Lipids

1
Lipids

• Lipids are highly reduced (i.e.
  oxidation-reduction) carbon-rich substances that
  are insoluble in water.
• The functions of lipids in the cell are diverse.
• Storage Lipids
• Triacylglycerols
• Membrane Lipids
• Phospholipids
• Glycolipids
• Reading Lehninger Chapter 11 pp. 363-388

2
Fatty Acids

• Fatty acids are carboxylic acids with hydrocarbon
  chains ranging from 4 to 36 carbons in length.
• Some fatty acids are saturated, meaning that
  they contain no double bonds between two
  consecutive carbon atoms of the alkyl chain.
• Some fatty acids are monounsaturated, meaning
  that they contain one double bond between two
  consecutive carbon atoms of the alkyl chain.
• Some fatty acids are polyunsaturated, meaning
  that they contain more than one double bond in
  the alkyl chain.

3
Fatty Acid Nomenclature

• In practice, common names are used more often
  than systematic names. You should be familiar
  with the systematic names for the C12-C20 fatty
  acids.
• When naming fatty acids, all carbons count the
  carboxyl group as well as the alkyl chain.
• Notice that some of these fatty acids have double
  bonds. You should be familiar with the
  convention for naming or specifying the position
  of the double bond.
• Counting starts from the carboxyl carbon, and the
  numbering begins at the first carbon of the
  double bond.
• Notice the convention for naming compounds with
  multiple double bonds.
• In nature, almost all fatty acids have an even
  number of carbons. This is due to the fact that
  fatty acids are synthesized stepwise from acetyl
  building blocks.

4
Physical Properties of Fatty Acids (Length)

• The physical properties of fatty acids are
  largely determined by the length and degree of
  unsaturation of the hydrocarbon chain.
• Fatty acid chain length
• The longer the fatty acid chain length, the
  poorer the solubility in water.
• Because the carboxylic acid of the fatty acid is
  polar, it accounts for the moderate solubility of
  short-chain (less than 10 carbons) fatty acids in
  water.
• The longer the fatty acid chain (assuming the
  degree of unsaturation remains the same), the
  higher the melting point.
• Degree of unsaturation
• mkln

5
Physical Properties of Fatty Acids (Degree of
Unsaturation)

• The degree of unsaturation also is very important
  in determining the physical properties of fatty
  acids.
• The fewer the double bonds in a fatty acid
  (assuming that the length of the fatty acid
  remains the same), the lower the solubility of
  the fatty acid in water.
• The fewer the double bonds in a fatty acid, the
  higher the melting point of the fatty acid. This
  assumes that the length of the fatty acid remains
  the same, and that the double bonds present are
  all in the cis configuration.
• The effect of the double bond on the physical
  properties of lipids is due to the conformation
  of the lipid that is caused by the double bond.
• In saturated lipids (especially those of the same
  length), the most stable arrangement is very
  close packing of the side chains of the lipids,
  which is due to van der Waals interactions. The
  packing is such that the lipids assume an almost
  crystalline array.
• Because of the kink that results from cis double
  bonds, tight packing of fatty acid chains cannot
  take place.
• Since the interactions between the these arrays
  are less extensive, it takes less energy to
  disrupt them, resulting in a lower melting point.

6
Double Bonds

• In nature, double bonds are most often found in
  the cis conformation. There are cases where
  trans double bonds are known, however, these are
  seldom found in membranes.
• A trans double bond fixes a given fatty acid in
  an extended conformation, similarly to how a cis
  double bond fixes a given fatty acid in a kinked
  conformation.
• Trans fatty acids can pack similarly to saturated
  fatty acids, and thus they have markedly higher
  melting points.
• Trans fatty acids are often produced from healthy
  unsaturated fatty acids in a process called
  hydrogenation. The goal of hydrogenation is to
  reduce the double bond by adding hydrogen gas
  across it. This results in the raising of the
  melting point of oils like corn oil, safflower
  oil, or sunflower oil, so that they are solid
  around room temperature. This is how margarine
  is made.
• Trans fatty acids have recently gained notoriety
  as being worse with respect to heart disease than
  even saturated fatty acids. They are found in a
  variety of cookies, chips, and commercial baked
  goods. They can also be produced when oil is
  used for frying foods.
• Double bonds can also be oxidized and cleaved to
  aldehydes and carboxylic acids when they sit in
  air for too long. This is what results in
  rancidity of oils.

7
Unusual Fatty Acids

• There are many unusual fatty acids that occur in
  the membranes of various bacteria. In one case a
  methyl group is donated to an unsaturated fatty
  acid to generate a branched-chain fatty acid, as
  in tuberculostearic acid.
• A methylene group can also be added across the
  double bond to give a cycylopropane ring as in
  lactobacillic acid. Bacteria that cause leprosy
  and tuberculosis have many of these cyclopropane
  rings as constitutents of their cell walls. They
  are also correlated with their virulence.
• Other modifications include hydroxyl groups,
  ketone groups, epoxides, and methoxy groups.

