FATTY ACIDS: STRUCTURE, TYPES, FUNCTIONS, BIOSYNTHESIS - BIOLOGY - 2024

The fatty acids are organic macromolecules derived from hydrocarbons, which are composed of long chains of carbon atoms and hydrogen having hydrophobicity (are liposoluble) and are the structural basis of fats and lipids.

They are very diverse molecules that are distinguished from each other by the length of their hydrocarbon chains and the presence, number, position and / or configuration of their double bonds.

General scheme of a saturated fatty acid (Source: Laghi.l via Wikimedia Commons)

In the lipids of animals, plants, fungi, and microorganisms such as bacteria and yeast, more than 100 different classes of fatty acids have been described and are considered to be species and tissue specific in most living things.

The oils and fats that man consumes daily, whether they are of animal or vegetable origin, are mainly composed of fatty acids.

Introduction

Butter, among other things, is essentially made up of fatty acids (Source: Africa Studio, via pixabay.com)

Fatty acid molecules perform important functions at the cellular level, making them essential components and, since some of them cannot be synthesized by animals, they must obtain them from the diet.

Fatty acids are uncommon as free species in the cell cytosol, so they are generally found as part of other molecular conjugates such as:

- Lipids, in biological membranes.

- Triglycerides or fatty acid esters, which serve as a reserve in plants and animals.

- Waxes, which are solid esters of long-chain fatty acids and alcohols.

- Other similar substances.

In animals, fatty acids are stored in the cytoplasm of cells as small fat droplets made up of a complex called triacylglycerol, which is nothing more than a glycerol molecule to which it has bound, in each of its atoms of carbon, a fatty acid chain by ester linkages.

While bacteria possess short and usually monounsaturated fatty acids, in nature it is common to find fatty acids whose chains have even numbers of carbon atoms, usually between 14 and 24, saturated, monounsaturated or polyunsaturated.

Structure

Fatty acids are amphipathic molecules, that is, they have two chemically defined regions: a hydrophilic polar region and a hydrophobic apolar region.

The hydrophobic region is made up of a long hydrocarbon chain that, in chemical terms, is not very reactive. The hydrophilic region, on the other hand, is composed of a terminal carboxyl group (-COOH), which behaves like an acid.

This terminal carboxyl group or carboxylic acid ionizes in solution, is highly reactive (chemically speaking) and is very hydrophilic, thus representing a covalent binding site between the fatty acid and other molecules.

The length of the hydrocarbon chains of fatty acids usually has even numbers of carbon atoms, and this is closely related to the biosynthetic process by which they are produced, since their growth occurs in pairs of carbons.

The most common fatty acids have chains of between 16 and 18 carbon atoms and in animals, these chains are unbranched.

Classification

Fatty acids are classified into two large groups according to the nature of the bonds that compose them, that is, according to the presence of single bonds or double bonds between the carbon atoms of their hydrocarbon chains.

Thus, there are saturated and unsaturated fatty acids.

- Saturated fatty acids have only single carbon - carbon bonds and all their carbon atoms are "saturated" or attached to hydrogen molecules.

- Unsaturated fatty acids have one or more carbon-carbon double bonds and not all of these are attached to a hydrogen atom.

Unsaturated fatty acids are also divided according to the number of unsaturations (double bonds) into monounsaturated, those with only one double bond, and polyunsaturated, those with more than one.

Saturated fatty acids

They usually have between 4 and 26 carbon atoms linked by single bonds. Its melting point is directly proportional to the length of the chain, that is, to its molecular weight.

Fatty acids that have between 4 and 8 carbons are liquid at 25 ° C and are those that make up edible oils, while those with more than 10 carbon atoms are solid.

Among the most common is lauric acid, which is abundant in palm kernel and coconut oils; palmitic acid, found in palm, cocoa, and lard; and stearic acid, found in cocoa and hydrogenated oils.

They are fatty acids with much more stability than unsaturated fatty acids, especially against oxidation, at least under physiological conditions.

Because the carbon-carbon single bonds can rotate freely, saturated fatty acids are very flexible molecules, although steric hindrance makes the fully extended structure the most energetically stable.

Unsaturated fatty acids

These fatty acids are highly reactive and prone to saturation and oxidation. They are common in plants and marine organisms. Those with only one double bond are known as monounsaturated or monoenoic, while those with more than two are known as polyenoic or polyunsaturated.

The presence of double bonds is common between the carbon atoms between positions 9 and 10, but this does not mean that monounsaturated fatty acids with an unsaturation in another position are not found.

