Lipids

What are Lipids?

Lipids are molecules that contain hydrocarbons and make up the building blocks of the structure and function of living cells. Examples of lipids include fats, oils, waxes, certain vitamins, hormones and most of the non-protein membrane of cells.

What are lipids soluble in?

Lipids are not soluble in water. They are non-polar and are thus soluble in nonpolar environments like in choloroform but not soluble in polar environments like water.

What do lipids consist of?

Lipids have mainly hydrocarbons in their composition and are highly reduced forms of carbon. When metabolized, lipids are oxidized to release large amounts of energy and thus are useful to living organisms.

Where do lipids come from?

Lipids are molecules that can be extracted from plants and animals using nonpolar solvents such as ether, chloroform and acetone. Fats (and the fatty acids from which they are made) belong to this group as do other steroids, phospholipids forming cell membrane components etc.

Hydrolyzable/Non-hydrolyzable lipids

Lipids that contain a functional group ester are hydrolysable in water. These include neutral fats, waxes, phospholipids, and glycolipids.
Nonhydrolyzable lipids lack such functional groups and include steroids and fat-soluble vitamins (e.g. A, D, E, and K). Fats and oils are composed of triacylglycerols or triglycerides. These are composed of glycerol (1,2,3-trihydroxypropane) and 3 fatty acids to form a triester. Triglycerides are found in blood tests. Complete hydrolysis of triacylglycerols yields three fatty acids and a glycerol molecule. 

Fatty acids

Fatty acids are long chain carboxylic acids (typically 16 or more carbon atoms) which may or may not contain carbon-carbon double bonds.  The number of carbon atoms are almost always an even number and are usually unbranched.  Oleic acid is the most abundant fatty acid in nature. 

The membrane that surrounds a cell is made up of proteins and lipids. Depending on the membrane’s location and role in the body, lipids can make up anywhere from 20 to 80 percent of the membrane, with the remainder being proteins. Cholesterol, which is not found in plant cells, is a type of lipid that helps stiffen the membrane. Image Credit: National Institute of General Medical Sciences

Waxes/fats and oils

These are esters with long-chain carboxylic acids and long-alcohols. Fat is the name given to a class of triglycerides that appear as solid or semisolid at room temperature, fats are mainly present in animals. Oils are triglycerides that appear as a liquid at room temperature, oils are mainly present in plants and sometimes in fish.

Mono/poly unsaturated and saturated

Those fatty acids with no carbon-carbon double bonds are called saturated. Those that have two or more double bonds are called polyunsaturated.  Oleic acid is monounsaturated.

Saturated fats are typically solids and are derived from animals, while unsaturated fats are liquids and usually extracted from plants. 

Unsaturated fats assume a particular geometry that prevents the molecules from packing as efficiently as they do in saturated molecules. Thus the boiling points of unsaturated fats is lower.

Synthesis and function of lipids in the body

Lipids are utilized or synthesized from the dietary fats. There are in addition numerous biosynthetic pathways to both break down and synthesize lipids in the body.

There are, however, some essential lipids that need to be obtained from the diet. The main biological functions of lipids include storing energy as lipids may be broken down to yield large amounts of energy. Lipids also form the structural components of cell membranes and form various messengers and signalling molecules within the body.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)

Lipid Biological Functions

It is now known that lipids play a much more important role in the body than previously believed. It was previously known that lipids played the role of storage of energy or forming cell membranes alone. Researchers have found that lipids have a much more diverse and widespread biological role in the body in terms of intracellular signalling or local hormonal regulation etc.

Lipids are synthesized in the body using complex biosynthetic pathways. However, there are some lipids that are considered essential and need to be supplemented in diet.

In 1929, for example, George and Mildred Burr demonstrated that linoleic acid was an essential dietary constituent. Bergström, Samuelsson and others in 1964 added to the knowledge of role of lipids in the body by finding that essential fatty acid arachidonate was the biosynthetic precursor of the prostaglandins with their effects on inflammation and other diseases.

In 1979 the first biologically active phospholipid, platelet activating factor was discovered and there was a raised awareness regarding phosphatidylinositol and its metabolites in cellular signally and messaging.

Role of lipids in the body

Lipids have several roles in the body, these include acting as chemical messengers, storage and provision of energy and so forth.

Chemical messengers

All multicellular organisms use chemical messengers to send information between organelles and to other cells. Since lipids are small molecules insoluble in water, they are excellent candidates for signalling. The signalling molecules further attach to the receptors on the cell surface and bring about a change that leads to an action.

