Intro to Lipids and Membranes

Lipids and biological molecules are grouped, not by their chemical structure or function, but by their……
poor solubility in water
What are the six major classes of lipids
fatty acids
triacylglycerols
glycerophospholipids
sphingolipids
waxes
isoprene-based lipids
What are the 3 major types of fuel our body uses?
carbohydrates
fatty acids
amino acids
What is the general structure of fatty acids? What are the common names for FAs with 12, 14, 16, 18, and 20 carbons (saturated).
-fatty acids are composed of a hydrocarbon skeleton with a carboxyl group.
-12 carbons – Lauric acid
-14 carbons – Myristic acid
-16 carbons – Palmitic acid
-18 carbons – Stearic acid
-20 carbons – Arachidic acid

*note that most natural fatty acids have an even number of carbons

What are the two major classes of fatty acids?
saturated – no double bonds
unsaturated – have double bonds
A typical fatty acid will have a very long hydrocarbon tail, and a short hydrophilic carboxyl group. The hydrophobic tail is poorly soluble in water. Fatty acids are more soluble in organic solvents like benzene
The single bonds that form the skeleton rotate around each other, making the structure very flexible. However, the most stable conformation is the fully extended one.
– In this fully extended conformation, many fatty acids can pack against each other,
Unsaturated fatty acids, primarily linoeic and linolenic, are essential fatty acids because we do not have enzymes that introduce certain double bonds. We need them to synthesize prostaglandins, throboxanes, etc.
Do unsaturated fatty acids typically have cis or trans double bonds? Why is this important?
Cis – meaning the molecule will bend

This is important because the kinks affect their ability to interact with each other and saturated fatty acids.

Most of the time unsaturated fatty acids are liquid because they cannot pack and interact effectively with one another. This is very important because a percentage of unsaturated fatty acids that are present in our membranes largely determine the physical properties of our membranes. You will always find unsaturated fatty acids in our membrane, allowing it to stay fluid.

This is less important for warm blooded animals whose body temp is such that membranes are naturally fluid. In plants, however, which are exposed to ambient temp, it can be a real problem. In plants and other cold blooded animals, the proportion of unsaturated fatty acids are greater than in warm-blooded animals.

How do u name an unsaturated fatty acid?
take the total number of carbons followed by a colon and the number of double bonds followed by a “delta” and the carbon numbers of the double bonds.

see table on 8 slide in notes

6 common unsaturated fatty acids:
palmitoleic acid (16:1)
oleic acid (18:1)
linoleic acid (18:2)
alpha-linolenic acid (18:3)
gama-linolenic acid (18:3)
arachidonic acid (20:4)
You typically do not find fatty acids free in the body. If you look at the concentration of free fatty acids in a well-fed human, the concentration is really low.
The concentration you find in the blood may still sound high when you look at the solubility of fatty acids, but this is because specialized proteins, like serum albumin, are made to specifically bind fatty acids and transport them to other tissues.
What is one circumstance where the circulation of free fatty acids becomes great?
starvation

fatty acids are the primary storage form of energy in the body. Most of the time, the major source of carbons for oxidation are carbohydrates, but when we are starving, our reserves of carbohydrates are limited, so metabolism switches to the oxidation of fatty acids.

Different foods have different proportions of saturated and unsaturated fatty acids.
– butter (high saturated fat)
– plant oils (high unsaturated fat)

Diets rich in unsaturated fats are generally healthier than diets rich in animal fats.

What are the three major functions of fatty acids?
metabolic fuels
structural components
precursors for a number of important biological molecules
What are eicosanoids?
-important biological molecule that comes from fatty acids
-derivatives of arachidonic acid
-fall into three groups (prostaglandins, thromboxanes, and leukotriens)
-chemically very similar to arachidonic acid.
-Eicosanoids are known to be involved in reproductive function, in the formation of blood clots and the regulation of blood pressure, in gastric acid secretion, the wake-sleep cycle, cause inflammation and pain, induce contraction of the muscle lining the airways to the lung
What is the major differences between prostaglandins, thromboxanes, and leukotrienes?
prostaglandins
– pentene ring
thromboxanes
– six-membered ring
leukotrienes
– have oxy groups incorporated into the skeleton
What do NSAIDs like Ibuprofen and Vioxx do?
inhibit synthesis of prostaglandins and thromboxanes
What are triacylglycerols (triglycerides)?
-the most abundant form of fatty acids because it is the storage form of the molecule
-when you ingest fatty acids, they are esterified with glycerol, transported through the bloodstream and deposited in our adipose tissue in the form of triacylglycerols
-when there is a need, fatty acids will be mobilized from the adipose tissues and delivered to other tissues as bound to serum albumin.
Why does our body use triglycerides as a form of energy storage?
-it is the most reduce form of carbon you will find
-most of the carbons in carbohydrates have hydroxyl groups attached, meaning that it is partially oxidized already
-you can release more energy by oxidizing triglycerides than you can by oxidizing carbohydrates of fatty acids.
-another great advantage is that triglycerides are also not soluble in water. in adipose tissue they form oily droplets inside the cell. as a result, you dont need to bring any additional water into the cell to keep them soluble, unlike with glycogen, which is highly hydrophilic, where you have to bring water in. this requires bringing in more ions which you have to expend energy to pump out later on
-triglycerides also pack efficiently into cells
What is the structure of triglycerides?
they are made of a glycerol with 3 hydroxy groups which is esterfied with 3 fatty acids. there are almost no hydrophilic groups to the molecule.
What are the two forms of triacylglycerols?
simple triacyglycerols – have three of the same fatty acid attached

