Grasas

M.Sc. Alfonso Daniel Silva

 Sterols and steroids
Steroid nucleus
4-ring core structure
cyclopentanoperhydrophenanthrene
 Sterols and steroids

Sterols are
monohydroxy
A side chain is added to carbon 17
alcohols

They posses an OH in carbon 3

 Sterols and steroids
Cholesterol is the It can exist in free form, or the
most common hydroxyl group can be
example of sterol esterified with a fatty acid

Is present only in animal tissues

Sterols and steroids
It can exist in free form, or the
hydroxyl group can be
esterified with a fatty acid
 Sterols and steroids

Common dietary sources of cholesterol

Essential component of cell membranes (particulary

membranes of nerve tissue)
 Sterols and steroids
Cholesterol
Precursor for

Other steroids in the body

Bile acids Steroid sex hormones Adrenocortical

hormones

Estrogens Androgens Progesterone Vitamin D

 Phospholipids
Lipids containing phosphate.
 Phospholipids

If core structure is glycerol If core structure is amino alcohol

sphingosine

Glycerophosphatides
Sphingolipids

If contains sphingosine If contains sphingosine and

and phosphate carbohydrates

Sphingomyelins Cerebrosides, and gangliosides.

Sphingophosphatides Glycolipids
 Glycerophosphatides
• The building block of
a glycerophosphatide
is phosphatidic acid,
formed by
esterification of two
fatty acids at C-1 and
C-2 of glycerol and
esterification of the
C-3 hydroxyl with
phosphoric acid.
 Glycerophosphatides
• Phosphatidic acids
form a number
• of derivatives with
compounds such as
choline,
ethanolamine,
• serine, and inositol.

Common
name 
lecithin
Glycerophosphatides
 Rol of phospholipids
• Phospholipids play several important roles
in the body. Glycerophosphatides, for
example, are very important components
of cell membranes.
• In addition to lending structural support to
the membrane, they serve as a source of
physiologically active compounds
Rol of phospholipids

Is involved in regulating
transcription, mediating
immune responses, in
regulating cell growth,
and in learning and
memory
 Sphingolipids
• Sphingomyelins occur in plasma membranes of
animal cells and are found in particularly large
amounts in the myelin sheath of nerve tissues.
• Sphingomyelins are important in the nervous
system.
 Sphingolipids
• Sphingomyelins contain ceramide.

