Group 2 LIPIDS: CHEMISTRY, STRUCTURE, CLASSIFICATION, FUNCTION, AND DIGESTION Chua, Jenalynne Mareah O., Dela Cruz, Richard Dean Clod C., Fernandez, Mia Allyanna A., Gutierrez, Meliz Iren Kaye, R., Lingan, Josephine Estelle, C., Neria, Allison Chloe C. Reyes, Ma. Sophia Graciela L. & Torres, Javier A. College of Public Health, University of the Philippines Manila PH 161 Biochemistry, Dr. Palaruan

I. Chemistry

A. Definition

Lipids are a class of chemically diverse biomolecules that are generally non-polar; they are insoluble in water but soluble in organic solvents. Because they are non-polar, they can be extracted by non-polar solvents. They are also known as basically any fatty acid and their derivatives, or any substance biosynthetically or functionally related to them. In general, they are for storage (fatty acids and oils), for use as structural components of biological membranes (phospholipids and steroids), and as enzyme cofactors, electron carriers and pigments among others.

B. Characteristics

Lipids are generally amphipathic due to

having two parts: one hydrophobic and one hydrophilic. Usually the long fatty acid tails tend to be nonpolar, so they are not soluble in the more polar water, making it seem like they avoid water. Hence, these are known to be hydrophobic. The head on the other hand, is the opposite, for it tends to be polar and thus, love water. Hence, they are known to be hydrophilic. Lipids are also known to have high energy value since they generate more energy (9kcal) for every 1g of fat as compared to proteins and carbohydrates which only generates 4 kcal. In the body, they have a variety of functions such as helping store fat-soluble vitamins ( A, D, E, K) in liver and fatty tissues. They are found in subcutaneous tissue for thermal insulation and act as cushions as well for internal organs. Plus, they are also found in myelin sheaths which serve as nerve insulator. However, lipids dont just remain stagnant in the body, some help with transport. For example, chylomicrons are used to transport fat from the intestines to other locations. High density lipoprotein (HDL), the good cholesterol, transports fat into the liver. Low density lipoproteins (LDL), the bad cholesterol, transport the fat into the peripheral vessels where they tend to build up. In the

cellular level, lipids constitute the phospholipid bilayer.

II. Structure

Lipids as mentioned above are amphipathic, and therefore, have both polar and nonpolar ends. However, generally, it is predominantly nonpolar. But, because they are variable, lipids may be classified according to their structure.

Fatty Acids consists of a carboxylic acid and a long unbranched hydrocarbon chain, and are actually precursors to more complex lipids. It is often found as the hydrocarbon tail component of many lipids. Usually, almost all fatty acids have an even number of carbon atoms, and their classification can be further subdivided into saturated or unsaturated fatty acids.Saturated fatty acids have no double (C=C) bonds as seen in Figure 1.

Figure 1. Saturated fatty acids

Unsaturated fatty acids, on the other hand, have the double bond/s. Because of the double bond, the linearity seen in the saturated hydrocarbon chain isnt seen here. Instead, there are kinks or bends in the chain which gives the unsaturated fatty acid either a cis or trans configuration (figure 2).

Figure 2. Unsaturated fatty acids Another classification of lipids according to their structure is waxes. Waxes have esters with long hydrocarbon chains on both ends (figure 3). They are known to function as water barriers.

Figure 3. Wax

Triacylglycerides consists of a nonpolar carboxylate of fatty acids and a polar hydroxylate ion of glycerol (figure 4). They are known to function as storage for energy.

Figure 4. Triacylglycerol condensation

Phospholipids are composed of glycerol esterified with two fatty acids and one phosphate group as shown in (figure 5). These are commonly found in cell membranes.

Figure 5. Structure of a phospholipid

Prostaglandins are basically cyclic fatty acid components that usually function as regulators and signal molecules as in uterine contraction. An example in Figure 6 shows a prostaglandin with a 5-carbon ring.

Figure 6. Prostaglandin Steroids are seen to exhibit a ring system of three adjacent cyclohexanes and a single cyclopentane. Gonane an example of a steroid is shown in the figure below.

