Lipids: structure and functionBiochem I, lecture 3

Thurs, Sept 14, 2006

Chps 12.1-12.2 (& 26.4.8 of 5th ed.)

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

Macromolecule 1: LipidsRecall that we identified the four biomacromolecule classes

in the first lecture… Lipids Nucleic acids Carbohydrates Proteins

All of these molecules are organic: they all have a ________ backbone

LIPIDS:What are they?• Hard to define! • Of the 4 macromolecule groups, the most loosely classified• Nomenclature sometimes confusing and overlapping

– Based on “nonscientific” properties• “Lipid" includes substances such as oils, fats and waxes

Check out www.cyberlipid.org

Lipid propertiesLipid molecules share key “lipid-like”

properties that include: • presence in all living organisms• insolublility or immiscibility with water but

soluble in organic nonpolar solvents such as chloroform, ether, benzene and acetone, due to fat’s non-polar nature

• formed of long-chain hydrocarbon groups (carbon and hydrogen) but may also contain oxygen, phosphorus, nitrogen and sulfur

The typical definition of lipids

Lipid biological rolesLipids have four primary

functions in living cells (a/k/a “in vivo”):

• Fuel molecules• Highly concentrated energy

stores• Signal molecules• Components of membranes

– Phospholipids– Sphingolipids– Cholesterol

Fig 12.1

Major classes of lipids• fatty acids (FAs):

key constituents of all lipids– Typical structure is

CH3(CH2)nCOOH

– Even number of C: 14-24

– Typically ionized in vivo (hydroxyl group loses H)

– Fatty acids are often conjugated to other molecules to change their chemical properties

Fig. 12.2

C16

C18

Fatty acid examples

Major classes of lipidsThe other lipid classes generally contain fatty

acids conjugated to other molecules• Most familiar are glycerol-derived lipids

– Fatty acids conjugated to sugar alcohol with 3 carbons (typically connected by _______ bonds to 2 or 3 FAs)

– including the fats (saturated, mono- and poly-unsaturated) and oils (liquid fats) and the phospholipids

Fig 12.3Phospholipid basic structure

Fig 12.4: the simplest phospholipid

Glycerol core of a phospholipid

optional

For example…

Major classes of lipidsSphingosine-derived lipids (including the

ceramides, cerebrosides, gangliosides, and sphingomyelins)

• Sphingosine vs. glycerol backbone– 3-C core plus long hydrocarbon chain

Fig 12.6

• Functionally analagous to glycerolipids– Where are they found? Cell membranes, primarily

those in cells of the _ _ _– Animal sphingosine lipids can also contain sugars

= glycolipids– Sugar moiety always faces extracellular space

(why?)

p. 331

Major classes of lipids• Steroids and their derivatives

– e.g., cholesterol– basic skeleton consisting of four

interconnected carbon rings; different structure than long chain FAs

– These molecules bind to specific protein receptors, precipitating a signal transduction chain

• Terpenes and their derivatives

– Built from same 5-carbon precursor as cholesterol (isopentenyl pyrophosphate)

– Compounds also called isoprenoids

Fig 26.30, 5th ed.

p. 331

Major classes of lipids• certain aromatic compounds with a wide range

of functions also made of isoprenyl C5 subunits

• long-chain alcohols and waxes

Phytol side chain

Vitamin A

Long chain hydrocarbons, acids, alcohols, ketones, aldehydes, esters: COMPLEX

______?

Many lipid classes, many lipid functions

• Functions are obviously very diverse, fitting for such a large family of molecules– structural (in membranes) – signaling (steroids) – enzyme cofactors (vitamins)

• Diverse functions but an overall conservation of structure– Recall that all lipids have in common a hydrophobic fatty acid

chain, either linear or formed from isoprene subunits into ring structures

Hydrophobic chains and rings formed exclusively of C and H atoms

Fatty acids are the monomeric form of lipids• FAs (a/k/a “fats”) are the “building blocks” of functional

lipids• There are many different FAs and they can be

assembled into their final form in molecules in a number of ways– e.g., in phospholipids, a glycerol backbone is linked to two FA

molecules and one phosphate• FAs do not generally exist free in large quantity in vivo

but are complexed to other molecules depending on their function

• FA chain composed of an even number of C atoms• Hydrophobic nature arises from lack of dipoles formed

by C-H and C-C bonds present in chains:– neither C nor H is very electronegative (versus which 2

elements found commonly in biomolecules?)

Fatty acids may be saturated or unsaturated• The term “saturated” means that the hydrocarbon

tails are saturated with hydrogen atoms– no C=C bonds, just C-C and C-H bonds in the tail (plus

the carboxyl group)

• The number and placement of the double bonds affects the naming of the FA

• This also affects its chemical properties, and thus the properties of the lipid molecule into which it is incorporated (we’ll talk about this when we discuss membranes), as well as the effect of the lipid on your health (more on that later too)

Fatty acids are of various lengths and degrees of unsaturation

• FAs have three naming protocols• Consider a FA with 18 C and 1 C=C bond.