Sphingosine
+ fatty acid =
ceramide
 Glycolipids
• Glycolipids can be subclassified into
cerebrosides and gangliosides. They are
so named because they have a
carbohydrate component within their
structure.
• Like the phospholipids, their physiological
role is principally structural, contributing
little as an energy source.
 Glycolipids
• Cerebrosides and gangliosides occur in
the medullary sheaths of nerves and in
brain tissue, particularly the white matter.
• The sphingosine moiety provides the
backbone for glycolipid structure.
• It is attached to a fatty acid by an amide
bond.
Glycolipids
 Glycolipids
• Gangliosides resemble cerebrosides,
except that the single monosaccharide unit
of the cerebroside is replaced by an
oligosaccharide containing various
monosaccharide derivatives.
 Gangliosides
• They are molecules composed of
a glycosphingolipid(ceramide and oligosaccharide) with one or
more sialic acids (e.g. n-acetylneuraminic acid, NANA) linked on
the sugar chain.
 Gangliosides
• Gangliosides are known to be involved in
certain recognition events that occur at the
cell surface.
• For example, they provide the
carbohydrate determinants of the human
blood groups A, B, and O.
 Digestion
• The dietary lipid targeted for digestion is
emulsified by a very efficient process,
mediated mainly by bile salts.
• This emulsification greatly increases the
surface area of the dietary lipid targeted for
digestion.
• Consequently, the accessibility of the fat to
digestive enzymes is greatly increased by
bile salt action.
 Digestion
• Triacylglycerols, phospholipids (primarily
phosphatidylcholine), and sterols (mainly
cholesterol) provide the lipid component of
the typical Western diet.
 Digestion
• Of these, triacylglycerols, customarily called fats
or triglycerides, are by far the major contributor,
with a consumption rate of about 150 g daily on
average.
• Cholesterol intake  300-600 mg/day.
• Digestive enzymes  triacylglycerols (lipase),
phospholipids (phospholipases), cholesteryl
esters (cholesterol esterase)
 Triacylglycerol digestion
• Most dietary triacylglycerol digestion is completed in the lumen of
the small intestine, although the process actually begins in the
stomach with lingual lipase released by the serous gland, which lies
beneath the tongue, and gastric lipase produced by the main cells of
the stomach.
 Triacylglycerol digestion
• Basal secretion of these lipases apparently
occurs continuously but can be stimulated
by neural (sympathetic agonists), dietary
(high fat), and mechanical (sucking and
swallowing) factors.
• These lipases account for much of the
limited digestion (10%–30%) of TAG that
occurs in the stomach.
 Triacylglycerol digestion
• Basal secretion of these lipases apparently
occurs continuously but can be stimulated
by neural (sympathetic agonists), dietary
(high fat), and mechanical (sucking and
swallowing) factors.
• These lipases account for much of the
limited digestion (10%–30%) of TAG that
occurs in the stomach.
 Triacylglycerol digestion
• For dietary fat in the stomach to be
hydrolyzed by lingual and gastric lipases,
some degree of emulsification must occur
to expose a sufficient surface area of the
substrate.
• Muscle contractions of the stomach and the
squirting of the fat through a partially
opened pyloric sphincter produce shear
forces sufficient for emulsification
 Triacylglycerol digestion
• The partially hydrolyzed lipid emulsion
leaves the stomach and enters the
duodenum as fine lipid droplets.
• Effective emulsification takes place
because as mechanical shearing
continues, it is complemented by bile that is
released from the gallbladder as a result of
stimulation by the hormone cholecystokinin
(CCK).
Only a small percentage
of the triacylglycerols is
hydrolyzed totally to free
glycerol.
The complete hydrolysis
of triacylglycerols that
does occur probably
follows the isomerization
of the 2-
monoacylglycerol to 1-
monoacylglycerol, which
is then
hydrolyzed.
The major products of lipid digestion
enter the enterocyte by simple
diffusion across the plasma
membrane

