1. Lipids of Physiological Significance
By Dr. Reem Sallam

2. Objectives To know what is the definition of lipids
To understand the major functions of lipids
To know the basic structure of FA
To understand the difference between saturated and unsaturated FA
To be familiar with some examples of FA of physiologic importance
To know the essential FAs
Reem Sallam, MD, PhD

3. Objectives, continued…
To understand the nature, types, and use of KBs
To understand the mechanism of diabetic ketoacidosis (DKA)
To know the different categories of complex lipids (phospholipids, glycolipids)
To be introduced briefly to some of the medical application of lipids of physiological significance
To know the difference between different lipoprotein particles.
Reem Sallam, MD, PhD

4. What are lipids? What are their main functions?

5. They can be extracted from tissues by nonpolar solvents.
Lipids are heterogeneous group of H2O-insoluble (hydrophobic) organic molecules.
They can be extracted from tissues by nonpolar solvents.
In the body, they are generally compartmentalized, or transported in plasma in association with protein (albumin), or as lipoproteins.
Reem Sallam, MD, PhD

6. Reem Sallam, MD, PhD

7. Functions of lipids: Main source of energy
Provide hydrophobic barrier (partitioning)
Special functions:
Regulatory or coenzyme function (fat-soluble vitamins)
Control of body homeostasis ( PGs & steroid hormones)
Reem Sallam, MD, PhD

8. Fatty Acids

9. Structure of FAs
pKa 4.8
Predominant in LCFAs
Reem Sallam, MD, PhD

10. FA Free (unesterified) fatty acids (FFA, low levels in tissues)
Esterified (fatty acyl esters) in:
TAG CE PL
In Plasma FA are either:
Esterified
>90% of FA in plasma
Contained in LP particles
FFA
Carried by albumin
Their levels can be v high (e.g in fasting)
Are on their way from their origin (TAG of AT or circulating LP) to their target (tissues) to perform various functions
Reem Sallam, MD, PhD

11. Functions of FA
When oxidized (by many tissues, especially liver & muscle)  energy
Structural components of membrane lipids (e.g PL & GL)
When attached to certain intracellular protein  the ability of proteins to associate w/ membranes
Precursors of hormone-like PG (Arachidonic acid)
Storage form of fuel (TAG in AT)
Reem Sallam, MD, PhD

12. Saturated vs Unsaturated FA
Saturated = No DB
Unsaturated = DB
DB nearly always cis
DB are 3-C intervals
DB:  ↓Tm  ↑ fluid nature
FA chain length  ↑Tm 
↓ fluid nature
The presence of DB in the LCFA in membrane  maintain the fluid nature of membrane lipids
kink (bend)
Reem Sallam, MD, PhD

13. Examples of physiologically important FA
20 carbons
4 DB
Reem Sallam, MD, PhD

14. Essential FA Dietary essential in human Linoleic acid -Linolenic acid
If deficient in diet (rare condition)  scaly dermatitis, visual & neurologic abnormalities)
Linoleic acid
18:2(9,12)
-6 FA
The precursor of arachidonic acid (the substrate of PG synthesis)
-Linolenic acid
18:3(9,12,15)
-3 FA
The precursor of other -3 FA important for growth & development
Reem Sallam, MD, PhD

15. Arachidonic acid as an -6 FA
Is only essential if linoleic acid is deficient in the diet.
Reem Sallam, MD, PhD

16. Prostaglandins

17. Oxidation & Cyclization of arachidonic acid by PG endoperoxide synthase

18. TriAcylGlycerol (TAG)

19. Acylglycerol Fat Oil solid @ RT liquid @ RT kink (bend)
TAG = Neutral Fat
Saturated or Unsaturated
Typically saturated
Typically unsaturated
Reem Sallam, MD, PhD

20. Storage of TAG The 1ary site of TAG synthesis is the liver
TAG are only slightly soluble in H2O
TAG coalesce within adipocytes  cytosolic oily droplets (nearly anhydrous; the major energy reserve of the body)
Reem Sallam, MD, PhD

