Topic: Lipids

Prepared by: Roy P. Maribojoc MD, MPH

Lipids
• Also known as “FATS”.
• Made of Carbon, Hydrogen and Oxygen atoms.
• Insoluble in polar solvents such as water. Their insolubility can
be attributed solely to their long hydrophobic hydrocarbon
chains.
• Lipids are hydrophobic, nonpolar molelcules.
• They are soluble in nonpolar solvent such as benzene or
chloroform.
➢ Polar molecules occur when two
atoms do not share electrons equally
in a covalent bond. A dipole forms,
with part of the molecule carrying a
slight positive charge and the other
part carrying a slight negative charge.
This happens when there is a
difference between the
electronegativity of each atom. (e.g.
water)
➢ Nonpolar molecules share electrons
equally in a covalent bond there is no
net electrical charge across the
molecule. In a nonpolar covalent bond, the electrons are evenly distributed. You can predict nonpolar
molecules will form when atoms have the same or similar electronegativity (e.g. Hydrocarbon liquids,
such as gasoline)
➢ The general rule is that "like dissolves like", which means polar molecules will dissolve into other
polar liquids and nonpolar molecules will dissolve into nonpolar liquids. This is why oil and water don't
mix: oil is nonpolar while water is polar.

Lipids are synthesized in the body using complex biosynthetic pathways. However, there are some lipids
that are considered essential and need to be supplemented in diet.

Important Functions of Lipids in the body

I. Chemical messengers

All multicellular organisms use chemical messengers to send information between organelles and to other
cells. Since lipids are small molecules insoluble in water, they are excellent candidates for signalling. The
signalling molecules further attach to the receptors on the cell surface and bring about a change that leads
to an action.

II. Storage and provision of energy

Storage lipids are triacylglycerols. These are inert and made up of three fatty acids and a glycerol. It
contains lots of energy because it is a large molecule containing multiple bonds of stored energy. Fatty acids
in non esterified form, i.e. as free (unesterified) fatty acids are released from triacylglycerols during fasting to
provide a source of energy and to form the structural components for cells.

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III. Maintenance of temperature

Layers of subcutaneous fat under the skin also help in insulation and protection from cold. Maintenance of
body temperature is mainly done by brown fat as opposed to white fat. Brown adipocytes are capable of
producing heat via a process called non-shivering thermogenesis. In this process, triglycerides are burned
into heat, thereby increasing body temperature.

Babies have a higher concentration of brown fat.

IV. Cell Membrane formation

Membrane lipids are made of polyunsaturated fatty acids. Polyunsaturated fatty acids are important as
constituents of the phospholipids, where they appear to confer several important properties to the
membranes. One of the most important properties are fluidity and flexibility of the cell membrane.

V. Cholesterol formation

1. Cholesterol is an essential structural component of animal cell membranes. Cholesterol maintains the
fluidity of membranes by interacting with their complex lipid components, specifically the phospholipids
such as phosphatidylcholine and sphingomyelin.

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Cholesterol is a lipid with a unique structure consisting of four

linked hydrocarbon rings forming the bulky steroid structure.
There is a hydrocarbon tail linked to one end of the steroid and
a hydroxyl group linked to the other end.

2. Cholesterol also serves as a precursor for the biosynthesis of bile acids, vitamin D and steroid
hormones (corticosteroids and sex steroids)

A. Bile Acids

Primary bile acids are those synthesized by the liver cells. Secondary bile acids result from bacterial
actions in the colon. Bile acids are conjugated with taurine or glycine in the liver. These conjugated bile
acids are called bile salts.

In humans, taurocholic acid and glycocholic acid (derivatives of cholic acid) and
taurochenodeoxycholic acid and glycochenodeoxycholic acid (derivatives of chenodeoxycholic acid)
are the major bile salts in bile.

❑ Bile salts act as effective emulsifying agents for fats

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 Emulsification is a process in which large lipid globules are broken down into several small lipid
globules. Though emulsification, the surface area of lipids increase over a thousand-fold, making them
more accessible to the digestive enzymes.

The main function of bile acids is to allow

digestion of dietary fats and oils by acting as a
surfactant that emulsifies them into micelles,
allowing them to be colloidally suspended in the
chyme before further processing.

Bile salts envelop the fatty acids and

monoglycerides to form micelles which allow its
transport into the cells of the intestinal wall.

