Lipids: Vital Components in Health and Disease.pdf

Lipids: Vital Components in Health and Disease

Lipids, commonly known as fats, are crucial molecules that play multiple roles in the human body. This presentation will delve into the types and functions of lipids, including their role in energy storage, cellular structure, and hormone production. For BSc Nursing students, understanding lipids is essential for patient care, particularly in managing conditions like cardiovascular disease, obesity, and malnutrition. We will also discuss dietary sources of lipids, their metabolism, and the impact of lipid imbalances on health. This knowledge is vital for promoting proper nutrition and advising patients on healthy lifestyle choices.

1. Unit-II Lipids

2. Lipids
•Lipidsmay be defined as compounds which are relatively insoluble
in water, but freely soluble in non-polar organic solvents, such as
benzene, chloroform, ether, hot alcohol, acetone, etc.
•Storageform of energy (triacylglycerol)
•Structural components of biomembranes (phospholipids and cholesterol)
•Metabolic regulators (steroid hormones and prostaglandins)
•Act as electric insulators in neurons
•Provide insulationagainst changes in external temperature (subcutaneous
fat)
•Give shape and contour to the body
•Protect internal organs by providing a cushioning effect (pads of fat)
•Help in absorption of fat soluble vitamins(A, D, E and K)

3. CLASSIFICATION OF LIPIDS
•Based on the chemical nature, lipids are classified as:
1.Simple lipids: They are esters of fatty acids with glycerol or other
higher alcohols.

4. 2.Compound/complex lipids: They are fatty acids esterified with
alcohol; but in addition they contain other groups.
I.Phospholipids, containing phosphoric acid.
II.Non-phosphorylated lipids.
•Glycolipids
•Lipoproteins
phospholipid
Phospholipid and non-phosphorylated lipid

5. 3.Derived lipids: They are compounds, which are derived from lipids
or precursors of lipids, e.g. fatty acids, steroids and cholesterol.
Cholesterol

6. Fatty Acids
•Fatty acids are carboxylic acids with hydrocarbon side chain.
•R-COOH
•They are the simplest form of lipids.
1.Straight chain fatty acids
•Saturated fatty acid
•Even carbon acids - e.g., palmitic acid and stearic acid
•Odd carbon acids – e.g., propionic acid
•Unsaturated fatty acid
•Mono Unsaturated fatty acid (MUFA) – e.g., oleic acid and palmitoleic acid
•Poly Unsaturated fatty acid (PUFA) – e.g., linoleic acid, linolenic acid, arachidonic acid
2.Branched fatty acids- e.g.,isovaleric acid less abundant in plants and
animals.
3.Substituted fatty acids – hydrogen replaced with another group, lactic
acid of blood, cerebronic acid and oxynervonic acids of brain glycolipids.
4.Cyclic fatty acids- bacteria and seed lipids

7. Functions of fatty acids
•Major fuel – stored in adipose tissues
•Building blocks of phospholipids and glycolipids
•Building blocks of biological membranes
•Derivatives serves as
•hormones
•Prostaglandins
•Intracellular messengers
•phosphatidylinositol

8. Clinical significance of MUFA
•Source: animal and plant based foods (olive oil, nuts and seeds)
•Reduce blood cholesterol and TGL, blood pressure and heart disease risk.
•Diet increases good cholesterol (HDL)
•Reduce risk of certain cancers
•Improve insulin sensitivity and blood sugar control.

9. Clinical significance of PUFA
•Source: soybean, corn, walnuts, tofu, soybean and sunflower
•Reduce risk of heart disease and stroke.
•Contribute vit. E to the diet.

10. Essential Fatty acids
•The fatty acids that cannot be synthesized by the body and, therefore,
should be supplied in the diet are known as essential fatty acids
(EFA).
•Chemically, they are polyunsaturated fatty acids, namely linoleic acid
(18 : 2; 9, 12) and linolenic acid (18 : 3; 9, 12, 15).
•Arachidonic acid (20 : 4; 5, 8, 11, 14) becomes essential, if its
precursor linoleic acid is not provided in the diet in sufficient
amounts.
•Biochemical basis for essentiality: Linoleic acid and linolenic acid are
essential since humans lack the enzymes that can introduce double
bonds beyond carbons 9 to 10.

11. Clinical Significance of EFA
•Proper development and functioning of the brain and nervous
system.
•Formation of healthy cell membrane.
•Regulation of blood clotting.
•Transport and breakdown of cholesterol.
•Skin and hair protection.