8
Triacylglycerols

• Fatty acids are rarely found floating free in
  solution. They are almost always connected to
  something.
• In the blood, they are complexed noncovalently to
  the protein serum albumin.
• In blood plasma fatty acids exist predominantly
  in an esterified form, or in an amide linkage.
• A large proportion of fatty acids in biological
  systems exist as triacylglycerols (an esterfied
  form). This is the primary storage form of body
  fat.
• Since the carboxylates are esterified, and no
  longer can bear a negative charge,
  triacylglycerols are very nonpolar, and are
  therefore insoluble in water.
• The acyl groups can be cleaved from the glycerol
  backbone very efficiently by heating in acid or
  base. For example soap was traditionally made
  from taking animal fat and treating it with
  potassium hydroxide (which was garnered from wood
  ashes). You would get the potassium salt of the
  fatty acid.
• In the cell, specialized enzymes, called lipases,
  catalyze the hydrolysis of the ester of
  triacylglycerols in order that the fatty acid can
  be used for fuel or other purposes.
• The advantage to using triacylglycerols as
  storage fuel rather than polysaccharides, is that
  (1) more energy is present per carbon atom
  because fatty acids are typically more reduced
  than are carbohydrates (2) because fatty acids
  are nonpolar, they are not hydrated by water. In
  other words, an organism doesnt have to carry
  the water that is necessary to hydrate the fatty
  acid.

9
Glycerophospholipids

• Glycerophospholipids are the primary
  constitutents of cell membranes.
• Note that glycerophospholipids differ from
  triacylglycerols in that only two of the hydroxyl
  groups of glycerol are esterified to fatty acids.
  The third hydroxyl group contains a phosphate
  group that is connected to a given head group
  via a phosphodiester bond.
• Note the common head groups that are found, as
  well as their structures and names. You should
  be able to recognize the structures of the given
  head groups and match them to their names.
• The head group charges and / or polarity
  contribute greatly to the surface properties of
  membranes.
• The fatty acid distribution as well as the head
  group varies from species to species, and in
  higher organisms from tissue to tissue.

10
Ether-Linked Fatty Acids

• Some organisms as well as certain animal tissues
  contain signficant amounts of ether-linked fatty
  acids.
• Ether-linked fatty acids are typically found on
  only one of the fatty acid chains of a
  glycerophospholipid.
• The significance of ether-linked lipids in
  unicellular organisms is not rigorously known.
  We know that ethers are more resistant to
  cleavage than esters, and therefore they would be
  resistant to the abundant lipases that are found
  in cells.
• Platelet activating factor is an important
  compound containing an ether-linked alkyl chain.
  It acts as a molecular signal. In one case it
  stimulates platelet aggregation, and also is
  important in inflammation.

11
Waxes

• Waxes are esters of long-chain saturated and
  unsaturated fatty acids with long-chain alcohols.
• Waxes typically have fairly high melting points,
  espeically when compared to triacylglycerols.
• Certain skin glands of vertebrates secrete waxes
  to protect hair and skin and keep it pliable,
  lubricated, and waterproof.

12
Sphingolipids

• Sphingolipids make up the second largest class of
  phospholipids.
• The most distinct difference between
  sphingolipids and glycerophospholipids is that
  the backbone of sphingolipids is NOT glycerol.
• Sphingolipids contain sphingosine (shown in red),
  which is a long-chain amino alcohol. A fatty
  acid is joined to sphingosine via an amide
  linkage rather than an ester linkage as seen in
  glycerol. When the fatty acid is present on
  sphingosine, the general name of the lipid is
  ceramide.
• Note the various head groups that are found on
  sphingolipids. Several of the head groups
  contain sugars. These glycosphingolipids are
  found largely in the outer face of plasma
  membranes.

13
Importance of Sphingolipids

• Apparently (from reading your book), when Johann
  Thudichum discovered sphingolipids at the turn of
  the 20th century, he had no idea why they were
  present. Thats why the name is derived from the
  Sphinx.
• We now know that many are involved as cell
  surface recognition sites.
• One well-known function of sphingolipids is that
  they function as cell surface antigens, defining
  the various blood types.
• The human blood groups are determined in part by
  the type of sugars located on the head groups.
  In the ABO system, the determinating gene is
  located on chromosome 9, and encodes one of
  several glycosyltransferases.
• If the gene encodes a protein that transfers an
  N-acetylgalactosamine group, this corresponds to
  the A antigen.
• If the gene encodes a protein that transfers a
  galactose group, this corresponds to the B
  antigen.
• If the gene does not encode an active
  glycosyltransferase, this corresponds to the O
  antigen.

14
Sterols

• Sterols are structural lipids that are present in
  the membranes of most eukaryotic cells.
• The general sterol has four fused rings, three of
  which are six-membered, and one of which is
  five-membered.
• The main body of sterols is planar.
• Cholesterol is shown at the left.
• Sterols can modulate the fluidity of membranes.
• Many hormones are derivatives of sterols.

15
Steroid Hormones

• Steroids are oxidized derivatives of sterols.
  Can you determine where oxidation occurs from the
  precursor sterol? Can you describe how many
  electrons are involved in the oxidation?
• Steroids have the main body of sterols, but do
  not have the alkyl chain, like in cholesterol.
  This makes them more polar than cholesterol.
• Steroid hormones move through the blood stream
  primarily attached covalently or noncovalently to
  protein carriers.
• Many of the steroid hormones are male and female
  sex hormones. Can you recognize some of the
  names?