structure and function of lipids

OS 201: Correlative Human Cell BiologyOS 201: Correlative Human Cell Biology

Monday

I. Overview of LipidsA. Major CharacteristicsB. FunctionsC. Classification of Lipids

1. Simple Lipids2. Compound (or Complex) Lipids3. Precursor and Derived Lipids4. Steroid Lipids5. Miscellaneous Lipids

II. Fatty Acid (FA)A. Characteristics and StructureB. FunctionsC. Classification of FA

1. According to Chain Length2. According to Bond Type3. According to Source

D. Nomenclature and Common NotationsE. Other Matters

III. Triacylglycerol (TAG)A. Characteristics, Functions and TypesB. Structure

IV. PhospholipidA. Characteristics and Functions B. Glycerophospholipid C. Sphingolipids

V. GlycolipidA. Characteristics, Structure, and FunctionsB. Major Glycolipids in the Body

VI. CholesterolA. Characteristics, Structure, and FunctionsB. Phase Transition Temperature

VII. SummaryVIII. Attachment

I. Overview of LIPIDS

One of the four major groups of biomolecules Unlike proteins, nucleic acids, lipids refer to a

group of heterogeneous (no common structural unit) molecules unified by common chemical features.

Similar to carbohydrates, lipids are non-informational molecules

A. General Characteristics All lipids are:

1. insoluble in water;2. soluble in nonpolar solvents like ether,

benzene, chloroform, etc.; and3. present in biological systems

B. Functions

1. storage of excess energy (e.g. FAs in TAGs)

2. major source of caloric energy (e.g. FAs in TAGs can be hydrolyzed and mobilized for catabolism)

3. thermal insulation (e.g. adipose tissues in subcutaneous tissues) and thermal insulation (e.g. nonpolar lipids act as electrical insulators, allowing rapid propagation of depolarization waves along myelinated nerves)

4. cell membrane components (e.g. phospholipids, glycolipids, cholesterol)

5. lipoproteins (e.g. fat transporters like high density and low-density lipoproteins = HDL and LDL)

6. essential for normal growth and function (e.g. DHA, docosahexaenoic acid, for brain development)

7. precursors of hormones, coenzymes and chemical mediators like your lipid-soluble vitamins (A, D, E, K); the prostaglandins (mediators of inflammatory and anaphylactic reactions), the thromboxanes (mediators of vasoconstriction) and the prostacyclins (active in the resolution phase of inflammation.)

8. bioeffectors/bioregulators (e.g. phosphatidylinositol can act as a secondary messenger)

9. Others: In small quantities, lipids are present as enzyme cofactors in electron carriers, as light absorbing pigments, as fat soluble vitamins (terpenes), as intracellular messengers, as hydrophobic anchors, etc.

C. Classification of Lipids

1. Simple lipids: Esters of fatty acids with various alcohols.

a. Fats: Esters of fatty acids with glycerol = acyl glycerols or glycerides; depending on the no. of esterified FA: mono-/di-/triacylglycerols. Oils are fats in the liquid state.

b. Waxes: Esters of fatty acids with higher molecular weight monohydric alcohols.

2. Compound (or Complex) lipids: Esters of fatty acids containing groups in addition to an alcohol and a fatty acid.

a. Phospholipids: Lipids containing, in addition to fatty acids and an alcohol, a phosphoric acid residue. They frequently have nitrogen containing bases and other substituents,

eg, in glycerophospholipids the alcohol is glycerol and in sphingophospholipids the alcohol is sphingosine.

b. Glycolipids (glycosphingolipids): Lipids containing a fatty acid, sphingosine, and carbohydrate.

3. Derived lipids: These include by-products of metabolic processes like fatty acids, glycerol, mono- and diacylglycerols, lysophosphatides, fatty aldehydes, ketone bodies.

4. Steroid Lipids: cholesterol, cholesteryl esters, cholesterol derivatives: bile acids, steroid hormones, vitamin D, phytosterols

**Because they are uncharged, acylglycerols (= glycerides), cholesterol, and cholesteryl esters are termed neutral lipids.

