Understanding the classification of Lipids


(In this topic you can find the answer to Question L-02

Lipids are a diverse group of compounds that can be extracted from biological material using non-polar solvents. They are not soluble in water and other polar solvents. (Some lipids are amphipatic, though, since a part of the molecule is hydrophobic, while the other part is hydrophilic).

 

As you can see, the definition of lipids is not a structural concept, but a functional one. It explains that lipids are very different from the structural point of view.

Different kind of lipids

Different kind of lipids

    Anyway, since some of them show structural similarities, these are used to form the different subclasses or these compounds. 
  
According to specific structural similarities, lipids are classified in the following subgroups: 
 
 

 

 

 

 

      Fatty acids

      All of them are carboxylic acids with a hydrocarbon chain usually lineal. Natural fatty acids generally have an even number of carbon. They can be saturated or unsaturated, essentials or no essential, cis or trans (you can find the different criteria for the classification of fatty acids in this post)

 

Acyl glicerols or Neutral Fats

      They are esters of fatty acids with glycerol. Depending on the number of fatty acids that are esterified to the glycerol, they can be sub classified as monoacylglycerols, diacylglycerols and triacylglycerols.

 

Waxes

      From the structural point of view, they are esters of fatty acids with an alcohol different from glycerol. From the biomedical point of view, the only important waxes are the cholesterol esters (but nobody called them “waxes”!).

 

Phosphoglycerides 

      The structural backbone of this group of lipids is the phosphatidate: esters of diacylglycerols with phosphoric acid. This group includes lecithins, cephalines, phosphatidyl inositols and other important compounds. (In this link you can find a description of the different sub classes of phosphoglycerides and their functions)

 

Sphingolipids

      Lipids belonging to this group have in common the alcohol sphingosin in their structure. Some sphingolipids, like sphingomyelin, are linked to phosphatated groups (sphingomyelin and phosphoglycerides are called phospholipids).  Other sphingolipids do not have phosphate, but they are linked to carbohydrates, forming the glycosphingolipids. The intracellular accumulation of sphingolipids because of genetic deficit of enzymes related to their metabolism, produce diseases called sphingolipidoses. These conditions include Tay-Sachs disease, Niemann- Pick disease, Fabry’s Disease, Gaucher’s disease, etc. depending on the missing enzyme and/or the kind of sphingolipid that is accumulated.

 

Isoprenoid Lipids:

      These lipids have in common that they are formed by isoprene units (methyl butadiene). In some cases, the presence of isoprene is obvious in the structure, like in the terpens (Vitamin A, Vitamin E, Coenzyme Q). In other cases, the isoprene units are evident in the process of synthesis, like in the biosynthesis of steroids, the other important group of isoprenoid lipids.

 

Eicosanoid Lipids:

      These lipids are derivative of Arachidonic acid, an unsaturated fatty acid with 20 carbons (Eico is the Greek prefix for twenty, in the same way that deca means ten and penta indicates five). This group includes prostaglandins, leukotriens and thromboxans.

 

 

A (L-04): Phosphoglycerides aka Glycerophospholipids aka Phosphoacylglycerols


 

Answer to Question L-04 about Lipids. 

 

Answer (e): Phosphoglycerides.

 

Phosphoglycerides,  Glycerophospholipids aka Phosphoacylglycerols can be defined as amphipatic lipids formed by esters of acylglycerols with phosphate and another hydroxylated compound. 

 

 

Structure

 

General structure of Phosphoglycerides

   

                                                                        phosphoglyceride general structure

 

The two acyl groups appear in the orange area, linked to the glycerol (in the white area) by ester (carboxylic ester) linkages. The hydrocarbon chain of the acyl groups represents the hydrophobic or apolar part of these molecules. In the green area, appears the Phosphate linked through a phosphoric ester linkage to the glycerol, but also to X, the hydroxylated compound whose OH group has formed an ester linkage with the Phosphoric acid (Phosphate, at physiological pH). This is the polar part of the molecule.

 

Depending on the identity of X, the phosphoglyceride can be:

 

         Phosphatidate  (if X is an Hydrogen)

         Phosphatidyl choline aka lecithin (if X is choline)

         Phosphatidyl ethanolamine (if X is ethanolamine)

         Phosphatidyl serine (if X is serine)

         Phosphatidyl glycerol (if X is another glycerol)

         Phosphatidyl inositol  (if X is inositol)

         Cardiolipin  (if X is a glycerophosphatidate)

 

In the group of Phosphoglycerides are also included other compounds that do not have the Phosphatidyl structure, since these compounds have linked to the C1 of glycerol an alkyl side chain bound through an ether linkage, instead of the acyl side chain linked through an ester linkage, characteristic of the phosphatidyl group.  These compounds are known as Ether lipids. The most important representatives of this kind of phosphoglycerols are Plamalogens and Platelet Activating Factor.