Figure 7. Gonane

III. Classifications

A. Precursors to Lipids

Precursors of lipids are the molecules that structurally make up a lipid molecule (Murray, 2003). There are three known precursors which are fatty acids, glycerol, and the hydrocarbon chain. Fatty Acids are building blocks composed of C, H, O arranged in chains carrying terminal carboxyl -COOH which gives the acidic properties of the molecule. Glycerol or Glycerine is a simple polyol with three hydroxyl -OH groups. It serves as the backbone of the triglycerides or fats. Hydrocarbon is an organic compound consisting entirely of hydrogen and carbon. They can be classified as either alkanes having no double bonds, alkenes having two double bonds, and alkynes having triple bonds. the unsaturation and saturation of fats are dictated by the presence or absence of these double bonds.

B. Simple Lipids

Simple lipids are fatty acid esters with alcohols, and can be further classified into two: triacylglycerides and waxes.

Triacylglycerols, also known as triacylglycerides, triglycerols or triglycerides, and more commonly known as fats, are esters of fatty acids with the alcohol glycerol. They are usually solid in room temperature, and are stored in animals as fat droplets in specialized vertebrate fat cells called adipocytes, whereas in plants (particularly seed or plant cells) are stored as oil, which is the liquid state of fats at a higher temperature. They are the most abundant lipids in nature, and are one of the three main macronutrients besides carbohydrates and proteins. They are either simple (in which the three fatty acid radicals are identical or similar) or mixed (unidentical fatty acid components). Many natural fats found in foods are complex mixtures of simple and mixed triacylglycerols.

Triacylglycerols can also be classified

further according to the structure of its chemical bonds; they can be saturated (without any double bonds), or unsaturated (with double bonds). Saturated fats are animal in origin, solid at room temperature and are saturated with hydrogen atoms (which prevents carbon from forming more double or triple bonds), while unsaturated fats have a lower cholesterol layer, and are more commonly seen as plant oils. Unsaturated fats can be further subdivided according to the number of double bonds the fatty acid chains have: they can be monounsaturated, where there is only one double bond present, and polyunsaturated, with numerous double bonds. The former type solidifies when chilled, while the latter stays liquid.

Waxes are esters of long-chain fatty acids with long-chain monohydroxy alcohols having higher molecular weight. They are solid, with a generally higher melting point than triacylglycerols. They are also water repellant, with a firm consistency. Waxes are secreted by birds (particularly by their preen glands) to make their feathers water repellant. They are also used as a thick coating for plant leaves, which protects from evaporation and from parasites. They are the chief storage form of metabolic fuel in plankton, and are used in manufacture of lotions, ointments, and polishes.

C. Compound Lipids

Complex lipids result from the

esterification of fatty acids which have additional groups and an alcohol which is a phosphoric acid residue (Murray, 2003). This group of lipids can be further classified into two subgroups: phospholipids and glycolipids which are both amphipathic lipids, containing polar and nonpolar ends, which can be usually found in the membranes of the cells.

Phospholipids got their name from the

phosphate ion that is one of their components, which is used in their formation. There are two subdivisions under phospholipids and they are classified depending on their parent compound. The first group is the glycerophospholipids which have phosphatidic acid as their parent compound through the process of esterification of the phosphoric acid residue (Stenesh, 2013). These result from the combination of glycerol, two fatty acids, a phosphate group, and an alcohol. Glycerophospholipid are usually found in cell membranes wherein their main function is for the support of the structure and the permeability of the cell. The other group would be the sphingophospholipid which is formed from ceramides through double esterification of the phosphoric acid (Stenesh, 2013). In contrast to the previous group, sphingophospholipids result from the combination of sphingosine (the parent compound), a fatty acid, a phosphate group and an alcohol. They are abundant in the brain, primarily the nervous tissues which are myelinated, for they are the main component of sphingomyelin which wraps around the axons of neurons contributing to the efficiency of the nerve impulse conduction. One of the major differences between glycerophospholipids and sphingophospholipids would be their backbones. The former has a glycerol backbone while the latter has a sphingosine backbone. Moreover, the former has an ester bonding pattern while the latter has an amide bonding pattern. Glycolipids are lipids that contain a fatty acid, sphingosine and a carbohydrate (Murray, 2003). Glycolipids have a sugar residue that can be a monosaccharide, disaccharide, oligosaccharide or a polysaccharide. They