5. Miscellaneous Lipids: aliphatic hydrocarbons, carotenoids, squalene, terpenes (composed of isoprene units), vitamin E and K, glycerol ether, glycosyl glycerols (in plants)

July 20, 20092014 of 7 Mau, Jean, Alphius, Bryan

Prof. Milagros Leaño

Lecture # 3 – Structures and Functions Structures and Functions of Lipidsof Lipids

Exam 1


http://en.wikipedia.org/wiki/Prostaglandin

http://en.wikipedia.org/wiki/Prostacyclin

http://en.wikipedia.org/wiki/Vasoconstrictor

http://en.wikipedia.org/wiki/Thromboxane

http://en.wikipedia.org/wiki/Anaphylaxis

http://en.wikipedia.org/wiki/Inflammation


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IN FOCUS: Principal classes of STORAGE (triacylglycerols or triglycerides) and MEMBRANE LIPIDS, phospholipids, glycolipids and cholesterol. (see attachment; Fig. 1)

II. Fatty Acid

A. Characteristics and Structure1. A carboxylic acid with long chain hydrocarbon

side chain: where R = aliphatic (acyclic) hydrocarbon

s

i

d

e

c

h

a

i

n

2. usually biosynthesized by the concatenation or linking of 2 carbon units (acetyl CoA )

3. rarely found free in nature but occur in esterified form as the major components of various lipids.

B. Functions1. fuel energy2. maintenance of membrane fluidity 3. component of food oils (coconut oil, etc.)4. growth and dev’t (essential fatty acids)5. precursor of long-chain polyunsaturated fatty

acids (PUFAs) like arachidonic acid

C. Classification1. According to chain length (no. of methylene

groups or no. of carbon atoms)

a. Short chain – 2-5 C atomsb. Medium chain – 6-12 C atomsc. Long Chain – up to 25 C atoms

2. According to bond type a. Saturated FAs

– alkyl side chain contain only single bonds;

– exists in different conformations due to the complete freedom of rotation of the C-C bond ∴ flexible conformation

– extended conformation is most stable

b. Unsaturated FAs– alkyl side chain contain single and

double bonds– cis-trans isomerism exists; – double bonds along the side chain

produce “kinks” w/c contribute to fluidity and permeability.

– kinks prevent efficient packing (weakening hydrophobic interaction; thus, an unsat’d FA has a lower

melting temperature than its sat’d counterpart

– is further classified to: Monounsaturated (monoethenoid,

monoenoic) acids, containing one double bond.

Polyunsaturated (polyethenoid, polyenoic) acids, containing two or more double bonds.

3. According to sourcea. Non-essential fatty acids

– can be synthesized by the body (e.g. palmitic acid, and other saturated and monoenoic FAs)

b. Essential fatty acids – must be obtained from exogenous

sources (a.k.a. diet); humans lack the anabolic enzymes (desaturases that add a double bond in the w3 and w6 positions) that can synthesize FA with a double bond beyond C-9 (>D9)

– include your polyunsaturated fatty acids (PUFAs): linoleic, linolenic and arachidonic acids.

D. Nomenclature and Common Notations

1. Common and Systematic Names: see attachment; Table 1

2. Delta (Δ) Notation: x:y(Δm,n,…) x = no. C atoms; y = no. of double bonds;

the positions of any double bonds are specified by superscript (m,n,…) numbers following Δ (delta).

E.g. a 18-carbon FA w/ one double bond between C-9 and C-10 (C-1 being the carboxyl carbon, C in COOH) & another bet. C-12 and C-13 is designated

18:2(Δ9,12).

3. Omega (ω) Notation Recall: The carbon atoms adjacent to the

carboxyl carbon (Nos. 2, 3, and 4) are also known as the α, β, and γ carbons, respectively, and the terminal methyl carbon (farthest from COOH) is known as the ω or n-carbon.

E.g. ω9 indicates a double bond on the ninth carbon counting from the ω-carbon.