12. •The deficiency of EFA results in phrynoderma
or toad skin, characterized by the presence of
horny eruptions on the posterior and lateral
parts of limbs, on the back and buttocks, loss of
hair and poor wound healing.
Deficiency of EFA

13. TRANS FATTY ACIDS (TFA)
•Unsaturated fatty acids
•They are present in diary products and in hydrogenated edible oils.
•Generally considered to be injurious to health.
•Used in food industry to increase the shelf life of the fried food.
•TFA affects multiple risk factors for chronic diseases, including
composition of blood lipids and lipoproteins, systemic inflammation,
endothelial dysfunction, insulin resistance, diabetes and adiposity.
•It is high in processed foods and bakery products, where partially
hydrogenated veg. oils are used for cooking.
•Compete with essential fatty acids, causes essential fatty acid deficiency.
•Raise LDL, TAG, and lower HDL.

14. Digestion of Lipids
•Stomach
•Lingual lipase (2.5-5 pH)
•Gastric lipase (5.4 pH)
•Intestine
•Bile salts (detergent action)
•Peristalsis (mechanical mixing)
•Phospholipids.
•Lipolytic enzymes in intestines
•Pancreatic lipase with co-lipase
•Cholesterol esterase
•Phospholipase A2
Short Chain triglycerides
(milk butter ghee)
Emulsification- dispersion of lipids into
smaller droplets

15. Digestion of triacylglycerols
(fat)
Pancreatic lipase
Triacylglycerol 2-monoacylglycerol + 2 fatty acid

16. •Cholesteryl esters

17. •Phospholipids -> free fatty acid and a lysophospholipid by
phospholipase A2

18. Absorption- of lipids
•The primary products obtained from the lipid digestion are 2-
monoacylglycerol, free fatty acids and free cholesterol.
•Micelles formation diffuse through plasma membrane by diffusion.

19. •Resynthesized lipids are
put together as lipid
droplets by a thin layer of
apolipoprotein (A and B48)
and phospholipids called
chylomicrons.

20. •The presence of chylomicrons (Greek: chylos– juice)
gives the lymph a milky appearance, which is
observed after a lipid-rich meal.
•Chylomicrons enter the large body veins via the
thoracic duct.
•Blood from here flows to the heart and then to the
peripheral tissues (muscle, adipose tissue) and,
finally, to the liver.
•Adipose tissue and muscle take up a large proportion
of dietary lipids from chylomicrons for storage and
transport.
•It is believed that this bypass arrangement (passage
of chylomicrons through peripheral tissues) protects
the liver from a lipid overload after a meal.

21. Abnormalities in Absorption of Lipids
1.Defective digestion: In steatorrhea, daily excretion of fat in feces is
more than 6 g per day.
•In pancreatic deficiency: Steatorrhea; unsplit fat is present in stools
•When bile is not available: Absorption is defective; split fat is present in
stools; defective absorption of vitamin K leads to prolonged prothrombin
time.
2.Defective absorption: On the other hand, if the absorption alone is
defective, most of the fat in feces may be split fat, i.e. fatty acids
and monoglycerides. Defective absorption may be due to diseases:
•Celiac disease, sprue, Crohn's disease.
•Surgical removal of intestine.
•Obstruction of bile duct:

22. Metabolism of Lipids
Fate of glycerol : The adipose tissue lacks the enzyme glycerol
kinase, hence glycerol produced in lipolysis cannot be
phosphorylated here.
It is transported to liver where it is activated to glycerol 3-
phosphate. The latter may be used for the synthesis of
triacylglycerols and phospholipids.
Glycerol 3-phosphate may also enter glycolysis by getting
converted to dihydroxyacetone phosphate

23. Mobilization of fat from adipose tissue

24. FATTY ACID OXIDATION
•The fatty acids in the body are mostly oxidized by β-oxidation.
•β-Oxidation may be defined as the oxidation of fatty acids on the β -
carbon atom.
•This results in the sequential removal of a two carbon fragment,
acetyl CoA.

25. •The β-oxidation of fatty acids involves three stages
I.Activation of fatty acids occurring in the cytosol
II.Transport of fatty acids into mitochondria
III.β-Oxidation in the mitochondrial matrix.
•Fatty acids are oxidized by most of the tissues in the body.
•However, brain, erythrocytes and adrenal medulla cannot utilize fatty
acids for energy requirement.