How can it be named? Let us count the ways…– Least descriptive is the numbering notation

• 18:1 = 18 Cs, one double bond

– the traditional name is more descriptive but the position of any unsaturated bonds is not immediately obvious

• oleic acid: named after the hydrocarbon root: oleane

Fig. 12.2

Systematic names give the most information

• the systematic name tells the number of C in the FA chain, the degree of unsaturation, C=C bond placement in the molecule and its stereochemistry– cis-Δ9-octadecenoic acid– Again named after parent hydrocarbon: octadecane

• Systematic suffixes vary according to unsaturation– 0 double bonds = octadecanoic acid– 1 “ “ = -----------enoic acid– 2 “ “ = -----------dienoic acid

&c.

Systematic names also inform about position• Numbering of C in FAs starts with carboxyl C• C2 and C3 often called α and ß• Methyl C at distal end of chain called ω-carbon

atom• Position of double bond(s) also indicated by Δ

– cis-Δ9 indicates a double bond in cis between C9 and C10– trans, trans- Δ9, Δ12 indicates 2 C=C bonds, both in trans

between C9-10 and C12-13– Know the difference between cis and trans

p. 328

Non-standard nomenclature can also inform C=C bond position

• Also common is counting from the methyl end of the chain for some FAs (to minimize number used)– ω-3 FAs

• Note that all FAs are ionized at physiological pH (~____) because of COOH group’s low pK of ____

• Can thus refer to FAs by carboxylate (COO-) form: palmitate, cis-Δ9-octadecenoate

p. 328

Systematic versus traditional names

• Systematic name is preferred nomenclature because of the standard terms used– It’s probably easier to recall that a C18 FA (without any double C=C

bonds) is called octadecanoic acid rather than stearic acid

• In health and popular literature (and on Nutrition Facts labels) this FA may also be described as monounsaturated

• Be aware that all these terms refer to the same molecule!

Name this:

Many FAs in animal tissues are saturated• Most common FAs in animals and

plants are C16 and C18• Usually have even number of C• Animal fats (triglycerides) _______

at room temp while most plant fats are __________

• This is due to differences in the degrees of unsaturation of FA chains

• Most animal fats are saturated, most plant fats have at least one C=C bond

• Chain length and degree of unsaturation affects FA characteristics

• Short chain length and unsaturation lower FA melting temperature– Introducing 1 cis DB lowers C18

melting point from 70° to 13°– This enhances the fluidity of

molecules that include these FAs

saturated

monounsaturated

diunsaturated

triunsaturated

cyberlipid.org

stearate

oleate

Table in textbook outlines major animal fatty acids

• Again proportionately more saturated FAs present than in plant derived FAs

• Common names are ancient; give clue of original source of many FAs

Lipid synthesis and degradation• (Chp 22)• Synthesizing complex molecules from simple precursors

(anabolism) and breaking them down via catabolism involves a series of oxidation and reduction (a/k/a r_____ ) reactions, respectively

• For synthesizing a functional lipid, there are 2 separate processes to consider– Make the hydrophobic acyl chain– Complex it (usually by esterification) to another molecule that

fulfills a specific function in vivo

• 2 major places where FAs play a role in metabolism is when they are incorporated into either– triacylglycerols (triglycerides) for energy storage, or– phospholipids for incorporation into membranes– Both of these molecules possess a glycerol backbone

FA synthesis and degradation are mirror image processes

• FA catabolism and anabolism are reciprocally regulated in response to hormone levels in animals and plants

• Processes are the reverse of each other

• Degradation converts storage fat (triacylglycerol) into small 2-carbon, activated acetyl units that can be processed by the TCA cycle in a process called o______ p__________

When we discuss the metabolism of a compound, we are referring to how it is taken up and used to help keep an organism homeostatic (and healthy!)

oxidation

reduction

p. 617

Let’s look first at FA degradation• To degrade FAs, the body must first get

them out of “storage”• Lipids are stored as triacylglycerols in

adipose tissue• Mammals are capable of storing large

amount of lipids in specialized cells called adipocytes

• A good Q: Why store lipids (why not carbohydrates?)

• It is because lipids can store more energy in a smaller volume

Lipids are high-energy compounds• Complete oxidation of a lipid into acetyl-CoA 2-carbon

units yields 9 kcal/g, versus 4 kcal/g for carbohydrates• PLUS, lipids are nonpolar and thus almost completely

anhydrous = lipids are reduced, meaning they possess a lot of ______ but not many _____ atoms

• 1 g storage carbohydrates (the polysaccharide g______ ) complexes with 2 g water

• Thus 1 g anhydrous fat stores (9 kcal/g / 4 kcal/g) x (3 g CHO / 1 g lipid) = 6 X as much energy as 1 g carbohydrate

Fig 22.1: adipocyte

p. 617

Lipids are an energy rich storage compound• The energy “richness” of triacylglycerols are the likely

reason they were chosen over storage carbohydrate (glycogen) as our main energy stores during evolution

• Typical 70-kg man has energy stored as– 1 x 105 kcal in triacylglycerols– 2.5 x 104 kcal in protein (muscle)– 600 kcal in glycogen– 40 kcal in glucose

• Triacylglycerols are ~11 kg of body mass (~16% body fat)• Would need 6x this mass to store the same energy as

glycogen!• Carbohydrate stores alone allow maintenance of

metabolism for ~24 h; stored lipids allow survival for weeks