also do not have a phosphate group. Just like phospholipids, the glycolipids are further subdivided into two groups: glyceroglycolipids which have a glycerol backbone and sphingoglycolipid which have a sphingosine backbone. Glyceroglycolipids are found in the nervous system in the form of a cerebroside, particularly the galactocerebroside of the brain and the peripheral nervous system.Sphingoglycolipids, on the other hand, are also found in the plasma membrane and the sphingomyelin. An autoimmune disease called the Tay-Sachs disease occurs when harmful quantities of sphingoglycolipids accumulate in the nerve cells of the brain. It is also called sphingolipidosis. It is actually a genetic disorder, fatal in its most common variant known as Infantile Tay-Sachs disease. It is inherited in a recessive pattern. Glycolipids are actually found in the blood as they act as receptors at the surface of the red blood cell.

Another classification under complex lipids is those which have both lipids and proteins in their structures. They are usually called the lipoproteins. They usually function as enzymes, transporters, structural proteins, antigens, adhesins and toxins. A common example would be the high and low density lipoproteins which are actually transporter of fats to be carried in the blood stream. High levels of lipoproteins, particularly the low density lipoproteins can increase the rate of heart disease, atherosclerosis. The disease results from the blockage of the blood flow in the blood vessel because of the accumulation of fat, thus increasing the chances of suffering from stroke or heart attack.

D. Derived Lipids

Derived Lipids are derived from simple and compound lipids via hydrolysis (Murray, 2003). Some of these are steroids, hormones, fatty aldehyde, ketone bodies, and lipid-soluble vitamins.

One of the most common derived lipid are

the steroids and some hormones. Steroids are flat molecules with four interlocking rings and has no fatty acid tail. One of the important steroids of the body is cholesterol. Cholesterol may either be HDL or LDL. Hormones such as

sex hormones testosterone, estrogen and progesterone are also classified under steroids. Another steroid is one of the lipid-soluble vitamins, Vitamin D. Steroids are oftentimes used for promotion of growth of muscles; these are called Anabolic-androgenic steroids. Once ingested or injected, steroids travel in the bloodstream to the skeletal muscles where they bind with androgen receptors (NIH, 2012). They react with the DNA of the cells and stimulate protein synthesis which leads to increase in cell size or muscle hypertrophy. It should be noted however, that the cell number does not increase,

Another type of derived lipid is fatty aldehydes which are aldehydes with fatty aliphatic eight or more carbon membered chain attached (Murray, 2003).

Ketone Bodies are three water-soluble molecules namely acetone, acetoacetic acid, beta hydroxy-butyric acid produced by the liver when the glucose level of body is low in level, which occurs in instances such as during low food intake or fasting, as sources of energy. Ketone bodies are toxic and acidic, therefore, a considerable increase in level of these molecules in the blood may be harmful and may cause homeostatic imbalances. Ketosis is condition when there is a presence of ketone bodies in the blood (Marieb, 2014). Ketonuria is the presence of ketone bodies in urine. Some can be expelled through urination. Acetone on the other hand can be released out of the body via respiration.

Lipid-soluble vitamins are essential micronutrients needed by the body is small amount for proper functioning. These are fat soluble vitamins are A, D, E, K usually stored in liver and adipocytes.

IV. Functions

A. Storage lipids

Triacylglycerols or fats provide stored energy in the form of adipocytes in vertebrates and oils in plant seeds. Triacylglycerols as a source and storage of energy is more advantageous than polysaccharides like starch and glycerol due to two main reasons: (1) the oxidation of triacylglycerols yield more than two times energy, 9 kcal/gram as compared to carbohydrates and proteins 4 kcal/gram; and (2) triacylglycerols are unhydrated and thus,

lighter to carry for the organisms (Nelson & Cox, 2008).