The signalling lipids, in their esterified form can infiltrate membranes and are transported to carry signals to other cells. These may bind to certain proteins as well and are inactive until they reach the site of action and encounter the appropriate receptor.

Storage and provision of energy

Storage lipids are triacylglycerols. These are inert and made up of three fatty acids and a glycerol.

Fatty acids in non esterified form, i.e. as free (unesterified) fatty acids are released from triacylglycerols during fasting to provide a source of energy and to form the structural components for cells.

Dietary fatty acids of short and medium chain size are not esterified but are oxidized rapidly in tissues as a source of ‘fuel”.

Longer chain fatty acids are esterified first to triacylglycerols or structural lipids.

Maintenance of temperature

Layers of subcutaneous fat under the skin also help in insulation and protection from cold. Maintenance of body temperature is mainly done by brown fat as opposed to white fat. Babies have a higher concentration of brown fat.

Membrane lipid layer formation

Linoleic and linolenic acids are essential fatty acids. These form arachidonic, eicosapentaenoic and docosahexaenoic acids. These for membrane lipids.

Membrane lipids are made of polyunsaturated fatty acids. Polyunsaturated fatty acids are important as constituents of the phospholipids, where they appear to confer several important properties to the membranes. One of the most important properties are fluidity and flexibility of the membrane.

Cholesterol formation

Much of the cholesterol is located in cell membranes. It also occurs in blood in free form as plasma lipoproteins. Lipoproteins are complex aggregates of lipids and proteins that make travel of lipids in a watery or aqueous solution possible and enable their transport throughout the body.

The main groups are classified as chylomicrons (CM), very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL), based on the relative densities

Cholesterol maintains the fluidity of membranes by interacting with their complex lipid components, specifically the phospholipids such as phosphatidylcholine and sphingomyelin. Cholesterol also is the precursor of bile acids, vitamin D and steroidal hormones.

Prostaglandin formation and role in inflammation

The essential fatty acids, linoleic and linolenic acids are precursors of many different types of eicosanoids, including the hydroxyeicosatetraenes, prostanoids (prostaglandins, thromboxanes and prostacyclins), leukotrienes (and lipoxins) and resolvins etc. these play an important role in pain, fever, inflammation and blood clotting.

The "fat-soluble" vitamins

The "fat-soluble" vitamins (A, D, E and K) are essential nutrients with numerous functions.

Acyl-carnitines transport and metabolize fatty acids in and out of mitochondria.

Polyprenols and their phosphorylated derivatives help on transport of molecules across membranes.

Cardiolipins are a subtype of glycerophospholipids with four acyl chains and three glycerol groups. They activate enzymes involved with oxidative phosphorylation.

Lipid Metabolism

Lipids are absorbed from the intestine and undergo digestion and metabolism before they can be utilized by the body. Most of the dietary lipids are fats and complex molecules that the body needs to break down in order to utilize and derive energy from.

Digestion of Lipids

Digestion of fats comprises of these major stages:-

  1. Absorption
  2. Emulsification of Fats
  3. Digestion of Fats
  4. Fat Metabolism
  5. Degradation

Absorption of lipids

Short-chain fatty acids (up to 12 carbons) are absorbed directly.

Triglycerides and dietary fats are insoluble in water and thus their absorption is difficult. To achieve this, the dietary fat is broken down into small particles that increases the exposed area for rapid attack by digestive enzymes.

Emulsification of Fats

Dietary fats undergo emulsification that leads to liberation of fatty acids. This is brought about by simple hydrolysis of the ester bonds in triglycerides.

Fats are broken down into small particles by detergent action and mechanical mixing. The detergent action is performed by digestive juices, but especially by partially digested fats (fatty acid soaps and monacylglycerols) and by bile salts.

The bile salts such as cholic acid contain a side that is hydrophobic (repellent to water) and another water loving or hydrophhillic side. This allows them to dissolve at an oil-water interface, with the hydrophobic surface in contact with the lipid to be absorbed and the hydrophilic surface in the watery medium. This is called the detergent action and this emulsifies fats and yields mixed micelles.

Mixed Micelles serve as transport vehicles for less water soluble lipids from food and also for cholesterol, fat-soluble vitamins A, D, E, and K.

Digestion of Fats

After emulsification the fats are hydrolyzed or broken down by enzymes secreted by the pancreas. The most important enzyme involved is pancreatic lipase. Pancreatic lipase breaks down primary ester linkages, the 1 or the 3 ester bonds. This converts triglycerides to 2-monoglycerides (2-monoacylglycerols). Less than 10% of triglycerides remain unhydrolyzed in the intestine.