mixed triacylglycerols – 3 different fatty acids attached to glycerol

-most will be mixed

-there are about 280kcals of glycogen stored in the liver
-fat stores much more energy
-every time we have any extra energy, it will eventually be converted into triglycerides and stored in adipose tissue.
In addition to being a source of energy, what are three other advantages to using triglycerides?
-help with insulation
-are a source of metabolic water
*the final products of oxidation are CO2 and water – for humans this may not be important, but for hibernating animals, this may be their only source of water
-are a source of energy that does not produce nitrogen
*when you use amino acids as sources of carbons for oxidation, you produce ammonia, which is toxic. we use the urea cycle to get rid of the excessive nitrogen which is expensive in terms of metabolism. a lot of the energy released in the metabolism of amino acids will be used in the liver to get rid of the ammonia that was released.
What molecules make up membrane lipids?
glycerophospholipids
-are amphipathic
-have a hydrophobic part made up of fatty acid tails and a highly polar part made of a phosphate head group.
-the head group can readily interact with water and the tail groups can readily interact with each other
-this is a critical arrangement for building biological membranes
what are the two large groups that lipids can be divided into?
phospholipids and glycolipids
Phospholipids
-have a phosphate group as an integral part and can be divided into two groups
-glycerophospholipids:
*built on a skeleton of glycerol; C1 and C2 hydroxyls are acylated by fatty acids. The fatty acids at C2 are typically unsaturated or polyunsaturated (ex: release of arachidonic acid for synthesis of prostaglandins will come from this position)
*in addition, the C3 hydroxyl is acylated by phosphate, which, in turn, has an alcohol attached to it.
*the building block of glycerophospholipids is phosphatidic acid. it is glycerol acylated to fatty acids at the oxygens at C1 and C2 and phosphoric acid attached to the oxygen at C3.
*all phospholipids have an alcohol attached to the phosphoric acid (ex: choline, ethanolamine, serine)

-sphingolipids:
*not build on a skeleton of glycerol but on a skeleton of amino alcohol sphingosine. sphingosine is acylated to a fatty acid and a phosphate group with an alcohol attached.

Glycolipids
in contrast to phospholipids, do not have phosphate group. they are built on a backbone of sphingosine, with a fatty acid attached to the amino group and a polysaccharide residue attached to the hydroxyl group.
Phospholipases.
enzymes that are involved in breaking down different phospholipids
-they are distinguished by their ability to break different parts of the phospholipid molecule.
-phospholipase A2 breaks down at C2.
-phospholipase C breaks the bond between glycerol and the phosphate.
-some toxins and venoms are also phospholipases. cobra venom is a phospholipase that hydrolyzes fatty acids at C2, making lysolecithin, a detergent that breaks down the membrane
Ether Glycerophospholipids
-instead of a fatty acid at C1, there is an alcohol attached with an ether bond.
-they are ofund mainly in the heart muscle. The ether bond supposdely make sthe molecule mor estable but there is not much evidence of that.
-One ether glycerophospholipid worth mentioning is platelet activating factor (PAF).
*signaling molecule
*instead of a long fatty acid at C2, it has a short acyl group, making it soluble. It is released from leukocytes and mediates processes like inflammation, allergic response, etc.
Sphingolipids
-built on a backbone of sphingosine.
-a lot of them are found in the brain and cardiac muscle; they are typically a structure component but many are involved in signaling
-sphingosine is an amino alcohol. the amino group is acylated by a fatty acid, similar to a peptide bond and forms a building block called ceramide.
Depending what is attached to the hydroxyl group of sphingosine, you will have different groups of sphingolipids.

What are sphingomyelins, glycosphingolipids, and gangliosides?

sphingomyelins – have a phosphate head group attached to the hydroxyl

glycosphingolipids – have a sugar attached to the hydroxyl

gangliosides – have three or more sugars, one of which is sialic acid
*they are important as structural components of neurons and are involved in signaling neurons. There are a number of diseases associated with the degradation and synthesis of gangliosides.

Waxes
-esters of long chain alcohols with long chain fatty acids
-link forms between hydroxyl group of alcohol and carboxyl hydroxy group of fatty acid
-highly insoluble and present on animal skin/fur, plant leaves, bird feathers
Terpenes
-are a very diverse group of ocmpounds derived from isoprene.
-isoprene is a 5-carbon compound that has two double bonds and can readily polymerize from head to tail or tail to tail
Monoterpenes, Diterpenes, Triterpenes, Tetraterpenes
-Monoterpenes
*have 10 carbons, mostly found in plants
*typically recognized for their flavors or odors (limonene in lemons; menthol)

-Diterpenes
*found in animals
*ex: Retinal – the essential light-absorbing pigment in rhodopsin, the photoreceptor protein of the eye

-Triterpenes
*them and their intermediates will be discussed in the biosynthesis of cholesterol

-Tetraterpenes
*beta-carotene, lycopene

-besides the ones shown, many terpenes are important vitamins. Vitamin K is important in blood clotting, vitamin E is an antioxidant that prevents membranes and triglycerides from oxidation by oxygen, and coenzyme Q is important in metabolism in mitochondria.

Steroids
-all steroids are derived from cholesterol.
-the basic structural components are the four fused rings (3-six member rings, 1-5 member ring) with different tails attached to different parts.
-the primary structure of cholesterol is a structural complement of membrane, which largely dictates its fluidity. its sort of like a brick
-it is also a precursor for an enormous amount of signaling molecules
-serve many functions including salt balance, metabolic function, and sexual function