26. Activation of fatty acids (cytosol)
•Fatty acids are activated to acyl CoA by thiokinases or acyl CoA
synthetases.
•The reaction occurs in two steps and requires ATP, coenzyme A
and Mg2+.
•Fatty acid reacts with ATP to form acyladenylate which then
combines with coenzyme A to produce acyl CoA.
•In the activation, two high energy phosphates are utilized ,
since ATP is converted to pyrophosphate (PPi).
•The enzyme inorganic pyrophosphatase hydrolyses PPi to
phosphate (Pi).
•The immediate elimination of PPi makes this reaction totally
irreversible.
•Three different thiokinases, to activate long chain (10-20
carbon), medium chain (4-12carbon) and short chain (< 4
carbon) fatty acids have been identified.

27. Transport of acyl CoA into mitochondria

28. β-Oxidation proper
1.Oxidation
2.Hydration
3.Oxidation
4.Cleavage

30. Sudden infant death syndrome
•It is now estimated that at least 10% of SIDS is due to deficiency of medium
chain acyl CoA dehydrogenase.
•The enzyme defect has a frequency of 1 in 10,000 births and is, in fact,
more prevalent than phenylketonuria.
•Glucose is the principal source of energy, soon after eating or feeding
babies.
•After a few hours, the glucose level and its utilization decrease and the rate
of fatty acid oxidation must simultaneously increase to meet the energy
needs.
•The sudden death in infants is due to a blockade in β-oxidation caused by a
deficiency in medium chain acyl CoA dehydrogenase (MCAD).

31. Jamaican vomiting sickness
•This disease is characterized by severe
hypoglycemia, vomiting, convulsions, coma
and death.
•It is caused by eating unripe ackee fruit which
contains an unusual toxic amino acid,
hypoglycin A.
•This inhibits the enzyme acyl CoA
dehydrogenase and thus β-oxidation of fatty
acids is blocked, leading to various
complications.

32. KETONE BODIES
•The compounds namely acetone, aceto-acetate and β-
hydroxybutyrate (or 3-hydroxy-butyrate) are known as ketone bodies.
•Only the first two are true ketones while β-hydroxybutyrate does
not possess a keto (C=O)group.
•Ketone bodies are water-soluble and energy yielding.
•Acetone, however, is an exception, since it cannot be metabolized.

33. Ketogenesis
•The synthesis of ketone bodies occurs in the liver.
•The enzymes for ketone body synthesis are located in
the mitochondrial matrix.
•Acetyl CoA, formed by oxidation of fatty acids,
pyruvate or some amino acids, is the precursor for
ketone bodies.

34. Ketolysis
•The ketone bodies are utilized by extrahepatic tissues.
•The heart muscle and renal cortex prefer the ketone bodies to glucose as fuel.
•Tissues like skeletal muscle and brain can also utilize the ketone bodies as
alternate sources of energy, if glucose is not available.
•Acetoacetate is activated to acetoacetyl CoA by thiophorase enzyme.
•Almost all tissues and cell types can use ketone bodies as fuel, with the exception
of liver and RBC.
•The placenta can use ketone body as fuel. Intestinal mucosal cells, brain and
adipocytes use ketone bodies. Skeletal muscles, heart, liver, etc. primarily utilize
fatty acids during starvation.
•Then acetoacetyl CoA enters the beta oxidation pathway to produce energy.

35. KETOSIS
•Normally the rate of synthesis of ketone bodies by the liver is such
that they can be easily metabolized by the extrahepatic tissues.
Hence, the blood level of ketone bodies is less than 1 mg/dL and only
traces are excreted in urine (not detectable by usual tests).
•But when the rate of synthesis exceeds the ability of extrahepatic
tissues to utilize them, there will be accumulation of ketone bodies in
blood.
•This leads to ketonemia, excretion in urine (ketonuria) and smell of
acetone in breath. All these three together constitute the condition
known as ketosis.

36. Causes for Ketosis
1.Diabetes mellitus: Untreated diabetes mellitus is the most common
cause for ketosis.
•Even though glucose is in plenty, the deficiency of insulin causes accelerated lipolysis
and more fatty acids are released into circulation.
•Oxidation of these fatty acids increases the acetyl CoA pool.
•Enhanced gluconeogenesis restricts the oxidation of acetyl CoA by TCA cycle, since
availability of oxaloacetate is less.
2.Starvation: In starvation, the dietary supply of glucose is decreased.
•The increased rate of lipolysis is to provide alternate source of fuel.
•The excess acetyl CoA is converted to ketone bodies.
•The high glucagon favors ketogenesis.
•The brain derives 75% of energy from ketone bodies under conditions of fasting.
•Hyperemesis (vomiting) in early pregnancy may also lead to starvation-like condition
and may lead to ketosis.