B. Lipids as insulators

1. Thermal Insulation Triacylglycerols stored under the skin as

part of the subcutaneous tissue helps keep the internal body temperature regular despite sudden changes in the external temperature. Warm-blooded polar animals survive in the arctic regions because of a thick layer of fat under their skin. Also, in hibernating animals, huge fat reserves serve as insulation as well as energy storage.

2. Electrical Insulation Myelin, a membranous sheath composed

mainly of sphingolipids (sphingomyelin), envelops and insulates the axons of most neurons (Nelson & Cox, 2008). Myelinated nerves transmit impulses faster than unmyelinated nerve fibers, a mechanism known as saltatory conduction.

C. Source of fat-soluble vitamins like A, D,

E, K.

These vitamins are made up of isoprene units. All of them play essential role in the metabolism or physiology of animals.

1. Vitamin A - furnishes the visual pigment of the vertebrate eye and is a regulator of gene expression during epithelial cell growth

2. Vitamin D - precursor to a hormone that regulates calcium metabolism

3. Vitamin E - protects the membrane lipids from oxidative damage

4. Vitamin K - essential in the blood-clotting process

D. Lipids as protection

Waxes have water-repellent properties and

have firm consistency. To illustrate this, certain skin glands of vertebrates secrete waxes to protect hair and skin to keep it lubricated and waterproof. Birds, particularly the waterfowl, secrete waxes from their preen glands to keep their feathers water-repellent. Also, the shiny leaves of many tropical plants are coated with waxes which prevents water loss and protects against parasites.

Biological waxes (e.g. Lanolin, beeswax, carnauba wax and wax extracted from the spermaceti oil) are widely used in manufacture of lotions, ointments, and polishes (Nelson & Cox, 2008).

E. Structural lipids in cell membrane 1. The polar lipids, with polar heads and

nonpolar tails, are important component of cell membrane structure (membrane permeability).

2. Sphingolipids at cell surfaces are sites of biological recognition. (e.g. Glycosphingolipids as determinants of blood groups O, A, B). Human blood groups (O, A, B) are determined in part by the oligosaccharide head groups of these glycosphingolipids. The same three oligosaccharides are also found attached to certain blood proteins of individual blood types O, A, B, respectively.

3. Cholesterol, the major sterol in animals, is both a structural component of membranes and precursor to a wide variety of steroids. Sterols are structural lipids present in the membranes of most eukaryotic cells. Meanwhile, cholesterol is the major sterol and is the component of the fat-soluble vitamins. Aside from being membrane constituents, sterols serve as precursors for a variety of products. They are the steroid hormones which regulate gene expression and the bile acids which emulsify fats. (Nelson & Cox, 2008).

F. Lipids as signals

Some lipids like prostaglandins and steroid

hormones act as cellular metabolic regulators and play major roles in the control of the bodys homeostasis. The male and female sex hormones, estrogen, progesterone and testosterone, as well as the hormones produced by the adrenal cortex, cortisol and aldosterone are derived from sterols. Prostaglandins, thromboxanes, and leukotrienes are derived from arachidonate and aid in inflammatory response and other body mechanisms (Nelson & Cox, 2008). Prostaglandins play a role in the generation of inflammatory response as their increased number contribute to the development of the cardinal signs of acute inflammation (Ricciotti & FitzGerald, 2011). Thromboxanes, a

six-membered ring containing an ether, are produced by platelets and aid in blood clot formation. Leukotrienes, on the other hand, act as powerful biological signals by acting in allergic and inflammatory reactions by promoting vasodilation, increasing vascular permeability and in smooth muscle contraction (cs.stewards.edu, 2015).

V. Lipid Digestion

Lipids found in the average human diet are needed to be hydrolyzed and emulsified to smaller micelles before they can be absorbed by the mucous epithelium in the intestine. The majority of these lipids are triacylglycerols, but other forms of lipids such as fat-soluble lipids, phospholipids and cholesterols are also emulsified within the micelles.