Micelles are essentially small aggregates of

mixed lipids and bile acids

After being transferred across the intestinal

membrane, the fatty acids reform into triglycerides
(re-esterified), before being absorbed into the
lymphatic system through lacteals.

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 B. Vitamin D is a group of fat-soluble vitamin responsible for increasing intestinal absorption of calcium,
magnesium, and phosphate, and multiple other biological effects.

Vitamin D from the diet, or from skin synthesis, is

biologically inactive. A protein enzyme must
hydroxylate it to convert it to the active form.

This is done in the liver and in the kidneys.

Cholecalciferol (Vit D3) is converted in the liver
to calcifediol (25-hydroxyvitamin D3);
ergocalciferol (Vit D2) is converted to 25-
hydroxyvitamin D3. Calcifediol (25-
hydroxyvitamin D3) is further hydroxylated by
the kidneys to form calcitriol (also known as
1,25-dihydroxyvitamin D3), the biologically
active form of vitamin D.

Calcitriol circulates as a hormone in the blood,

having a major role regulating the concentration
of calcium and phosphate, and promoting the
healthy growth and remodeling of bone. Calcitriol
also has other effects, including some on cell
growth, neuromuscular and immune functions,
and reduction of inflammation.

It helps the body absorb calcium, which then build bones and keep bones strong and healthy. Severely low
levels of vitamin D can result in soft, brittle bones; bone pain; and muscle pain and weakness. It also helps our
immune system. Too little vitamin D results in soft bones in children (rickets) and fragile, misshapen bones
in adults (osteomalacia). It also contributes to a healthy immune system.

C. Steroid hormones Steroid hormones can be grouped into two classes:

1. Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex:

a. Glucocorticoids (example: Cortisol or hydrocortisone) affect carbohydrate, fat, and protein

metabolism, and have anti-inflammatory, immunosuppressive, anti-proliferative, and vasoconstrictive
effects.
b. Mineralocorticoids (example: aldosterone) influence salt and water balances (electrolyte balance
and fluid balance). High level of aldosterone will result to an increase blood pressure and blood
volume

2. Sex Steroids: Natural sex steroids are made mainly by the gonads (ovaries or testes). However, it
can also be synthesized by adrenal glands, or by conversion from other sex steroids in other tissue
such as liver or fat.

Sex steroids include: Estrogen, Progestogens (example: Progesterone) and Androgens

(example:Testosterone)
Sex steroids are crucial hormones for the proper development and function of the body; they regulate
sexual differentiation, the secondary sex characteristics, and sexual behavior patterns. In general,
androgens (testosterone and dihydrotestosterone or DHT) are considered "male sex hormones",
since they have masculinizing effects, while estrogens and progestogens are considered "female sex
hormones" .

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High level of Cholesterol (LDL) can lead to stroke and heart attack

Cholesterol travels through the blood on proteins called “lipoproteins.” Lipoproteins are made of fat and proteins.
Two types of lipoproteins carry cholesterol throughout the body:

• LDL (low-density lipoprotein), sometimes called “bad” cholesterol, makes up most of your body’s
cholesterol. LDL cholesterol can build up on the walls of your arteries. Hence, High levels of LDL
cholesterol raise your risk for heart disease and stroke.
• HDL (high-density lipoprotein), or “good” cholesterol, absorbs cholesterol and carries it back to the
liver. The liver then flushes it from the body. High levels of HDL cholesterol can lower your risk for
heart disease and stroke.

If your LDL cholesterol levels are too high, deposits can occur in your arteries. These fatty deposits on the walls
of your blood vessels can harden and narrow the blood vessels. This is a condition called atherosclerosis.
Narrower vessels transport less oxygen-rich blood. If oxygen can’t reach your heart muscle, you can have a
heart attack. If that happens in your brain, you can have a stroke.

Atherosclerosis:

A process of progressive thickening and hardening of the walls arteries as a result of plaque deposition
on its inner lining.

Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood. Over time, plaque
hardens and narrows your arteries. This limits the flow of oxygen-rich blood to your organs and other parts of
your body.

Risk factors for atherosclerosis include high levels of "bad" cholesterol, high blood pressure (hypertension),
smoking, diabetes and a genetic family history of atherosclerotic disease.

Atherosclerosis is responsible for much coronary artery disease (angina and heart attacks) and many strokes.