In animals, additional double bonds are introduced only between the existing double bond (e.g. ω9, ω6, or ω3) and the carboxyl carbon, leading to three series of fatty acids known as the ω9, ω6, and ω3 [omega] families, respectively.

For the essential fatty acids:Linoleic acid 18:2(Δ9,12) 18ω6

Linolenic acid 18:3(Δ9,12,15) 18ω3Arachidonic acid 20:4(Δ5,8,11,14) 20ω6Docosahexaenoic




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Fig. 2 Linoleic Acid


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acid (DHA) 22:6(Δ4,7,10,13,16,19) 22ω6

E. Other Matters

1.Why are essential fatty acids important?

EFAs are directly associated with many life-sustaining biological functions:

maintenance of healthy cell membranes growth requirement for healthy skin (prevents dermatitis, dry

flaky skin) (omega-6) precursor of long chain polyunsaturated fatty

acids, PUFAs (fr. omega fatty acids) for brain dev’t (omega-3) visual acuity/retinal dev’t (omega-3)

EFAs are precursors of eicosanoids, w/c are signaling molecules made by oxygenation of twenty-carbon essential fatty acids, (EFAs)

e.g. Prostaglandins & Thromboxanes– regulate inflammatory response– produce pain– induce sleep– reproduction– regulate blood coagulation

Leukotrienes– muscle contractant properties– chemotactic properties– important in allergic reactions

and inflammation

2.More about DHA (Docosahexaenoic acid)

Dietary sources: marine animals and planktons, moss, ferns, seed oils (rapeseed, soya, walnut)

accumulates in the 3rd trimester of pregnancy

plays an important role in brain dev’t and in visual acuity or retinal dev’t

supplemented in infant milk formulation DHA & EPA – antiatheromatous effect:

– lower LDL-cholesterol, triglycerides– competes with AA as cyclooxygenase

substrate, lowers thromboxane production, dec. platelet aggregation

– associated with lower incidence of atherosclerosis & CVD (cardiovascular disease)

3.Trans Unsaturated Fatty Acids: Good or Bad?

Present in: margarine, breads, chips, fries, breast milk, shortening

Produced by the partial hydrogenation of unsat’d FAs. by the microorganisms in the GI tract of cattle

Hydrogenation is done commercially to increase the melting point of cis-unsat’d lipids, w/c makes them attractive for baking and extends their shelf-life. However, the process frequently has a side effect that turns some cis-isomers into trans-unsaturated fats instead of hydrogenating them completely.

Adverse Health Effects:

– essential fatty acid balance and growth in infants

– high maternal intake inhibits low-chain PUFA production necessary for fetal growth and dev’t, visual and CNS dev’t

– The human lipase enzyme is ineffective with the trans configuration, so trans fat remains in the blood stream for a much longer period of time and is more prone to arterial deposition and subsequent plaque formation.

– Unlike other dietary fats, trans fats are not essential; raise levels of "bad" LDL cholesterol and lowering levels of "good" HDL cholesterol.

– increases risk for CVD, cardiovascular diseases.

III. Triacylglycerol (also called Triglyceride)

A. Characteristics, Types and Functions1. nonpolar, hydrophobic & water-insoluble = lipid2. energy reservoir in animals (stored in reduced

and anhydrous form in the adipocytes); major storage lipid: 3 FAs can be esterified to the glycerol (= efficient packing).

3. energy source: FAs can be hydrolyzed, mobilized and catabolized if needed by the body.