 

                       Plasmalogen

 

                                      plasmalogen structure

 

                 Platelet activating factor

 

                                     platelet activating factor structure

 

 

Functions:

 

 

The functions of phosphoglycerides include:

 

         Structure of cell membranes

         Reservoir for intracellular messengers

         Anchors of some proteins for cell membranes

         Stabilization of protein structure

         Cofactors of enzymes

         Biological detergents

        Surfactants in lungs

        Solubilization of non polar lipids in lipoproteins.

 

 

The individual role of the main phosphoglycerides is described below:

 

Phosphatidic acid: Metabolic intermediary and precursor in the synthesis of other phospholipids and triacylglycerol. It has been implicated in signaling process, when released from other phospholipids by the action of phospholipase D (Phosphatidic acid and related lipids)    

 

Phosphatidyl glycerol: It is a component of membranes, and the main phospholipid component in certain bacteria. In human tissues it is found mainly in mitochondria. It is also the second most abundant phospholipid in lung surfactant and is a precursor of cardiolipin.

 

Phosphatidyl ethanolamine (cephaline) is the second most abundant phospholipid in animals. It has a key role in the structure of membranes, with a specific role in stabilizing the structure of some proteins, allowing them a transporting or enzymatic function in or at the membrane. (Phosphatidyl ethanolamine and related lipids.)

 

Phosphatidyl Choline is the most abundant phospholipid in animals and is the key building block of membranes. It is also the main phospholipid of plasmatic lipoproteins. The role of phosphatidyl choline as lung surfactant and its medical implications have been discussed in other post.  Phosphatidyl choline may have a role in the signaling system especially in the nucleus, by generating diacylglcycerol under the action of phospholipases C and/or D. (Phosphatidyl Choline and related lipids)

 

Phosphatidyl Serine is located mainly in the inner surface of the plasma membrane. It is a required cofactor of protein Kinases C and other enzymes and consequently has an important role in the intracellular signaling system, and participates in coagulation, apoptosis and mineral deposition in bones.   (Phosphatidyl serine: structure, occurrence, biochemistry and analysis)

 

Phosphatidyl inositol and phosphorylated derivatives are important phospholipids with roles in the cellular signaling system, in the synthesis of eicosanoids, as a component of membranes and as membrane anchors for protein. The most important phosphorylated derivatives are phosphoinositol 4 (P) and Phosphoinositol 4, 5 diphosphate.

 

The key role of phosphatidyl inositol 4,5 diphosphate in the Phospholipase C system, yielding different second messengers, has been described elsewhere in this site. Phosphatidyl inositol is the main source of arachidonate in peripheral tissues. (Arachidonate is the precursor of the eicosanoid lipids prostaglandins, leukotrienes and thromboxanes).

 

Cardiolipin is a very important phospholipid in mitochondrial membrane. It is particularly abundant in heart tissue, where it was discovered. Most of the cardiolipin in humans have four linoleyl groups in its structure. Cardiolipin appears almost exclusively in the inner membrane of the mitochondria, where it interacts with various proteins. It has been demonstrated that cardiolipin is necessary for the activity of different enzymes, including enzymes of the respiratory chain. Cardiolipin apparently participates also in steroidogenesis, apoptosis, regulation of gene expression and the minor quantities found in plasmatic lipoproteins have anticoagulant functions.

 

Barth Syndrome, a cardiomyopathie in children, is associated to the deficit of tafazzin, a phospholipid acyltransferase that participates in the remodeling of cardiolipin (e.g. in the introduction of specific fatty acids during the synthesis).  Children with this X-linked disease have decreased quantities of tetralinoleyl cardiolipin and apparently, it is translated as a reduction in the efficiency of the respiratory chain in the heart muscle.(Cardiolipin: Structure, occurrence, biology and analysis.pdf)

 

Plasmalogens: Structure of membranes, where they act as reservoirs of polyunsaturated fatty acids that may act as intracellular signaling compounds.

 

Platelet Activation Factor: This lipid is not stored in a preformed state, but synthesized when necessary as a response to inflammatory process. It is one of the most potent bioactive molecules known, causing effects at concentrations as low as 10 -12 mol/L.  It participates in the signaling process activating cytoplasmatic Phospholipases A and C.  Phospholipase C produces a release of Ca++ and activation of Protein Kinase C (see related post). It has proinflammatory properties and has been implicated in the pathogenesis of different diseases, from allergic to thrombotic conditions. (Platelet Activating Factor, Chemistry and Biology.)