Fatty acid transporter

protein in the membrane.
Transport and storage
 Lipoproteins
• Lipids resynthesized in the enterocytes, together
with fat soluble vitamins, are collected in the
cell’s endoplasmic reticulum as large fat
particles
 Lipoproteins
• While still in the endoplasmic reticulum, the particles
receive a layer of lipoprotein B-48 on their surface. It
stabilizes the particles in the aqueous environment of the
circulation, which they eventually enter.
 Lipoproteins
• Chylomicrons belong to a family of compounds called lipoproteins,
which get their name from the fact that they are made of lipids and
proteins. Lipoproteins play an important role in transporting lipids,
and serum lipoprotein patterns have been implicated as risk factors
in chronic cardiovascular disease.
 Lipoproteins
• The protein portion of any lipoprotein is called the apolipoprotein.
Apolipoproteins play a very important role in the structural and
functional relationship among the lipoproteins.
 Lipoproteins
• Chylomicrons transport exogenous dietary lipids. Lipoproteins other
than chylomicrons transport endogenous lipids, which are circulating
lipids that do not arise directly from intestinal absorption but instead
are processed through other tissues, such as the liver.
 Lipoproteins
• Lipoproteins with higher concentrations of lipid have a lower density.
Very low density lipoproteins (VLDLs or pre-β-lipoprotein) are made
in the liver; the primary function of these lipoproteins is to transport
triacylglycerol made by the liver to other, non-hepatic tissues.
 Lipoproteins
• As TAG is removed from these lipoproteins, they undergo a brief
stage as intermediary lipoprotein (IDL). As further TAG is removed,
IDLs become low-density lipoproteins (LDL).
 Lipoproteins
• As TAG is removed from these lipoproteins, they undergo a brief
stage as intermediary lipoprotein (IDL). As further TAG is removed,
IDLs become low-density lipoproteins (LDL).
 Lipoproteins
• In order of lowest (the most lipid) to highest density, the
lipoprotein fractions are chylomicrons, very low density
lipoproteins (VLDLs), low-density lipoproteins (LDLs),
and high-density lipoproteins (HDLs).
• An intermediate-density particle (IDL) also exists, which
has a density between that of VLDL and LDL. The IDL
particles are very short lived in the bloodstream,
however, and have little nutritional or physiological
importance.
Lipoproteins
 Apolipoproteins
• Apolipoproteins, the protein components of lipoproteins,
tend to stabilize the lipoproteins as they circulate in the
aqueous environment of the blood, but they also have
other important functions.
 Apolipoproteins
• They confer specificity on the lipoprotein complexes,
allowing them to be recognized by specific receptors on
cell surfaces. Apolipoproteins also stimulate certain
enzymatic reactions, which in turn regulate the
lipoproteins’ metabolic functions.
 Chylomicrons
• The re-formed lipid derived from exogenous sources
leaves the enterocytes (intestinal mucosal cells) largely
in the form of chylomicrons, though some HDL is
produced by the enterocytes as well.
 Chylomicrons
• Chylomicrons are one of the five major groups of lipoproteins:
chylomicrons, very low-density lipoprotein, intermediate-density
lipoprotein, low-density lipoprotein and high-density lipoprotein.
 Chylomicrons
• Chylomicrons are the primary form of lipoprotein formed from
exogenous (dietary) lipids.
• The role of the chylomicron is to deliver dietary lipid mostly to
tissues other than the liver, such as muscle and adipose tissue
(80%). Much of the lipid delivered to the liver is in the form of
chylomicron remnants (20%).
• Chylomicrons first appear in the lymphatic vessels of the abdominal
region and then enter the bloodstream at a slow rate, which
prevents large-scale changes in the lipid content of peripheral blood.
 Chylomicrons
• Entry of chylomicrons into the blood from the lymph can
continue for up to 14 hours after consumption of a large
meal rich in fat.
• The peak level of lipid in blood plasma usually occurs 30
minutes to 3 hours after a meal and returns to near
normal within 5 to 6 hours.
• This time can vary, however, depending on the stomach
emptying time, which in turn depends on the size and
composition of the meal.
 Very Low Density Lipoprotein (VLDL)
and Low-Density Lipoproteins (LDL)
• Very low density lipoproteins are produced in the liver
from endogenous triacylglycerol in much the same way
as chylomicrons were produced in the enterocytes.
• The lipid is synthesized in the smooth ER, transferred to
the Golgi apparatus, and excreted from the cell along
with the apolipoproteins B-100, apoC, and apoE.
 Very Low Density Lipoprotein (VLDL)
and Low-Density Lipoproteins (LDL)
• Nascent VLDL of liver origin is stripped of triacylglycerol
by lipoprotein lipase at extracellular sites, resulting in the
formation of a transient IDL particle and, finally, a