Prevention is generally by eating a healthy diet, exercising, not smoking, and maintaining a normal weight.
Treatment of established disease may include medications to lower cholesterol such as statins, blood pressure
medication, or medications that decrease clotting, such as aspirin. A number of procedures may also be carried
out such as percutaneous coronary intervention, coronary artery bypass graft, or carotid endarterectomy.

VI. Prostaglandin formation and role in inflammation

The essential fatty acids, linoleic and linolenic acids are precursors of many different types of eicosanoids,
including the hydroxyeicosatetraenes, prostanoids (prostaglandins, thromboxanes and prostacyclins),
leukotrienes (and lipoxins) and resolvins etc. these play an important role in pain, fever, inflammation and
blood clotting.

VII. Formation of "fat-soluble" vitamins

The "fat-soluble" vitamins (A, D, E and K) are essential nutrients with numerous functions.

Fat-soluble vitamins are stored in the body's cells and are not excreted as easily as water-soluble vitamins.
They do not need to be consumed as often as water-soluble vitamins, although adequate amounts are
needed. If you take too much of a fat-soluble vitamin, it could become toxic.

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Fat-soluble vitamins
Nutrient Function Sources

Vitamin A (and its Vitamin A from animal sources (retinol): fortified milk,
precursor*, beta- cheese, cream, butter, fortified margarine, eggs, liver
Needed for vision, healthy skin
carotene)
and mucous membranes, bone
Beta-carotene (from plant sources): Leafy, dark green
and tooth growth, immune system
*A precursor is vegetables; dark orange fruits (apricots, cantaloupe)
health
converted by the and vegetables (carrots, winter squash, sweet
body to the vitamin. potatoes, pumpkin)

Egg yolks, liver, fatty fish, fortified milk, fortified

Needed for proper absorption of
Vitamin D margarine. When exposed to sunlight, the skin can
calcium; stored in bones
make vitamin D.

Polyunsaturated plant oils (soybean, corn, cottonseed,

Vitamin E Antioxidant; protects cell walls safflower); leafy green vegetables; wheat germ; whole-
grain products; liver; egg yolks; nuts and seeds

Leafy green vegetables such as kale, collard greens,

and spinach; green vegetables such as broccoli,
Vitamin K Needed for proper blood clotting
Brussels sprouts, and asparagus; also produced in
intestinal tract by bacteria

Vitamin A deficiency (VAD) or hypovitaminosis A is a lack of vitamin A in blood and tissues. It is common in
poorer countries, but rarely is seen in more developed countries. Nyctalopia (night blindness) is one of the first
signs of VAD. Xerophthalmia, keratomalacia, and complete blindness can occur. VAD also diminishes the
ability to fight infections.
Xerophthalmia caused by a severe vitamin A deficiency is described by pathologic dryness of the conjunctiva
and cornea. The conjunctiva becomes dry, thick and wrinkled. If untreated, it can lead to corneal ulceration and
ultimately to blindness as a result of corneal damage..
Keratomalacia is an eye condition which manifests as cloudiness and softening of the cornea. This eye
disease often starts as xerophthalmia, which is severe dryness of the cornea and conjunctiva. If Keratomalacia
is not treated, the softening of the corneas can lead to infection, rupture, and tissue changes that may result in
blindness. Keratomalacia is also known as xerotic keratitis and corneal melting.
Vitamin A deficiency is the leading cause of preventable childhood blindness. The World Health Organization
(WHO) recommends that all children aged 6–59 months should receive supplements if they live in a community
where VAD is a public health problem. (Vit. A supplementation: 6-11 months 100,000 IU Vit A; 12-59 months
200,000 IU of Vit A given every 6 months)
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Vitamin D deficiency can lead to a loss of bone density, which can contribute to osteoporosis and fractures.

Severe vitamin D deficiency in children, it can cause rickets. Rickets is a rare disease that causes the bones to
become soft and bend. In adults, severe vitamin D deficiency leads to osteomalacia. Osteomalacia causes
weak bones, bone pain, and muscle weakness.

Vitamin E deficiency

Low levels of vitamin E can lead to:

• Muscle weakness: Vitamin E is essential to the central nervous system. It is among the body's main
antioxidants, and a deficiency results in oxidative stress, which can lead to muscle weakness.
• Coordination and walking difficulties: A deficiency can cause certain neurons, called the Purkinje
neurons, to break down, harming their ability to transmit signals.
• Numbness and tingling: Damage to nerve fibers can prevent the nerves from transmitting signals
correctly, resulting in these sensations, which are also called peripheral neuropathy.
• Vision deterioration: A vitamin E deficiency can weaken light receptors in the retina and other cells in
the eye. This can lead to loss of vision over time.
• Immune system problems: Some research suggests that a lack of vitamin E can inhibit the immune
cells. Older adults may be particularly at risk.

