Also known as FATS AND OIL .
CLASSIFIED INTO TWO GENERAL
TYPES
FATS AND WAXES ( can be
hydrolyzed with ester linkages)
CHOLESTEROLS AND STEROIDS
( cannot be hydrolyzed).

TYPES OF LIPIDS
SATURATED FATS
Animal oil like meat, milk ,butter.
Vegetable oil like coconut and palm kernel oil.
POLYUNSATURATED FATS
Plan source like safflower , corn, cottonseed,

sunflower oil, and soybean oil.

MONOUNSATURATED FAT
Plants and animals product like olive oil,
canola oil, avocado and peanut oil.

FUNCTIONS OF LIPIDS
Excellent energy reserves
Stucture of cell membrane
Body thermal insulations
Essential fatty acids ( EFA)
Hormone synthesis
Fat soluble vitamin absorption

LIPID STRUCTURE

LIPIDS DISORDERS
LIPIDS DEFICIENCY (Shortage in

Lipids intake)
LIPIDS EXCEEDING (Overtaking in
Lipids intake)

LIPIDS DEFICIENCY
Fat should comprise of 3% of total calories

to prevent fatty acid deficiency

Fatty acid deficiency syndromes
Dry scaly skin, dermatitis (Linoleic acid

deficiency)
Hand tremors (Prostaglandin deficiency)
Inability to control blood pressure

LIPIDS EXCEEDING
Fat should comprise not more than

30% of total calories to prevent lipids

exceeding
To prevent overtaking, we should
consume fat breakdown (% total
calories)
<8% from saturated fat
10% from polyunsaturated fat
10-15% from monounsaturated fat

BLOOD LEVELS OF LIPIDS

Total Cholesterol:
<200 mg/dl = desirable
200-239 mg/dl = borderline
hyperlipidemia
>240 mg/dl = hyperlipidemia
LDL < 130 mg/dl is favorable
HDL > 35 mg/dl

OVERVIEW IN LIPID
METABOLISM
The major aspects of lipid

metabolism are involved with

Fatty Acid Oxidationto
produce energy or the
synthesis of lipids which is
calledLipogenesis. Lipid
metabolism is closely
connected to the metabolism
of carbohydrates which may
be converted to fats. This can
be seen in the diagram on the
left. The metabolism of both is
upset by diabetes mellitus.

The first step in lipid metabolism is the

hydrolysis of the lipid in the cytoplasm to
produce glycerol and fatty acids.
Since glycerol is a three carbon alcohol, it is
metabolized quite readily into an intermediate
in glycolysis, dihydroxyacetone phosphate.
The last reaction is readily reversible if
glycerol is needed for the synthesis of a lipid.
The hydroxyacetone, obtained from glycerol is
metabolized into one of two possible
compounds. Dihydroxyacetone may be
converted into pyruvic acid through the
glycolysispathway to make energy.

The hydroxyacetone, obtained from glycerol is

metabolized into one of two possible
compounds. Dihydroxyacetone may be
converted into pyruvic acid through the
glycolysispathway to make energy.
In addition, the dihydroxyacetone may also be used
ingluconeogenesisto make glucose-6phosphate for glucose to the blood or glycogen
depending upon what is required at that time.

Fatty acids are oxidized to acetyl CoA

in the mitochondria using the
fatty acid spiral. The acetyl CoA is
then ultimately converted into ATP,
CO2, and H2O using the
citric acid cycleand the
electron transport chain.

Fatty acids are synthesized from

carbohydrates and occasionally from
proteins. Actually, the carbohydrates
and proteins have first been
catabolized into acetyl CoA. Depending
upon the energy requirements, the
acetyl CoA enters the citric acid cycle
or is used to synthesize fatty acids in a
process known as LIPOGENESIS

CHOLESTEROL
Plant and animal food contain

sterols but only animal food

contain cholesterol
Why? Cholesterol is made in the
liver and plants do no have a
liver
Cholesterol is needed to make
bile, sex hormones, steroids and
vitamin D.
It is the constituent of cell
membrane structure
Dietary recommendation - <300
mg/d
Sources egg yolks, liver,
shellfish, organ foods

NORMAL CHOLESTEROL
METABOLISM
Key concepts: synthesis
Primary synthetic sites are extrahepatic, but

liver is key regulator of homeostasis

Key concepts: absorption
Largest source is biliary secretion, not diet.
Normal absorption: 50%
For cholesterol to be absorbed it must:
undergo hydrolysis (de-esterification by esterases)
be incorporated into micelles
be taken up by cholesterol transporter
be re-esterified and incorporated into chylomicrons

NORMAL CHOLESTEROL
METABOLISM
Role of Bile Salts, cholesterol, phospholipids in gall

stone formation.
Importance of Bile Salts for cholesterol absorption
Key concepts: bile salt absorption

inhibitors
Bile acid binding compounds:
Welchol
Cholestyramine
Colestipol
Fiber

Surgery: Partial ileal bypass.

NORMAL TRIGLYCERIDE
METABOLISM
Key concepts: absorption
Triglyceride (i.e. energy) assimilation is key to

the survival of the organism.