4. Can be simple: composed only of one kind of fatty acid; or mixed: composed of more than one type of FA.

B. Structure

+ R1–COOH + R2–COOH+ R3–COOH

Basic structure of triacylglycerol (if R1=R2=R3 simple TAG)

1-Stearoyl, 2-linoleoyl, 3-palmitoyl glycerol, a mixed triacylglycerol

IV. Phospholipid

A. Characteristics and Functions Amphipathic lipids with nonpolar aliphatic ‘tails’

and polar phosphoryl-X ‘head’. Amphiphilic or amphipatic property governs lipid

aggregation into higher order structure:

– spontaneous self assembly and self sealing– principle behind the formation of amphipathic

lipid aggregates in water: micelles (transport of bile acids), liposomes




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Liposome

http://en.wikipedia.org/wiki/High-density_lipoprotein

http://en.wikipedia.org/wiki/Low-density_lipoprotein

http://en.wikipedia.org/wiki/Essential_fatty_acid

http://en.wikipedia.org/wiki/Essential_fatty_acid

http://en.wikipedia.org/wiki/Oxygenation

http://en.wikipedia.org/wiki/Lipid_signaling


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(transport of drugs) and bilayers (membranes)

Major types of phospholipids: glycerophospholipids and sphingolipids

Functions:– major components of cell membranes and

found in most tissues (e.g. phosphatidylethanolamine = cephalin and phosphatidylserine)

– bioeffectors (phosphatidylinositol, etc.)

Phosphatidylinositols in cellular regulation.Phosphatidylinositol 4,5-bisphosphate in the plasma membrane is hydrolyzed by a specific phospholipase C in response to hormonal signals. Both products of hydrolysis act as intracellular messengers.

– lung surfactant, maintains normal lung function (e.g. Dipalmitoyl lecithin = dipalmitoyl phosphatidylcholine)

– detergent properties help solubilize cholesterol

– donors of arachidonic acid for the synthesis of prostaglandins, thromboxanes and leukotrienes

B. Glycerophospholipid

1. also called phosphoglycerides2. membrane lipids in which two FAs are attached

in ester linkage to the first and second carbons of glycerol, and a highly polar or charged group

is attached through a phosphodiester linkage to the third carbon ∴ structural backbone: phosphatidic acid

3. Phospholipids may be regarded as derivatives

of phosphatidic, in which the phosphate is esterified with the –OH of a suitable alcohol.

Doodle Space:

C. Sphingolipid (~Sphingomyelins)

Sphingomyelins are found in large quantities in brain and nerve tissue. On hydrolysis, the sphingomyelins yield a fatty acid, phosphoric acid, choline, and a complex amino alcohol, sphingosine. No glycerol is present.

The combination of sphingosine plus fatty acid is known as ceramide, a structure also found in the glycosphingolipids (also in glycolipids)

General Structure:

V. Glycolipid




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Micelle Bilayer

Aqueous cavity


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A. Characteristics, Structure and Functions

1. Glycolipids are widely distributed in every tissue of the body, particularly in nervous tissue such as brain. They occur particularly in the outer leaflet of the plasma membrane, where they contribute to cell surface carbohydrates:

cell adhesion and cell recognition; some are antigens (e.g. ABO blood group substances); some are receptors for bacterial toxins

2. Structure: Lipids containing a fatty acid (FA) +

sphingosine (= ceramide), and one or more carbohydrate.

Their backbone is either sphingosine or dihydrosphingosine, both are complex amino alcohols

Fatty acids attach to the amino group instead of attaching to the –OH group.

B. Major Glycolipids in the Body

1. Cerebrosides the simplest glycosphingolipid in the body contains ceramide (FA + sphingosine) and

a single sugar residue (the head group) contains either glucose

(glucosylcerebroside or GlcCer) or galactose (galactosylcerebroside or GalCer)

GalCer major lipid of myelin; GlcCer major glycosphingolipid of

extraneural tissues but also present in small amounts in the brain; and precursor of most of the more complex glycosphingolipids

2. Sulfatides (Sulfogalactosylceramides) C3 sulfated cerebroside (specifically, a

galactosylcerebroside) or a cerebroside 3-sulfate

It is present in high amounts in myelin Present in early stages of Alzheimer’s disease and

associated with Metachromic Leukodystrophy.