21. Ketone Bodies

22. What are KBs?
* mitochondrial

23. KB: An alternate fuel for cells
Organic acids
Soluble in aqueous solution; no special carrier is needed (LP nor albumin)
Either
functional (metabolized: Acetoacetate,  (or 3)-OH butyrate) or
non metabolized side product : Acetone: volatile  can be released in the breath.
Transported in blood to the peripheral tissues.
In peripheral tissues (extra-hepatic: sk. M., ♥ m., renal cortex, brain) they are converted to Ac. CoA
Ac. CoA can be oxidized (TCA)  Energy
Produced by liver (when the [Ac. CoA] > liver capacity to oxidize Ac. CoA
Their use is  [KB] in blood
If blood [KB] ↑ enough, they pass BBB  used by the brain for energy production (KB spare Glc)
Reem Sallam, MD, PhD

24. Steroids

25. Cholesterol & Cholesterol ester
Reem Sallam, MD, PhD

27. Complex Lipid

28. Phospholipids

29. What are phospholipids?
Polar, ionic, amphipathic
Composed of
an alcohol,
DAG or sphingosine

30. What are the functions of PL?
Phospholipids
What are the functions of PL?
The predominant lipids in cell membranes
Reservoir for intracellular messengers
Anchors of some proteins to cell membranes
Component of lung surfactant
Components of bile (detergent property  solubilization of cholesterol)

31. Phopholipids A- Glycerophospholipids PA + Ser = PS
PA + EA = PE: cephalin
PA + C = PC: lecithin
PA + I = PI
PA + Glycerol = PG
Plasmalogens & PAF
2 PA + Glycerol = Cardiolipin (diphosphotidylglycerol)

32. Phopholipids B- Sphingophospholipids: sphingomyelin
Sphingosine (an amino alcohol) + LCFA = Ceramide
Ceramide + Phosphoryl Choline = Sphingomyelin
Sphingomyelin is an important constituent of the myelin of nerve fibers in CNS

33. Role of PC in lung surfactant
Dipalmitoyl-phosphatidylcholine (DPPC), made & secreted b type II pneumocytes is the major lipid component of lung surfactant.
Lung surfactant is the extracellular fluid layer lining the alveoli
Surfactant is a complex mixture of lipids (90%), & proteins (10%), DPPC is the major component to ↓ the surface tension (ST) of this fluid layer  preventing alveolar collapse (atelectasis)
~ 32 weeks of gestation there is a major shift from Sphingomyelin (S) to Lecithin (L; DPPC) synthesis in the pneumocytes of the fetus.
L/S in amniotic fluid  2 is evidence of maturity.

34. Infantile Respiratory distress syndrome (RDS)
RDS in preterm infants is associated with insufficient surfactant production &/or secretion
RDS is a major cause of all neonatal deaths in Western countries.
Can we accelerate lung maturation? Yes.
giving the mother glucocorticoids shortly before delivery
natural or synthetic surfactant (by intratracheal instillation; preventive & therapeutic in infant with RDS)

35. Adult Respiratory distress syndrome
In adult whose surfactant-producing pneumocytes have been damaged or destroyed (e.g. by infection or trauma)

36. Role of phosphatidylinositol (PI) in signal transmission across membranes

37. PIP2

39. Glycolipids

40. Types of Glycosphingolipids:
Neutral glycosphingolipids: cerebrosides (mainly present in the brain & peripheral nervous tissue
Acidic glycosphingolipids:
Gangliosides (contains NANA; sialic acid)
Medical importance: several lipid storage disorders involve the accumulation of NANA-containing glycosphingolipids in cells (e.g.Tay-Sachs disease, Fabry disease, Gaucher disease, Niemann-Pick disease)
Sulfatides: sulfoglycosphingolipids:
cerebrosides containing S-Gal, found predominantly in nerve tissue & kidney

41. Neutral glycosphingolipid (glalactocerbroside)

42. Acidic Glycosphingolipids Galactocerebroside 3-S

43. Acidic Glycosphingolipids Ganglioside GM2

44. Serum Lipoproteins; size & density
Bad Cholesterol
Good Cholesterol