Unlike saturated ones, unsaturated fatty acids are listed not from the terminal carboxyl group, but according to the position of the first C - C double bond. Thus, they are divided into two groups, omega-6 or ω6 acids. and omega-3 or ω3.

Omega-6 acids have the first double bond at carbon number 6 and omega-3 acids have it at carbon number 3. The name ω is given by the double bond closest to the final methyl group.

Double bonds can also be found in two geometric configurations known as "cis" and "trans".

Most of the natural unsaturated fatty acids have a "cis" configuration and the double bonds of the fatty acids present in commercial (hydrogenated) fats are in "trans".

In polyunsaturated fatty acids, two double bonds are usually separated from each other by at least one methyl group, that is, a carbon atom bonded to two hydrogen atoms.

Features

Fatty acids have multiple functions in living organisms and, as mentioned above, one of their essential functions is as an essential part of lipids, which are the main components of biological membranes and one of the three most abundant biomolecules in organisms. alive in conjunction with proteins and carbohydrates.

They are also excellent energy substrates thanks to which large amounts of energy are obtained in the form of ATP and other intermediate metabolites.

Given that animals, for example, are not capable of storing carbohydrates, fatty acids represent the main source of energy storage that comes from the oxidation of sugars consumed in excess.

Short-chain saturated fatty acids in the colon participate in stimulating the absorption of water and sodium, chloride, and bicarbonate ions; In addition, they have functions in the production of mucus, in the proliferation of colonocytes (colon cells), etc.

Unsaturated fatty acids are especially abundant in edible vegetable oils, which are important in the diet of all human beings.

The oils we consume daily are fatty acids (Source: stevepb, via pixabay.com)

Others participate as ligands of some proteins with enzymatic activities, which is why they are important with respect to their effects on the energy metabolism of the cells where they are found.

Biosynthesis

The degradation of fatty acids is known as β-oxidation and occurs in the mitochondria of eukaryotic cells. Biosynthesis, on the contrary, occurs in the cytosol of animal cells and in the chloroplasts (photosynthetic organelles) of plant cells.

It is a process dependent on acetyl-CoA, malonyl-CoA and NADPH, it occurs in all living organisms and in "higher" animals such as mammals. For example, it is very important in liver and fat tissues, as well as in the mammary glands.

The NADPH used for this route is the product, mainly, of the NADP-dependent oxidation reactions of the pentose phosphate route, while acetyl-CoA can come from different sources, for example, from the oxidative decarboxylation of pyruvate, Krebs cycle and the β-oxidation of fatty acids.

The biosynthesis pathway, like that of β-oxidation, is highly regulated in all cells by allosteric effectors and covalent modifications of enzymes that participate in regulation.

-Malonyl-coA synthesis

The pathway begins with the formation of a metabolic intermediate known as malonyl-CoA from an acetyl-CoA molecule and is catalyzed by a multifunctional enzyme called acetyl-CoA carboxylase.

This reaction is an addition reaction of a biotin-dependent carboxyl molecule (-COOH, carboxylation) and occurs in two steps:

1. First, the ATP-dependent transfer of a bicarbonate-derived carboxyl (HCO3-) to a biotin molecule occurs as a prosthetic (non-protein) group associated with acetyl-CoA carboxylase.
2. Subsequently, the CO2 is transferred to acetyl-coA and malonyl-coA is produced.

-Reactions of the route

In animals, the formation of carbohydrate chains of fatty acids occurs further through sequential condensation reactions catalyzed by a multimeric and multifunctional enzyme known as fatty acid synthase.

This enzyme catalyzes the condensation of an acetyl-CoA unit and multiple malonyl-CoA molecules that are produced from the acetyl-CoA carboxylase reaction, a process during which one molecule of CO2 is released for each malonyl-CoA that it adds.

The growing fatty acids are esterified to a protein called "acyl carrier protein" or ACP, which forms thioesters with acyl groups. In E. coli this protein is a 10 kDa polypeptide, but in animals it is part of the fatty acid synthase complex.

The breaking of these thioester bonds releases large amounts of energy, which makes possible, thermodynamically speaking, the occurrence of condensation steps in the biosynthetic pathway.

Fatty acid synthase complex

In bacteria, the fatty acid synthase activity actually corresponds to six independent enzymes that use acetyl-coA and malonyl-coA to form the fatty acids and with which six different enzyme activities are associated.

Homodimeric and multifunctional fatty acid synthase complex from animals (Source: Boehringer Ingelheim via Wikimedia Commons)

In mammals, on the contrary, fatty acid synthase is a multifunctional homodimeric enzyme complex of around 500 kDa molecular weight, which has six different catalytic activities and with which the acyl carrier protein associates.