There are several symptoms associated with vitamin K deficiency, but the main one is excessive bleeding.
Excessive bleeding may not be immediately evident, as it may only occur if a person is cut or wounded.

Additional signs of excessive bleeding can also include:

• bruising easily
• small blood clots appearing under the nails
• bleeds in mucous membranes that line areas inside the body
• stool that is dark black, tar-like, or contains blood

When looking for signs of vitamin K deficiency in newborn babies and infants, doctors will also look for:

• bleeding from the area where the umbilical cord has been removed
• bleeding in the skin, nose, gastrointestinal tract, or other areas
• sudden brain bleeds, which are deemed severe and potentially life-threatening

Dietary fat composition: Dietary fat Composition: More than 95% are triglycerides, the other are Cholesterol,
Cholesteryl esters, Phospholipids, and Unesterified fatty acids.
◼ Triglycerides – Fats & Oils
1. Predominate form of fat in foods and major storage form of fat in the body
2. Structure – composed of 3 fatty acids + glycerol

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Glycerol 3 fatty acids

✓ Fatty Acids
o Organic acid (chain of carbons with hydrogens attached) that
has an acid group at one end & a methyl group at the other
end

Saturation
◼ Saturated fatty acid
o carbon chains filled with hydrogen atoms (no C=C double
bonds)
o Appear solid at room temperature
o Commonly found in animal fats (butter, lard) & tropical oils
(palm, coconut)

◼ Unsaturated fatty acid

o carbon chains contain at least 1 C=C double bond
o Appear liquid at room temperature
o Types:
1. Monounsaturated fat – triglyceride containing fatty acids with 1 double bond; i.e. canola
& olive oil
2. Polyunsaturated fat- triglycerides containing a high % of fatty acids with 2 or more
double bonds; i.e. corn, safflower, soybean, sunflower oils and fish;

Monounsaturated fats are “healthy fats”. In fact, the evidence shows that monounsaturated fats have a
number of health benefits. They can help with weight loss, reduce the risk of heart disease and decrease
inflammation
Saturated fats can increase the risk of heart disease and stroke by promoting the buildup of plaque in the blood
vessels, hence it is also referred to as “bad fats”

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Dietary Sources of Lipids
a. Animal Sources
Dairy products- Milk, butter, cream
Meat (pork, beef, poultry)Fish, eggs
b. Vegetable Sources
Cooking oils- Sun flower, Mustard, canola, corn olive peanut Ground nut oil
Fats from other vegetable sources (olives and avocado)

Major Enzymes of Lipid Digestion:

1. Lipases- for digestion of triglycerides (TGS)
Main lipases:
b. Lingual
c. Gastric
d. Pancreatic
Triglycerides are degraded by lipases to form free fatty acids and glycerol

2. Phospholipase A2- for digestion of phospholipids

3. Cholesterol esterase- for digestion of cholesterol

Digestion of Lipids

1. Mouth
❑ Begins in the mouth as lipids encounter saliva.
❑ Physical action of chewing coupled with the action of the lingual lipase

Lingual lipase :
▪ Secreted by dorsal surface of tongue
▪ Active at low pH (Ph2.0 -7-5)
▪ Optimum pH 4.0 -4-5
▪ Enzymatic action continue in the stomach
▪ Ideal substrate – Short chain Triglycerides (TGS)
2. Stomach
❑ Lipid digestion in the stomach is through the action of Gastric lipase and lingual lipase
❑ Requires the presence of ca++
❑ Less effective in stomach due to acidic PH
❑ Not effective for long chain fatty acids, most effective for short and medium chain fatty acid
❑ Milk, egg yolk and fats containing short chain fatty acids are suitable substrate for its action
❑ Very little fat digestion occurs in the stomach.
Role of fats in gastric emptying
❑ Fats delay the rate of emptying of stomach
❑ Action is brought about by secretion of Enterogastrone (secreted by the cells in the small
intestine)
❑ Enterogastrone inhibits gastric motility and retards the discharge of bolus of food from the
stomach.
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 ❑ Thus fats have a high satiety value
Satiety value is the degree at which food gives a human the sense of food gratification, the
exact contrast feeling of hunger. Highest satiety value is expected when the food remains in the
stomach for a longer period.