37. Salient Features of Ketosis
1.Metabolic acidosis. Acetoacetate and beta-hydroxy butyrate are acids. When
they accumulate, metabolic acidosis results.
2.Reduced buffers. The plasma bicarbonate is used up for buffering of these
acids.
3.Kussmaul's respiration. Patients will have typical acidotic breathing due to
compensatory hyperventilation.
4.Smell of acetone in patient's breath.
5.Osmotic diuresis induced by ketonuria may lead to dehydration.
6.Sodium loss. The ketone bodies are excreted in urine as their sodium salt,
leading to loss of cations from the body.
7.Dehydration. The sodium loss further aggravates the dehydration.
8.Coma. Hypokalemia, dehydration and acidosis are contributing for the lethal
effect of ketosis.

38. Cholesterol
•The level of cholesterol in blood is related to the development of
atherosclerosis and myocardial infarction.
•Abnormality of cholesterol metabolism may lead to cardiovascular
accidents and heart attacks.

39. Functions of cholesterol
•Cell membranes: Cholesterol is a component of membranes and has a
modulating effect on the fluid state of the membrane.
•Nerve conduction: Cholesterol is used to insulate nerve fibers.
•Bile acids and bile salts are derived from cholesterol. Bile salts are
important for fat absorption.
•Steroid hormones: Glucocorticoids, androgens and estrogens are from
cholesterol.
•Vitamin D3 is from 7-dehydro-cholesterol.
•Esterification: The OH group of cholesterol is esterified to fatty acids to
form cholesterol esters. This esterification occurs in the body by transfer of
a PUFA moiety by lecithin cholesterol acyl transferase.

40. Structure
1.All steroids have
cyclopentanoperhydrophenanthrene ring
system. It is a fused ring system made up
of 3 cyclohexane rings. The six-membered
rings are in a phenanthrene arrangement.
2.Total 27 carbon atoms.
3.One hydroxyl group at third position
which is characteristic of all sterols.
4.Double bond between carbon atoms 5
and 6.
5.An eight carbon beta oriented side chain
attached to 17th carbon.

41. CHOLESTEROL BIOSYNTHESIS
1.Synthesis of HMG CoA
2.Formation of mevalonate (6C)
3.Production of isoprenoid units (5C)
4.Synthesis of squalene (30C)
5.Conversion of squalene to cholesterol (27C).

42. Regulation of cholesterol synthesis

43. Degradation of cholesterol`
•Cholesterol cannot be metabolized in humans.
•Cholesterol (50%) is converted to bile acids, excreted in feces, serves
as a precursor of steroid hormones, vitamin D.

44. Liver and Cholesterol
•The liver has a major role in controlling the plasma levels of LDL
cholesterol.
1.Liver synthesizes cholesterol
2.Liver removes cholesterol from LP remnants.
3.Liver is the only organ that can excrete cholesterol through bile.
4.Liver converts cholesterol to bile acids.

45. Plasma Cholesterol-biomedical importance
•Total plasma cholesterol 150-200mg/dl
•Hypercholesterolemia
•Diabetes mellitus
• Hypothyroidism (myxoedema)
•Obstructive jaundice
•Nephrotic syndrome
•Hypocholesterolemia
•A decrease in the plasma cholesterol, although less common, is also
observed.
•Hyperthyroidism, pernicious anemia, malabsorption syndrome, hemolytic
jaundice etc., are some of the disorders associated with hypocholesterolemia.

46. LIPOPROTEINS
•Lipoproteins are molecular complexes that consist of lipids and
proteins (conjugated proteins).
•They function as transport vehicles for lipids in blood plasma.
•Lipoproteins deliver the lipid components (cholesterol, triacylglycerol
etc.) to various tissues for utilization.

48. Classification of lipoproteins
1. Chylomicrons : They are synthesized in the intestine and transport
exogenous (dietary) triacylglycerol to various tissues.
•They consist of highest (99%) quantity of lipid and lowest (1%)
concentration of protein. The chylomicrons are the least in density
and the largest in size, among the lipoproteins.
Function
•Chylomicrons are the transport form of dietary triglycerides from
intestines to the adipose tissue for storage; and to muscle or heart for
their energy needs.