Fat Metabolism

Short chain fatty acids enter the circulation directly but most of the fatty acids are reesterified with glycerol in the intestines to form triglycerides that enter into the blood as lipoprotein particles called chylomicrons.

Lipoprotein lipase acts on these chylomicrons to form fatty acids. These may be stored as fat in adipose tissue, used for energy in any tissue with mitochondria using oxygen and reesterified to triglycerides in the liver and exported as lipoproteins called VLDL (very low density lipoproteins).

VLDL has a similar outcome as chylomicrons and eventually is converted to LDL (low density lipoproteins). Insulin simulates lipoprotein lipase.

During starvation for long periods of time the fatty acids can also be converted to ketone bodies in the liver. These ketone bodies can be used as an energy source by most cells that have mitochondria.

Degradation

Fatty acids are broken down by Beta oxidation. This occurs in the mitochondria and/or in peroxisomes to generate acetyl-CoA. The process is the reverse of fatty acid synthesis: two-carbon fragments are removed from the carboxyl end of the acid. This occurs after dehydrogenation, hydration, and oxidation to form a beta-keto acid.

The acetyl-CoA then converts to ATP, CO2, and H2O using the citric acid cycle and releases energy of 106 ATP. Unsaturated fatty acids require additional enzymatic steps for degradation.

Lipid Health and Nutrition

Lipids play diverse roles in the normal functioning of the body:

  • they serve as the structural building material of all membranes of cells and organelles
  • they provide energy for living organisms - providing more than twice the energy content compared with carbohydrates and proteins on a weight basis
  • they function as molecular messengers and signalling molecules in the body

Lipids are also biomarkers of disease and are involved in several pathological conditions. Lipids are also known to play a role in genetic modification and influence risk of chronic disease.

Dietary lipids

Some of the fatty acids need to be taken in diet. This includes essential fatty acids (EFAs), linoleic acid (LA, an omega-6 fatty acid, 18:2n-6), and a-linolenic acid (LNA, an omega-3 fatty acid, 18:3n-3). These help in formation of polyunsaturated fatty acids (PUFAs) used in cellular structures and as precursors for the biosynthesis of many of the body’s regulatory molecules like long-chain PUFAs, arachidonic acid,  eicosapentaenoic acid (EPA, 20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3) and eicosanoids. DHA again is necessary for normal neural and retinal development in the infant and young child.

Effects of PUFA

Dietary lipids help in biochemical and physiological functions as modulators of cell actions and genes. For example, the n-6 and n-3 PUFAs bind to the peroxisome proliferator-activated receptors (PPARs) on genes. This PPAR gene is important for lipid and carbohydrate metabolism. These also play a role in chronic diseases like diabetes and inflammatory conditions.

PUFA in diet has been found to reduce risk of cardiovascular disease and cancers. In addition, n-3 fatty acids are known to lessen the severity and minimize symptoms of chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, and may even benefit in correcting psychological disorders.

PUFAs modulate eicosanoid biosynthesis in various tissues and cell types and this can influence gene expression.

Foods with PUFA

PUFA is present in three forms in food. These are LNA in vegetables, oilseeds, and nuts, and EPA and DHA in cold water fishes and algae.

SDA is rich in plant oils (such as hempseed oil and black currant seed oil) but can be isolated and concentrated from marine fish. Since n-3 fatty acids cannot be synthesized in the body they must be either ingested directly or formed from LNA.

Food supplements and fortification

The diet needs to be low in saturated fats. Essential fatty acids and n-3 PUFA, however, are important in the diet.

Sources of n-3 PUFAs are also added directly to infant formula to provide sufficient DHA for normal development of the nervous system during early infancy. These supplements are added to both dairy and non dairy products to reduce risk of heart disease, cancer risk and risk of obesity. The n-3 PUFA are contained and added in fish meal, fish oil, vegetable oils, linseed oil and canola oil etc.

Lipids and vitamins

A minimum amount of dietary fat is important because it helps in absorption of fat-soluble vitamins (A, D, E and K) and carotenoids.

Lipids and chronic diseases

Fats in diet play a role in chronic diseases. Up to 70% of all cancers in the United States are attributable to diet for example. Around half of the population according to the USDA develops a diet-related chronic disease responsible for the leading causes of death like heart disease, cancer, stroke, diabetes, and arteriosclerosis. This raises the annual health costs to $250 billion in the USA. High fat, especially trans fats and unsaturated fats lead to heart disease, degenerative and inflammatory arthritis, osteoporosis, obesity, cancer etc.