 

 

For more information about Glycerophospholipids, check:

 

Complex glycerolipids in http://www.lipidlibrary.co.uk/Lipids/complex.html

 

 

Phosphoglycerides in Cyberlipid center: http://www.cyberlipid.org/phlip/pgly02.htm#1

 

 

 

 

Understanding Fatty acids Classification


 

Answer to Biochemistry Question about Lipids (L-03)

 

Answer: (f)

 

PALMITIC ACID

 

CH3-CH2 -CH2– CH2– CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COOH

 

Another notation: CH3-(CH2 )14 – COOH

 

Another notation: C16:0 (It means, 16 carbons, no double bonds)

 

Palmitic acid or hexadecanoic acid is a 16 carbon fatty acid,  It is the most common fatty saturated acid found in plants and animals (no the most abundant, though). It was purified from Palm oil, and it was named after it. Humans can synthetize it, so it is non essential.

 

FATTY ACIDS CLASSIFICATION

 

 

Fatty acids are carboxylic acids derived or contained in lipids. They show the general formula

 

R-COOH  (R-COO- for free fatty acids at physiological pH)

 

Where R is usually a lineal (unbranched) carbon chain with an even number of carbons.(Funny mistake found in different textbooks…when you think about it, R has an odd number of carbons, so the fatty acid (R + COOH) has an even number of Carbons)

Natural fatty acids usually contain 4 to 28 carbons (Most of the fatty acids in complex lipids contain 14 to 22 carbons, though).

 

The function of fatty acids are:

 

            Biological fuel

 

            Components of more complex lipids

 

There are multiple classifications of fatty acids. The most used, from the biomedical point of view are:

 

CHEMICAL: According to the presence of double bonds in the carbon chain:

 

         Saturated (no double bonds)

 

            CH3-CH2– CH2– CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COOH

 

         Unsaturated (one or more double bonds)

 

            CH3– CH2– CH=CH-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COOH

 

According to the numbers of double bonds

 

        monounsaturated (just one double bond)

 

                        CH3– CH2– CH=CH-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COOH

 

        polyunsaturated. (more than one double bond)

 

                        CH3– CH2– CH=CH-CH2-CH=CH-CH2-CH2-CH2-CH2-COOH

 

 

According to the position of the double bond relative to the last carbon of the chain (sometimes called Metabolic classification)

 

          Omega 3 (the double bond nearest the last carbon of the chain (Cw)  is 3 carbons apart from the end of the chain)

 

                         CH3– CH2– CH=CH-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COOH

                       

           Omega 6 (the doble bond nearest to the last carbon of the chain is 6 carbon apart)

 

                        CH3– CH2– CH2-CH2-CH2– CH=CH-CH2-CH2-CH2-CH2-CH2-CH2-COOH                

 

According to the geometric configuration

 

          Cis fatty acids (both part of the chain adjacent to the double bond are at the same side of the double bond)

 

          Trans fatty acids (the two parts or the chain adjacent to the double bond are in opposite side or the double bond)

 

 

                                            Trans and cis fatty acids

 

 

BIOLOGICAL (also called Nutritional classification)

 

         Essential: Non synthesized by animals. Should be obtained from the diet. Linoleic and Linolenic.

 

         Non essential: Synthesized by animals.  All the others.

 

ACCORDING TO THE NUMBER OF CARBONS:

 

There are different classifications based on the number of carbons

 

Short chain fatty acids: 2 to 6 carbons

Medium Chain: 8 to 14 carbons

Long Chain fatty acids: 16 carbons and up.

 

 

Another classification based on the number of carbons:

 

Short chain  2-4 carbons

Medium chain 6-12 carbons

Long chain 14-22 carbons

Very long chain 24 -26 carbons

 

Some texts differ in relation to exactly how many carbons a fatty acid should have for belonging to one of these groups. For example, some texts consider a Fatty acid with more than 20 C as a VLCFA,

 

 

Only when we know these classifications we are able to understand plently expressions like:

 

“Saturated fatty acids and trans fatty acids increase cholesterol concentration in blood, while unsaturated fatty acids decrease it.”

 

“Oils are rich in unsaturated fatty acids”

 

“Medium Chain Acyl Co A Dehydrogenase Deficiency, the most common inborn error of faty acid oxidation, has been related to Sudden Infant Death Syndrome”

 

“Defects in the oxidation of Very Long Chain Fatty Acids, is the main metabolic defect found in  Zellweger Syndrome and X-linked adrenoleukodistrophy.”