Significance of Lingual and Gastric Lipases

❑ Play important role in lipid digestion in neonates since milk is the main source of energy

❑ Important digestive enzymes in pancreatic insufficiency such as Cystic fibrosis or other pancreatic
disorders

➢ Lingual and gastric lipases can degrade triglycerides with short and medium chain fatty acids in
patients with pancreatic disorders despite a near or complete absence of pancreatic lipase

3. Digestion in small intestine

❑ Major site of fat digestion

❑ Effective digestion due to the presence of Pancreatic lipase and bile salts.

❑ Lipids are digested mainly in the small intestine by bile salts through the process of emulsification, which
allows lipases to divide lipids into fatty acids and monoglycerides.

Emulsification and digestion

❑ Lipids are hydrophobic, and thus are poorly soluble in the aqueous environment of the digestive tract.

❑ The digestive enzyme, lipase, is water soluble and can only work at the surface of fat globules.

❑ Digestion is greatly aided by emulsification, the breaking up of fat globules into much smaller emulsion
droplets.

❑ Bile salts act as effective emulsifying agents for fats

Emulsification is a process in which large lipid globules are broken down into several small lipid
globules. Though emulsification, the surface area of lipids increase over a thousand-fold, making them
more accessible to the digestive enzymes.

❑ The critical process of emulsification takes place in the duodenum.

❑ Bile salts are synthesized in the liver and stored in the gall bladder

❑ Bile salts are also required for the proper functioning of the pancreatic lipase enzyme

❑ Bile salts help in combination of lipase with two molecules of a small protein called as Colipase. This
combination enhances the lipase activity.

❑ Secretion of pancreatic juice is stimulated by-

❖ Passage of acid gastric contents in to the duodenum

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 ❖ By secretion of Secretin, Cholecystokinin and Pancreozymin, the gastro intestinal hormones

❑ Secretin- Increases the secretion of electrolytes and fluid components of pancreatic juice

❑ Pancreozymin -stimulates the secretion of the pancreatic enzymes

❑ Cholecystokinin - causes the contraction of the gall bladder and discharges the bile in to the
duodenum.

❑ Hepatocrinin- Released by intestinal mucosa, stimulates more bile

Contents of Pancreatic Juice

❑ Pancreatic Lipase- For the digestion of triglycerides

❑ Phospholipase A2- for the digestion of Phospholipids

❑ Cholesterol esterase-For the digestion of Cholesteryl esters

❑ Bile salts envelop the fatty acids and monoglycerides to form micelles.
❑ Micelles have a fatty acid core with a water-soluble exterior. This allows efficient transportation to the
intestinal microvillus where the fat components are released and disseminated into the cells of the
digestive tract lining.
❑ It is the monoglycerides and fatty acids that are absorbed into the intestinal wall (NOT the micelles)
❑ Because of their nonpolar nature, monoglycerides and fatty acids can just diffuse across the plasma
membrane of the enterocyte.

❑ Some absorption may be facilitated by specific transport proteins

4. Intestinal cells/Lining
❑ Absorption takes place through the mucosal lining of the small intestine,
❑ Once inside the cells, the free fatty acids and monoglycerides enter the endoplasmic reticulum,
❑ The monoglycerides and fatty acids reassemble themselves into triacylglycerols.
❑ Before triacylglycerols actually leave the epithelial cells, they're coated by proteins, which results
in the formation of chylomicrons.
▪ chylomicrons are small globules composed of protein and lipid; hence it is a large
lipoproteins. The coating of protein gives the triglyceride a water-soluble coat, and this
allows the chylomicron to travel outside of the cell.

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The newly formed chylomicrons leave the epithelial cell and enter the lymphatic capillaries, which are called
lacteals.

The lacteals are found in the fingerlike projections of the intestinal wall, called the villi. The lacteals represent
another unique way fats are absorbed because lipids pass through the lymphatic system before they make their
way back to your bloodstream.

❑ Chylomicrons transport food fats perfectly through the body’s water-based environment to
specific destinations such as the liver and other body tissues.
❑ If fats are not absorbed properly as is seen in some medical conditions, a person’s stool will
contain high amounts of fat also known as steatorrhea. Steatorrhea can result from diseases
that affect absorption, such as Crohn’s disease and cystic fibrosis.
o Steatorrhea (or steatorrhoea) is the presence of excess fat in feces.

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