3. Globoside Cerebroside + 2 or more sugars N-acetylgalactosamine as its side chain If globosides accumulate, Sandhoff disease may occur

4. Gangliosides complex glycosphingolipids derived from

glucosylceramide that contain in addition one or more molecules of sialic acid

(ceramides + oligosaccharide + at least sialic acid)

most common and principal sialic acid found in human tissues is n-acetylneuraminic acid or NeuAc or NANA

at least 60 gangliosides are known (differ mainly in the position and number of NeuAc)

Main functions include the following:o complex CHO group; receptor for

certain pituitary glycoprotein hormoneso bacterial protein toxin receptoro cell to cell recognitiono associated with Tay-Sachs disease

Gangliosides with one NeuAc: GM3, GM2, GM1 (G represents ganglioside, M is a monosialo-containing species, and subscript is a number assigned on the basis of chromatographic migration)

GM3 = [5-acetyl-alpha-neuraminic acid] + [beta-D-galactopyranose] + [beta-D-glucopyranose] + ceramide

GM2 = GM3 + [N-acetyl-beta-D-galactopyranose]

GM2 accumulation in nerve cells of brain and other tissues is associate with Tay-Sachs disease and Sandhoff disease

GM1 = GM2 + [beta-D-galactopyranose] GM1 is an important receptor in human

intestine for cholera toxin; GM2 for C. botulinum toxin

VI. Cholesterol

A. Characteristics, Structure, and Functions

the major sterol in the body (sterol = compound has one or more hydroxyl or –OH group and no carbonyl or carboxyl group)




Exam 1



Monday

hydrophobic but with –OH group widely distributed in all cells of the body but

particularly in nervous tissue major constituent of plasma membrane and of

plasma lipoproteins precursors of bile acids, steroid hormones

(adrenocortical and sex hormones), & vit. D often found as cholesteryl ester (-OH group on

position 3 is esterified with a long-chain FA) occurs in animals but not in plants or bacteria with a steroid (cyclic) nucleus (derivative of

cyclopentanoperhydrophenanthrene ring) that resembles a phenanthrene to which a cyclopentane ring is attached.

has a planar confirmation It acts as a stabilizer by modifying membrane

fluidity (i.e. phase transition temperature)

B. Phase transition temperature (Tm)(Some explanations are obtained from Harper’s Illustrated Biochemistry, 27e – actually, similar din ng explanation ni Dr. Leano)

it is the temperature at which the structure undergoes the transition from ordered to disordered (i.e. melting)

the longer and more saturated fatty acid chains interact more strongly with each other via their long hydrocarbon chains, the higher the value of Tm (i.e. higher temperatures are required to increase the fluidity of the bilayer)

on the other hand, unsaturated bonds that exist in the cis configuration tend to increase the fluidity of a bilayer by decreasing the compactness of the side chain packing without diminishing hydrophobicity.

below Tm: increased fluidity (cholesterol interferes with interaction of hydrocarbon tails of FAs)

above Tm: limited fluidity (cholesterol limits disorder); more rigid than the hydrocarbon tails of the FAs and cannot move in the membrane to the same extent

at high cholesterol: phospholipid ratios, transition temperatures are altogether indistinguishable

VII. Summary

Lipids have the common property of being relatively insoluble in water (hydrophobic) but soluble in nonpolar solvents. Amphipathic lipids also contain one or more polar groups, making them suitable as constituents of membranes at lipid:water interfaces. The lipids of major physiologic significance are fatty acids and their esters, together with cholesterol and other steroids.

Special Thanks to our References:

Lehninger PRINCIPLES OF BIOCHEMISTRY, 4e Harper’s ILLUSTRATED BIOCHEMISTRY, 27e Campbell’s BIOCHEMISTRY Prof. Leaño’s lecture – transcribed by Bryan Mesina, Jean

Mendoza, Mark Mauricio and Marvin Masalunga Doc Nic’s Biochemistry Module

Greetings from the Transcribers:

Alphius: Hi Class 2014! :-) I am Ralph Julius Mendoza. I hope that the reader of this trans will find this historical piece useful and inspiring. Good luck to everybody and may we get to know each other more…

Should you have any question regarding our trans, I’d be glad to be of service. Let’s all love biochem :-)

Para iba naman ang greeting… comics time! ~Mau~AFTG! (All For The Girls?! hahaha)

Oy Bryan ang haba ng greeting mo! Andaming girls sa greeting mo ha. Sino ba talaga sa kanila?! Hahahaha.