 

“When following a Fat free diet, it is important to supplement with Liposolubles vitamins and essential fatty acids”

 

“Vegetable oils are rich in Omega6 fatty acids, while fish oils are rich in Omega3”

 

 

 

Some examples of biological interest:

 

Omega 3

Alphalinolenic acid (from the biological point of view, it is also essential) alphalinoleic acid, essential

 

 

Omega6

Linoleic acid  

Linoleic acid 

 

Omega 9

                 Oleic acid (non essential)

 

Oleic acid

 

 

 

Three-dimensional representation of Fatty acids of different groups:

 

tridimensional representation of fatty acids

 

 

More information about Fatty acids:

 

Very good review in Wikipedia

 

The Medical Biochemistry page/lipids/fatty acids

 

Fatty acids in Cyberlipid.org

Answer to L-01


Answer: (a) 

Phosphatidyl choline or Lecithin is a phosphoglyceride, ester of a diacylglycerol with a phosphate linked to another alcohol. The phosphoglyceride group includes, among others, phosphatidyl choline, phosphatidyl serine, phosphatidyl ethanolamine, and phospathidyl inositol.   

Phosphoglycerides and sphingomyelin form the group of phospholipids. Phospholipids are amphipatic molecules: they have a hydrophobic part and a hydrophilic part.  It makes them very suitable for the structure of membranes and lipoproteins.

 Amphipatic molecules have surfactant properties: they decrease surface tension.

Normal lung functions depend on a constant supply of surfactants. Since in the case of a sphere, surface tension is inversely proportional to its radius (Laplace Law), the decrease of the radius of the alveolus during expiration increases the surface tension.

 In absence of a surfactant substance, small alveolus will collapse easily, and the newborn should make great efforts to continue breathing. It explains that some premature babies who show a deficiency of Pulmonary Surfactant develop Respiratory Distress Syndrome (RDS).  

Phospatidyl choline is the most abundant of the phospholipids in the extracellular fluid layer that lines alveoli of normal lungs, and is the main responsible of decreasing the surface tension of the fluid layer of the lung (surfactant properties), preventing atelectasia at the end of the expiration phase of breathing. 

Different lecithins (phosphatidyl cholines) are remodeled by enzymes in pneumocytes in such a way that the resultant product is dipalmitoyl phosphatidyl choline.

Dipalmitoylphosphatidylcholine  

Dipalmitoyl phosphatidyl choline is the most abundant phospholipid in adult surfactant. 

Composition of adult surfactant

         Lipids: 80-90 % by weight

              Phospholipids (80-90 % of the lipids)

            •         Dipalmitoyl-phosphatidylcholine (about 50 %)

                     Phosphatidyl glycerol (about 10 %)

                     Sphingomyelin (about 3 %)

                     Other lipids (10-20 %)

         Surfactant Proteins: 10-20 % by weight 

Once produced in the pneumocyte, surfactant migrates as “lamellar bodies” from the nucleus to the apical cell surface where the surfactant is released by exocytosis into the alveolus.

lamellar bodies exocytosis

Usually between 32 and 36 weeks of pregnancy occurs a notable increase in the synthesis of phosphatidyl choline, while the synthesis of sphingomyelin does not experiment significant changes. That is why the ratio L/S (Lecithine/Sphingmyelin) in amniotic fluid is used as a marker of lung maturation when this information becomes necessary, for example, in the schedule of a medical elective cesarean section.  Since the volume of amniotic fluid is very variable, it makes sense, for eliminating the influence of the dilution factor, to use the ratio of L/S instead of measuring just Lecithin concentration. 

About 30 000 infants present Respiratory Distress Syndrome (former called Hyaline Membrane), in the United States each year. Around 10 % of them die.

Corticosteroid treatment is used to increase lung maturity in cases of risk of premature delivery. The effects of corticosteroids in enhancing the production of surfactant have been related to the induction of palmitate synthase expression in the pneumocytes. It makes more palmitate available for the synthesis a remodeling of lecithins to dipalmitoyl phosphatidyl choline.

The treatment of premature babies with RDS includes the administration of surfactant substances into the tracheobronchial tree. During this process, the infant is turned from side to side to facilitate uniform acinar distribution of surfactant throughout both lungs. Natural and synthetic surfactant preparations have currently been approved by the U.S. Food and Drug Administration, including colfosceril palmitate, a synthetic formulation, and natural surfactants composed of modified bovine and porcine lung extracts. 

More information about surfactants and RDS can be found in:

Feng, A.; Stelle, D: Pediatrics, Respiratory Distress Syndrome

Pramanik, A: Respiratory Distress Syndrome