Download Lipids

Types of lipids
Chemistry 256
Lipids
• Basically, any biologically interesting
nonpolar molecule
• Thus they are primarily hydrocarbons,
with some (few) functional groups
• Generally built from small molecules
such as acetyl-CoA or isoprene (below)
Fatty acids – generally, even-numbered
carbon chains
• x:y notation indicates x
carbons with y
unsaturations
• z notation indicates double
bond at the z-carbon
• -n notation indicates
unsaturation at the nth
carbon from the methyl end
• Double-bond orientations
always cis (puts 60° kink
in chain).
Fatty acid properties
• More unsaturation = lower melting point
(fewer London interactions to overcome
due to the kinks in the chain)
• Longer chain = higher melting point
(more London interactions to overcome)
Triacylglycerols = triglycerides
main components of fats (solid) and oils (liquids)
To make a triacylglycerol
• Condense three
fatty acids (they do
not need to be the
same fatty acid)
onto the alcohol
groups of glycerol.
• Biodiesel, for
instance, has this
structure.
• Energy storage
Glycerophospholipids = phosphoglycerides,
key membrane component
X = H (phosphatidic
acid), CH3CH2NH3+
(phosphatidylethanolamine),
CH3CH2N(CH3)3+
(phosphatidylcholine)
Polarity in glycerophospholipids
• Note the “head”
group (i.e., the
phospho-X group) is
charged, though
overall neutral. This
lends polarity to an
otherwise fairly nonpolar molecule
Phospholipases hydrolyze glycerophospholipids, release
fatty acids
Problem: How does a nonpolar substrate get anywhere
near a (polar) enzyme for a reaction to take place?
One strategy that is
found with
phospholipase A2 is
for the phosphate
group head to
interact deep in the
active site, and the
hydrophobic tail kept
in place by
hydrophobic
interactions with side
chain aromatic
groups. (Barden, Darke,
Deems and Dennis
“Interaction of phospholipase
A2 from cobra venom with
Cibacron Blue F3GA” (1980)
Biochemistry 19)
Plasmalogens have an ether
linkage. Function of these
molecules is not wellunderstood, though there is
some evidence that they react
with free radicals that prevents
myelinization of nerves (for
instance, see Gorgas, Teigler,
Komljenovic and Just, “The
ether lipid-deficient mouse:
tracking down plasmalogen
functions” (2006), Biochimica
et Biophysica Acta 1763).
Sphingolipids are amino alcohols – note
the amide in R2 and vinyl group in R3
• Named in the 1920s, when
Egyptology was all the rage
(“Sphinx” = mysterious) and
these compounds were
discovered and their function not
known at the time
• Now known to have many
functions, including nerve cell
sheaths (electrical insulation),
cell-cell recognition
• The sphingomyelin shown is a
type of sphingolipid called a
ceramide.
Sphingolipids can be quite complex - a
ganglioside has an oligosaccharide attached
Steroids – structure unlike the other lipids;
basically, four fused rings, roughly planar
Steroid carbon numbering system
• The fused ring system
is lettered A, B, C, D as
shown
• Numbering of carbons
starts on ring A; C-18 is
always a methyl off C13, C-19 is always a
methyl off C-10, and C20 on up is always off
of C-17
• Sterol alcohol is always
on C-3
Steroid synthetic history
• Adolf Butenandt and
G. Hamish (1935)
“A method for
preparing
testosterone from
cholesterol” was the
first synthesis of a
steroid hormone
Steroid functions – mostly a
eukaryote thing
• Cholesterol changes fluidity of a
membrane
• Glucocorticoids are stress hormones
regulating metabolism
• Mineral corticoids regulate excretion
by kidneys
• Androgens and estrogens regulate
sexual development and function
Isoprenoids = terpenoids, contain
isoprene units
• Functions as diverse as pigments (betacarotene), vitamins (retinol = vitamin A),
pheromones
In fact, when organisms decompose, isoprene and
isoprenoid units are some of the most abundant compounds
generated (Wallach, 1887). Fossil fuels (petroleum and coal)
contain a great number of isoprenoids.
Eicosanoids = icosanoids, which are
mostly prostaglandins
• Word derived from “eikos” = twenty; these compounds
are derived from twenty-carbon fatty acids
• “Local” hormones, work at or near site they were made
and then are rapidly degraded
• Key to inflammation and pain response
The first prostaglandins
were discovered by Ulf
von Euler (Karolinska
Institute, Stockholm) in
1935; he won the Nobel
Prize in Medicine in
1970. Prostaglandins
work at very low
concentrations.
fever
pain
inflammation