cholesterol-rich LDL.
• Within the muscle cell, the free fatty acids from VLDL
and those derived from hydrolysis of the absorbed
diacylglycerols are primarily oxidized for energy, with
only limited amounts resynthesized for storage as
triacylglycerols.
• Endurance-trained muscle, however, does contain
triacylglycerol deposits.
Very Low Density Lipoprotein (VLDL)
and Low-Density Lipoproteins (LDL)
Very Low Density Lipoprotein (VLDL)
and Low-Density Lipoproteins (LDL)
Very Low Density Lipoprotein (VLDL)
and Low-Density Lipoproteins (LDL)
Very Low Density Lipoprotein (VLDL)
and Low-Density Lipoproteins (LDL)
Very Low Density Lipoprotein (VLDL)
and Low-Density Lipoproteins (LDL)
Very Low Density Lipoprotein (VLDL)
and Low-Density Lipoproteins (LDL)
 Role of the liver and adipose tissue
in lipid metabolism
• Our normal eating pattern is to consume a
meal, followed by several hours of fasting
before we eat again.
• Our bodies have adapted to cope with the
time of extra nutrients in the blood
followed by a period in which the levels of
blood nutrients must be restored from
tissue storage.
 Liver
• Hepatic synthesis of the bile salts, indispensable
for digesting and absorbing dietary lipids, is one
of its functions.
• The liver is capable of synthesizing new lipids
from nonlipid precursors, such as glucose and
amino acids.
• It can also take up and catabolize exogenous
lipids delivered to it in the form of chylomicron
remnants, repackaging their lipids into HDL and
VLDL forms.
 Liver
• In the postprandial (fed) state, glucose, amino
acid, and short-chain fatty acid concentrations
rise in portal blood, which goes directly to the
liver.
• In the hepatocyte, glucose is phosphorylated for
use, and glycogen subsequently is synthesized
until the hepatic glycogen stores are repleted.
• If portal hyperglycemia persists (more glucose
comes from the digestive system), glucose is
converted to fatty acids.
 Liver
• In addition to the newly synthesized lipid derived
from nonlipid precursors, there is also the
exogenous lipid delivered to the liver, derived
from chylomicron remnants and short-chain fatty
acids that were excreted from the intestine
directly into the portal blood.
• The apolipoprotein E on the surface of the
chylomicron remnants binds with specific
receptors for apoE in the vascular endothelial
cells of the liver.
 Liver
• The lipid portion of the chylomicron remnant is
hydrolyzed and absorbed into the hepatocyte as
free fatty acids, monoacylglycerols,
diacylglycerols, glycerol, and cholesterol.
• Exogenous free fatty acids of short-chain length
delivered directly to the hepatic tissue can be
used for energy or, following chain elongation, to
resynthesize other lipid fractions.
 Liver
• Chylomicron remnant cholesterol and cholesteryl
esters may be used in several ways:
• converted to bile salts and secreted in the
bile
• secreted into the bile as neutral sterol (such
as cholesterol or cholesteryl ester)
• incorporated into VLDL or HDL and released
into the plasma
 Liver
• Because triacylglycerols can be formed from
glucose, hepatic triacylglycerol production is
accelerated when the diet is rich in carbohydrate.
• The HDL are involved in reverse cholesterol
transport and, when synthesized in the liver, are
smaller than the VLDL and contain less
triacylglycerol.
• HDL also possesses phospholipids and cholesterol
in addition to TAG as its major lipid constituents.
 Adipose tissue
• Unlike the liver, adipose is not involved in
the uptake of chylomicron remnants or the
synthesis of endogenous lipoproteins.
• Adipose is involved in absorbing TAG and
cholesterol from chylomicrons through the
action of lipoprotein lipase. Adipocytes are
the major storage site for triacylglycerol.
Liver
 Adipose tissue
• As in the liver, adipocyte triacylglycerol
can be synthesized from glucose, a
process strongly influenced by insulin.
• Insulin accelerates the entry of glucose
into the adipose cells (the liver does not
respond to this action of insulin).
 Metabolism of triacylglycerol
during fasting
• In the fasting state, the metabolic scheme in these
tissues shifts.
• As blood glucose levels diminish, insulin
concentration falls, accelerating lipolytic activity in
adipose tissue. The lipolytic activity produces free
fatty acids and glycerol.
• Free fatty acids derived from adipose tissue
circulate in the plasma in association with albumin
and are taken up by the liver or muscle cells and
oxidized for energy by way of acetyl CoA formation.
 Metabolism of triacylglycerol
during fasting
• In the liver, some of the acetyl CoA is diverted to
produce ketone bodies, which can serve as
important energy sources for muscle tissue and
the brain during fasting and starvation.
• The liver continues synthesizing VLDL and HDL
and releases them into circulation, though these
processes are diminished in a fasting situation.