Bryan: Howdy 2014!! Hope y’all enjoy our trans on nothin’ but fats!! Get it? Fats?? *insert silence here* I’d like tah give an effer-y shoutout tah mah iMed peepz!! I miss y’all so effin much!! We should hang more often…seriously. Hello tah mah fellow iMed cheerdancers! Sana hindi niyo pa nakakalimutan yung mga steps!! We’d perform our routine again someday!! Haha! Hi tah thuh 8 Ducklings!! Hi too tah mah fellow Alphamales!! Sa next birthday ng isa sa’tin ah! Hi tah Block 13 and 14 at sa mga nagfee-feeling na Block 14!! :P Sa bio25 at bio30 groupmates ko, reunion tayo! Siyempre, I wouldn’t fo’get, hi tah mah 122 new friends!! I’ve talked or have at least greeted 120 of ye..2 nalang!! And swear, I’ve memorized all yer faces and names!! :D So tah those 2 people, watch out! One of these days..I’d greet ye!! O eto, personal greetings: Denden, di ko pa kayang baguhin language ko! AA, may love interest ka na pala ah! Roland, I still hafta skin ye alive!! Pero not before yer boards sa Saturday..good luck!! Karla, sana maintindihan mo ‘to..although I doubt it..haha! Mommy Carla Boz..i miss yer hugs! Lee-Ann, class picture!! :P Jegar and his narcoleptic buddies, we support ye!! Sa Saturday futsal club, laro ulit tayo! Shayne, “hun”, I miss ye! RR, gah! Lau, Julie (aka Bo-bo) and Dana, secret lang yun ah and thanx sa net!! Sa mga katokayo ko sa class, hey! Jesha, ligawan mo na kasi si Dr. Papa P! Jay, may bayad si…ehem…haha! Dogfish!! Maetrix, di ko na aalamin..kasi sasabihin mo din naman eventually sa’kin!! Alex, ano nang nickname ni blood brain barrier?? Hahaha! Jhing, September 5 ah! Bea, ye really look like Toni…and Reese too…hahaha! Sa mga fellow LOs ko na nagpapakahirap, saya no? Marvie!! Makakalimutan ba naman kita? Kahit na 3 seconds lang ang memory mo fo’ me..haha! I miss ye!! Lastly, a




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shoutout tah mah bestfriend Pito! Oi baller ko!! 4-words and Peace&Bounce man! B-) Waw..haba na pala nitong greeting ko..haha! 1:26am na sa clock ko…EFFER!!!

P.S.: Mau, ano? I-highlight ko? Hahaha! :P

Jean: CONG-GRA-TU-LATIONS! NOW NA!Tulong tayo lahat sa Lady Med! Sept 4 na! Yay. Yay. Yay. Seryoso ako.

September 4!!!!!!!!LADY MED!!!!!

VIII. ATTACHMENT

Fig. 1. Lipids-in-focus. Note the “Common Denominator”: Fatty Acid

Fig. 1. Lipids-in-focus. Note the “Common Denominator”: Fatty Acid

Table. 1. Some Naturally Occurring Fatty Acids: Structure, Properties, and Nomenclature




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*All acids are shown in their nonionized form. At pH 7, all free fatty acids have an ionized carboxylate. Note that numbering of carbon atoms begins at the carboxyl carbon.†The prefix n- indicates the “normal” unbranched structure. For instance, dodecanoic” simply indicates 12 carbon atoms, which could be arranged in a variety of branched forms; “n-dodecanoic” specifies the linear, unbranched form. For unsaturated fatty acids, the configuration of each double bond is indicated; in biological fatty acids the configuration is almost always cis.




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structure and function of lipids

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