Fats consumed tend to go down as big

blobs in the digestive tract and a majority are only emulsified in the intestines. The process starts at the mouth with the hydrolysis of little of the triacylglycerols into 1,2-diacylglycerols by lingual lipases (Murray, 2013). This occurs yet again in the stomach but with gastric lipases. Once the fat reaches the duodenum, the pancreas secretes pancreatic lipase and acts together with colipase to hydrolyze the triacylglycerols into 2-monoacylglycerols. However, it is noted that due to the difficulty of hydrolyzing monoacylglycerols, only less than 25% are fully hydrolyzed into glycerol and fatty acids.

When the gallbladder secretes bile, the lipid

digestion products may be emulsified into micelles together with the phospholipids cholesterol and fat-soluble vitamins. This is why an extremely low fat diet will result in the impairment of absorption of fat-soluble vitamins. The micelles made from the emulsified lipid digestion products are essential in its transport through the aqueous environment of the intestinal lumen. Once the micelles are in close contact with the brush border mucous epithelium of the intestine,especially that of the jejunum, they are then uptaken into the epithelium where the glycerol and fatty acids are re-acylated into triacylglycerols through the monoacylglycerol pathway.

The glycerol left in the intestinal lumen are

not re-acylated but remain unused and are just passed into the portal vein while the bile salts

are absorbed into the ileum and into the enterohepatic circulation (Murray, 2003). As for the glycerol and fatty acids successfully re-acylated, they are secreted as chylomicrons with the other products of lipid digestion into the lymphatic channel and eventually to the blood stream through the thoracic duct.

VI. Other Information

A. Spermaceti Organ of sperm whales

The size of the sperm whales head is largely due to a blubbery mass called the spermaceti organ. It makes up 90% of the head weight, containing up to 4 tons of spermaceti oil, which is a mixture of triacylglycerol and wax. Spermaceti oil contains lots of unsaturated fatty acids, and is liquid at normal body temperature but solidifies at lower temperatures. Its ability to solidify and liquefy depending on the body temperature has an effect on the whales buoyancy, which allows it to withstand high pressure while diving deep into the ocean for food. (Nelson & Cox, 2015)

B. Inheritable Human Disease

The sphingolipids present in the nervous system can be broken down by hydrolytic enzymes in lysosomes. However when these enzymes have defects, partial breakdown products accumulate in tissues and can cause serious damage, resulting in inheritable human diseases such as the Tay-Sachs Disease. The collective term for these disorders in lipid breakdown is sphingolipidoses. (Nelson & Cox, 2015)

References:

Marieb, E.(2014). Human anatomy and physiology (10th ed.). Pearson Education. Hallare, A. (n.d.) Student handbook for general zoology. University of the Philippines Manila. Leukotrienes and Lipoxins. Retrieved from http://www.cs.stedwards.edu/chem/Chemistry/CHEM43/CHEM43/Leukotr/FUNCTION.HTML Murray, R. et. al. (2003). Harpers Illustrated Biochemistry, 26th Edition. McGraw-Hill Companies. National Institute on Drug Abuse (2015). Steroids. Retrieved 6 September 2015 from

http://www.drugabuse.gov/publications/drugfacts/anabolic-steroids Nelson, D. & Cox, M. (2008). Lehninger Principles of Biochemistry, 6th Edition. New York : W.H. Freeman. Ricciotti, E., & FitzGerald, G. A. (2011). Prostaglandins and Inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(5), 9861000. http://doi.org/10.1161/ATVBAHA.110.207449 Stenesh, J. (2013). Biochemistry. USA: Springer Science and Business Media.

I hereby certify that I have given substantial contribution to this report.

Chua, Jenalynne Maraeh O.

Dela Cruz, Richard Dean Clod C.

Fernandez, Mia Allyanna A.

Gutierrez, Meliz Iren Kaye, R.

Lingan, Josephine Estelle, C.

Neria, Allison Chloe C.

Reyes, Ma. Sophia Graciela L.

Torres, Javier A.