49. …
2. Very low density lipoproteins (VLDL) :They are produced in liver and
intestine and are responsible for the transport of endogenously
synthesized triacylglycerols.
Function
•The VLDL carries triglycerols (endogenous triglycerols) from liver to
peripheral tissues for energy needs.

50. …
3. Low density lipoproteins (LDL) : They are formed from VLDL in the
blood circulation. They transport cholesterol from liver to other tissues.
•About 75% of the plasma cholesterol is incorporated into the LDL
particles.

51. …
4. High density lipoproteins (HDL) : They are mostly synthesized in
liver. Three different fractions of HDL (1, 2 and 3) can be identified by
ultracentrifugation. HDL particles transport cholesterol from peripheral
tissues to liver (reverse cholesterol transport).
•Functions of HDL
I.HDL is the main transport form of cholesterol from peripheral tissue to
liver, which is later excreted through bile. This is called reverse cholesterol
transport by HDL.
II.The only excretory route of cholesterol from the body is the bile.
III.Excretion of cholesterol needs prior esterification with PUFA. Thus PUFA
will help in lowering of cholesterol in the body, and so PUFA is anti-
atherogenic.

52. …
5. Free fatty acids—albumin : Free fatty acids in the circulation are in a
bound form to albumin. Each molecule of albumin can hold about 20-
30 molecules of free fatty acids. This lipoprotein cannot be separated
by electrophoresis.

53. Arthrosclerosis
•Atherosclerosis (Greek: athere—mush) is a complex disease characterized
by thickening or hardening of arteries due to the accumulation of lipids
(particularly cholesterol, free, and esterified) collagen, fibrous tissue,
proteoglycans, calcium deposits etc. in the inner arterial wall.
•Atherosclerosis is a progressive disorder that narrows and ultimately blocks
the arteries.
•Infarction is the term used to indicate the stoppage of blood flow resulting
in the death of affected tissue.
•Coronary arteries —the arteries supplying blood to heart—are the most
commonly affected leading to myocardial infarction or heart attacks.

54. Atherosclerosis and LDL
•Stage I: Formation of foam cells:
•Increased levels of cholesterol for prolonged periods will favour deposits in the
subintimal region of arteries.
•Aorta, coronary arteries and cerebral vessels are predominantly affected by the
atherosclerotic process.
•The LDL cholesterol, especially oxidized LDL particles are deposited in the walls
of arteries.
•Plasma LDL is mainly catabolized via apo-B LDL receptor pathway.
•But a small part of LDL particles are degraded by nonspecific uptake of
macrophages.
•Free radical induced oxidative damage of LDL will accelerate this process.
•Later, the macrophages become overloaded with cholesterol, and these are then
called “foam cells”.
•These form the hallmark of atherosclerotic plaques.

55. Stage II: Progression of atherosclerosis:
•Smooth muscle cells containing lipid droplets are seen in the lesion.
•During early stages of atherosclerosis, the condition is reversible if
plasma lipid levels, especially LDL-cholesterol levels are lowered.
•But when lipid accumulates, the lesion progresses unchecked and the
arterial changes become irreversible.

56. Stage III: Fibrous proliferation:
•Due to liberation of various growth factors by macrophages and
platelets.
•Lipoproteins, glycosaminoglycans and collagen are accumulated.
•Thus there is a definite component of inflammation in
atherosclerosis.
•This chronic inflammation leads to increased plasma high sensitive C-
reactive protein (hs-CRP).

57. Stage IV: Advancing fibrous plaque:
•This leads to narrowing of vessel
wall when proliferative changes
occur. The blood flow through the
narrow lumen is more turbulent
and there is tendency for clot
formation.

58. PLASMA LIPID PROFILE
•The sample of serum should be taken after 12–14 hours
•of fasting. In laboratories, lipid profile is assessed by
•estimating the following fractions in plasma.
1.Total cholesterol
2.HDL-cholesterol
3.LDL-cholesterol
4.Triglycerides
•In special cases, the following apoproteins are also estimated.
1.Apo-B level
2.Apo-A-I level
3.Lp(a) level

59. When should check lipid profile?
•Suspected cardiovascular disease, coronary artery disease and
peripheral vascular disease
•All patients with diabetes mellitus, atleast once in 6 months.
•Thyroid, liver and renal diseases, where lipid metabolism may be
altered.
•All persons above 40, should be checked once in a year.