Dietary triglyceride must be hydrolyzed to fatty
acids, mono-glycerides and glycerol prior to
absorption.
Fatty acids must partition to micellar phase for
absorption.
For transport, triglyceride must be reconstituted
from glycerol and fatty acid and incorporated
into chylomicrons.

LIPOPROTEIN
Low Density Lipoproteins (LDL) is made

by the liver and is comprised of

cholesterol that is delivered to the cells in
the body
High levels of LDL is strongly correlated
with heart disease
High Density Lipoproteins (HDL) - made
by the liver and picks up cholesterol from
the cells fro recycling or excretion
High levels of HDL is inversely
correlated with heart disease
It is protective

LIPOPROTEIN

An atherogenic lipoprotein
containing apo(a) and apoB.
Apo(a)
20-30% of people have levels
suggesting C-V risk.
LDL
Black subjects have Lp(a)
-S-Snormal range twice as high
as white and Asiatic subjects.
Apo(a) sequence similar to plasminogen, and Lp(a)
interferes with spontaneous thrombolysis.
Lp(a) levels highly genetic, resistant to diet and drug
therapy, although niacin may help.

LIPOPROTEIN
METABOLISM

THE FOUR MAJOR LIPOPROTEIN

CLASSES

Lipoproteins:
Separation by
Electrophoresis

Density

Size by
Electron Microscopy

DISTRIBUTION OF LIPOPROTEINS
ALONG A DENSITY

APOLIPOPROTEINS
apoA-I
apoA-II
apoA-IV
apoB100
apoB-48
apoC-I

HDL structural protein; LCAT

activator;RCT
HL activation
Tg metabolism; LCAT activator; diet
response protein of all LP except HDL
Structural
Binding to LDL receptor

apoC-II

Inhibit Lp binding to LDL R; LCAT

activator
LpL activator

apoC-III

LpL inhibitor; antagonizes apoE

apoE

B/E receptor ligand

Responsivity

*E2:IDL; *E4: Diet

PREVENTION OF LIPID
DISORDERS
Reduce fat
Cut down on high fat foods
E.g. butter, margarine, oil,

mayonnaise
Consume small amounts of

unsaturated fats
Do not eliminate fat completely

since it is high in calories

PREVENTION OF LIPID
DISORDERS
Limit added sugar and alcohol
Added sugar and alcohol are

empty calories
Watch portions of all food
fat free calorie-free

Drink at least 8 glasses of water

everyday
Water is calorie-free, refreshing,

and filling

PREVENTION OF LIPID
DISORDERS
Increase intake of

vegetables, fruits, and whole

grains
Loaded with fiber
Contain high amounts of

vitamins, minerals, and

phytonutrients
Include low-fat protein-rich

food with every meal

DIGESTION OF LIPIDS
1. Emulsification of Fats
Fatty acids can be liberated by simple

hydrolysis of the ester bonds

in triglycerides, but the insolubility of the
triglycerides presents a problem; digestion
occurs following dispersion of dietary fat
into small particles with sufficiently
exposed

DIGESTION OF LIPIDS
surface area for rapid attack by digestive

enzymes. This is achieved by detergent

action
and mechanical mixing, with the detergent
effect being supplied by several components,
both in the diet and in the digestive juices,
but especially by partially digested fats (fatty
acid soaps and monacylglycerols) and by bile
salts.

DIGESTION OF LIPIDS
The bile salts such as cholic acid contain a
hydrophobic side and a
hydrophilic side, thus allowing bile salts to dissolve
at an oil-water interface, with the
hydrophobic surface in contact with the nonpolar
phase and the hydrophilic surface in the
aqueous medium. This detergent action emulsifies
fats and yields mixed micelles,
which allow attack by water-soluble digestive
enzymes and facilitate the absorption of
lipids through the intestinal mucosa.

DIGESTION OF LIPIDS
Mixed Micelles also serve as transport vehicles
for those lipids that are less water-soluble than
fatty acids, such as cholesterol or the
fat-soluble vitamins A, D, E, and K. Thus,
efficient absorption of lipids depends on the
presence of sufficient bile acids to solubilize the
ingested lipids.

Categories of lipids
Fatty acids
Glycerolipids
Glycerophospholipids
Sphingolipids
Sterol lipids
Prenol lipids
Saccharolipids

FATTY ACIDS
Fatty acidsor fatty acid residues when they form part

of a lipid, are a diverse group of molecules

synthesized by chain-elongation of anacetylCoAprimer withmalonyl-CoAor methylmalonyl-CoA
groups in a process calledfatty acid synthesis.They
are made of ahydrocarbon chainthat terminates with
acarboxylic acidgroup; this arrangement confers the
molecule with apolar,hydrophilicend, and a
nonpolar,hydrophobicend that isinsolublein water.
The fatty acid structure is one of the most
fundamental categories of biological lipids, and is
commonly used as a building-block of more
structurally complex lipids.

