PM150 Lecture 10 - Simple Lipids WATCH LECTURE RECORDING

Lipids

  • Lipids are a large and varied group of compounds with a number of biological functions:

    • Major structural elements of membranes

    • Fuel molecules and can act as energy stores (e.g. TAGs)

    • Some lipids act as hormones, intracellular messengers and vitamins

    • Some lipids have specialist functions e.g. protective and insulating barriers as in leaf cuticle or the bile salts that act as biological detergents in digestion.

  • Lipids are “simple” or “complex”

    • Simple: Waxes and neutral lipids (storage fats)

    • Complex: Phospholipids and glycolipids that have a structural role.

Simple lipids

  • Are esters- which contain the -O- alkyl group

  • Their hydrolysis yields an alcohol and fatty acids. The fatty acids are typically long chain (more than fourteen carbon atoms).

  • e.g. waxes are esters formed from a long chain fatty acid and a long chain alcohol; a typical example of a wax is myricyl palmitate, which is the ester formed from myricyl alcohol and palmitic acid and is the major component of beeswax.

Structure of Fatty acids

  • The general formula of fatty acids:

  • Saturated fatty acids: contain no carbon-carbon double bonds. The most abundant examples are palmitic and stearic acids (where n = 16 and 18 respectively).

  • Fatty acids have “common” and “systematic” names

    • Systematic name is derived from the name of the parent hydrocarbon with substitution of the suffix (-oic in place of -e)

      • e.g. for stearic acid (18 carbons), the parent hydrocarbon is octadecane and the systematic name is octadecanoic acid.

  • Unsaturated fatty acids: have carbon-carbon double bonds in the fatty acid chain. Monounsaturated fatty acids have a single double bond whereas polyunsaturated fatty acids have more than one.

  • Systematic nomenclature of unsaturated fatty acids: the suffix -e of the parent hydrocarbon is replaced with:

    • -enoic for one double bond

    • -dienoic for two

    • -trienoic for three

    • We can have octadecenoic, octadienoic and octadecatrienoic acids.

  • Alternative nomenclature:

    • Omega

  • Essential fatty acids - essential because body cannot make it. dependent on diet

  • w-3 fatty acids health implications: regulates blood cholesterol, reduces blood pressure, maintains health brain health, important in foetal development

  • w-6 fatty acids as precursor molecules: arachidonic acid and linoleic acid are important molecules that can be used to synthesise endocannabinoids and eicosanoids

Fatty acids have many roles associated with the membrane

  • Signalling molecules

    • Disease pathology, clinical outcomes

General features of naturally occuring fatty acids

  • Fatty acids found in nature tend to have an even number of carbon atoms

    • However odd chain fatty acids are present in small amounts in nature, generally in plants and microorganisms.

      • C11-C33 are present in small amounts (up to 3%) in the animal kingdom, usually present in ruminant fat and milk.

      • The most common odd chain fatty acids are C15 and C17.

  • Fatty acids from animals are generally unbranched (straight chain)

  • The configuration of the double bonds in most fatty acids is cis, not trans

  • The double bonds in polyunsaturated fatty acids are separated by at least one methylene group (never conjugated)

Categorisation of fatty acids

  • Fatty acids can be categorised according to their length

Protein modification by fatty acids

  • Post-translational modification of proteins with a fatty acid

  • Alter protein function e.g. alter their localization within a cell, facilitate attachment to a cell membrane or specific receptor.

  • New area of research

  • Fatty acids reported to bind to proteins

    • C2:0, C4:0, C6:0, C8:0, C10:0, C12:0, C14:0, C16:0, C16:1, C18:0, C20:4 (most reported to bind to proteins)

The effect of modification by fatty acids

  • Ghrelin - a stomach hormone that travels to the brain to cause the sensation of hunger

    • Only active when bound to a fatty acid

Summary - Learning outcomes for simple fatty acids

  • Fatty acids can be saturated or unsaturated (MUFAs or PUFAs)

  • Fatty acids can contain various number of carbon atoms and can be classified accordingly

  • Can be classified according to the location of the double bond (e.g. w-3 and w-6 fatty acids

  • Involved in membrane structure and precursors for many important signalling molecules

  • The degree of saturated will ultimately affect the physical properties of the fatty acid

  • Can be attached to proteins to alter signalling properties

Complex lipids part 1

Fatty acids and glycerol

  • Only a very small percentage of fatty acid residues present in living systems exist as free fatty acids, they are normally found esterified to a glycerol moiety.

  • Glycerol is a simple polyol that forms a backbone for many complex lipids.

Monoacylglycerides (MAGs)

Diacylglycerols

  • Are two fatty acid residues esterified to glycerol.

  • Exist either as 1, 2-diacylglycerols or 1,3-diacylgylcerols

  • Acyl migration can occur, so these forms can be in equilibrium

  • Common diacylglycerols contain C14:0, C16:0, C16:1, C18:0, C18:1, C18:2

    or C20:0

  • Are found in both animal and plant cells

  • Both monoacylglycerides and diacylglycerides are widely used as emulsifies in food products

  • Are formed either as a byproduct of triacylglyceride biosynthesis or its metabolism

  • Acts as secondary lipid mediators during cellular signaling

  • Diacylglycerides activates protein kinase C (PKC) and induces the release of intracellular CA2+

  • Fatty acid composition of some Diacylglycerols reported to be involved with cellular signaling - C18:0, C18:1, C18:2, C20:4

    • These processes are important for many aspects of cell life, including the ability of a cell to respond to external growth factors - cellular growth, differentiation and movement e.g. important during healing

Triacylglycerols (Triglycerides)

  • These are three fatty acid residues esterified to glycerol. Mainly found in storage fats.

  • The molecule is drawn with the secondary fatty acid to the left of the central carbon with the carbons numbered from top to bottom.

  • Triacylglycerols are primarily found in adipocytes

    • Found in both the liver and the intestine but chiefly located in adipose tissue.

    • The specialised cell in the tissue is the adipocyte.

    • The cytoplasm of these adipocytes is full of lipid vacuoles that are almost exclusively composed of triaglycerols.

  • Triacylglycerols are effective storage molecules.

    • When metabolised fatty acids can contain more energy than carbohydrates.

    • Metabolism of 1 x glucose (C6H12O6) (via Glycolysis and TCA cycles and Oxidative phosphorylation) leads to the generation of about 30 molecules of ATP see Table 18.4: ATP yield from complete oxidation of glucose, page 518 Berg, Stryer

    • Metabolism of 1 x Palmitate (16:0) (C16H32O2) via fatty acid oxidation (Beta-oxidation)leads to the generation of 106 molecules of ATP

  • Homotriglycerides: all three fatty acids are identical, those that aren’t found naturally can be synthesised