FATTY ACIDS
. The carbon chain, typically between four and 24 carbons

long,may be saturated orunsaturated, and may be attached

tofunctional groupscontainingoxygen,halogens,nitrogen,
andsulfur. If a fatty acid contains a double bond, there is the
possibility of either acisortransgeometric isomerism, which
significantly affects the molecule'sconfiguration.Cis-double
bonds cause the fatty acid chain to bend, an effect that is
compounded with more double bonds in the chain. Three
double bonds in 18-carbonlinolenic acid, the most abundant
fatty-acyl chains of plantthylakoid membranes, render these
membranes highlyfluiddespite environmental lowtemperatures,and also makes linolenic acid give dominating
sharp peaks in high resolution 13-C NMR spectra of
chloroplasts. This in turn plays an important role in the
structure and function of cell membranes.Most naturally
occurring fatty acids are of thecisconfiguration, although
thetransform does exist in some natural and partially
hydrogenated fats and oil.

GLYCEROPHOSPOLIPIDS
Glycerophospholipids, usually referred to

asphospholipids, are ubiquitous in nature and are key

components of thelipid bilayerof cells,as well as
being involved inmetabolism andcell
signaling.Neural tissue (including the brain) contains
relatively high amounts of glycerophospholipids, and
alterations in their composition has been implicated in
various neurological disorders.[Glycerophospholipids
may be subdivided into distinct classes, based on the
nature of the polar headgroup at thesn-3 position of
the glycerol backbone ineukaryotesand eubacteria,
or thesn-1 position in the case ofarchaebacteria.

SPHINGOLIPIDS
Sphingolipidsare a complicated family of

compounds]that share a common structural feature,

asphingoid basebackbone that is synthesizedde
novofrom the amino acid serineand a long-chain
fatty acyl CoA, then converted intoceramides,
phosphosphingolipids, glycosphingolipids and other
compounds. The major sphingoid base of mammals is
commonly referred to assphingosine. Ceramides (Nacyl-sphingoid bases) are a major subclass of
sphingoid base derivatives with anamide-linked fatty
acid. The fatty acids are typically saturated or monounsaturated with chain lengths from 16 to 26 carbon
atoms.

STEROL LIPIDS
Sterol lipids, such ascholesteroland its derivatives,
are an important component of membrane
lipids,along with the glycerophospholipids and
sphingomyelins. Thesteroids, all derived from the
same fused four-ring core structure, have different
biological roles ashormonesandsignaling
molecules. The eighteen-carbon (C18) steroids
include the estrogenfamily whereas the C19
steroids comprise theandrogenssuch
astestosteroneandandrosterone. The C21
subclass includes theprogestogensas well as
theglucocorticoidsandmineralocorticoids.

STEROL LIPIDS
Thesecosteroids, comprising various forms

ofvitamin D, are characterized by cleavage of

the B ring of the core structure.Other
examples ofsterolsare thebile acidsand
their conjugates,which in mammals are
oxidized derivatives of cholesterol and are
synthesized in the liver. The plant equivalents
are thephytosterols, such assitosterol,stigmasterol, andbrassicasterol;
the latter compound is also used as
abiomarkerforalgalgrowth.The predominant
sterol infungalcell membranes isergosterol.

PHENOL LIPIDS
Prenollipids are synthesized from the five-carbon-

unit precursorsisopentenyl
diphosphateanddimethylallyl diphosphatethat
are produced mainly via themevalonic acid(MVA)
pathway.The simple isoprenoids (linear alcohols,
diphosphates, etc.) are formed by the successive
addition of C5 units, and are classified according
to number of these terpeneunits. Structures
containing greater than 40 carbons are known as
polyterpenes.Carotenoidsare important simple
isoprenoids that function asantioxidantsand as
precursors ofvitamin A.

PHENOL LIPIDS
Another biologically important class of

molecules is exemplified by
thequinonesandhydroquinones, which
contain an isoprenoid tail attached to a
quinonoid core of non-isoprenoid
origin.]Vitamin E andvitamin K, as well as
theubiquinones, are examples of this class.
Prokaryotes synthesize polyprenols (called
bactoprenols) in which the terminal isoprenoid
unit attached to oxygen remains unsaturated,
whereas in animal polyprenols (dolichols) the
terminal isoprenoid is reduced

SACCHAROLIPIDS
Saccharolipids describe compounds in which fatty

acids are linked directly to a sugar backbone,

forming structures that are compatible with
membrane bilayers. In the saccharolipids,
amonosaccharidesubstitutes for the glycerol
backbone present in glycerolipids and
glycerophospholipids. The most familiar
saccharolipids are the
acylatedglucosamineprecursors of the
LipidAcomponent of
thelipopolysaccharidesinGram-negative
bacteria

SACCHAROLIPIDS
Typical lipidA molecules

aredisaccharidesof glucosamine, which

are derivatized with as many as seven
fatty-acyl chains. The minimal
lipopolysaccharide required for growth inE.
coliis Kdo2-Lipid A, a hexa-acylated
disaccharide of glucosamine that is
glycosylated with two 3-deoxy-D-mannooctulosonic acid (Kdo) residues.

PROJECT IN BIOCHEMISTRY
PREPARED BY :
DREZA MAE A. DOMINGO
EARL VAN ERIC GILTENDEZ
BS PHARMACY ll
SUBMITTED TO :
SIR. JORGE PETER A. TINAYA RPh.