Step 1: priming reaction

The thiol groups in the cysteine ​​residues responsible for the binding of metabolic intermediates to the ACP enzyme must be loaded, before the beginning of synthesis, with the necessary acyl groups.

To do this, the acetyl group of acetyl-coA is transferred to the thiol group (-SH) of one of the cysteine ​​residues of the ACP subunit of fatty acid synthase. This reaction is catalyzed by the ACP-acyl-transferase subunit.

The acetyl group is then transferred from the ACP to another cysteine ​​residue at the catalytic site of another enzyme subunit of the complex known as β-ketoacyl-ACP-synthase. Thus, the enzyme complex is "primed" to begin synthesis.

Step 2: Transfer of malonyl-CoA units

Malonyl-CoA that is produced by acetyl-CoA carboxylase is transferred to the thiol group in ACP and during this reaction the CoA portion is lost. The reaction is catalyzed by the malonyl-ACP-transferase subunit of the fatty acid synthase complex, which then produces malonyl-ACP.

During this process, the malonyl group is linked to ACP and β-ketoacyl-ACP-synthase through an ester and another sulfhydryl bond, respectively.

Step 3: Condensation

The enzyme β-ketoacyl-ACP-synthase catalyzes the transfer of the acetyl group that was attached to it in the "priming" step to the 2-carbon of the malonyl group that, in the previous step, was transferred to the ACP.

During this reaction, a CO2 molecule is released from malonyl, which corresponds to the CO2 provided by bicarbonate in the acetyl-CoA carboxylase carboxylation reaction. Acetoacetyl-ACP is then produced.

Step 4: Reduction

The β-ketoacyl-ACP-reductase subunit catalyzes the NADPH-dependent reduction of acetoacetyl-ACP, thereby forming D-β-hydroxybutyryl-ACP.

Step 5: dehydration

In this step, trans-α, β-acyl-ACP or ∆2-unsaturated-acyl-ACP (cratonyl-ACP) is formed, a product of the dehydration of D-β-hydroxybutyryl-ACP by the action of the enoyl-subunit. ACP-hydratase.

Later, cratonyl-ACP is reduced to butyryl-ACP by a NADPH-dependent reaction catalyzed by the enoyl-ACP-reductase subunit. This reaction completes the first of seven cycles that are needed to produce palmitoyl-ACP, which is a precursor of almost all fatty acids.

How do the subsequent condensation reactions proceed?

The butyryl group is transferred from ACP to the thiol group of a cysteine ​​residue in β-ketoacyl-ACP-synthase, whereby ACP is able to accept another malonyl group from malonyl-CoA.

In this way, the reaction that occurs is the condensation of malonyl-ACP with buturyl-β-ketoacyl-ACP-synthase, which gives rise to β-ketohexanoyl-ACP + CO2.

The palmitoyl-ACP that arises from the subsequent steps (after the addition of 5 more malonyl units) can be released as free palmitic acid thanks to the activity of the thioesterase enzyme, it can be transferred to CoA or incorporated into phosphatidic acid for phospholipid and triacylglyceride synthesis pathway.

Structure of palmitic acid (Source: Andel, via Wikimedia Commons)

The fatty acid synthase of most organisms stops in the synthesis of palmitoyl-ACP, since the catalytic site of the β-ketoacyl-ACP-synthase subunit has a configuration in which only fatty acids of that length can be accommodated.

How are fatty acids with odd numbers of carbon atoms formed?

These are relatively common in marine organisms and are also synthesized by a fatty acid synthase complex. However, the "priming" reaction occurs with a longer molecule, propionyl-ACP, with three carbon atoms.

Where and how are the longer chain fatty acids formed?

Palmitic acid, as discussed, serves as a precursor for many longer chain saturated and unsaturated fatty acids. The process of "elongation" of fatty acids occurs in the mitochondria, while the introduction of unsaturations occurs essentially in the endoplasmic reticulum.

Many organisms convert their saturated to unsaturated fatty acids as an adaptation to low environmental temperatures, since this allows them to keep the melting point of lipids below room temperature.

Properties of fatty acids

Many of the properties of fatty acids depend on their chain length and the presence and number of unsaturations:

- Unsaturated fatty acids have lower melting points than saturated fatty acids of the same length.

- The length of fatty acids (the number of carbon atoms) is inversely proportional to the fluidity or flexibility of the molecule, that is, the "shorter" molecules are more fluid and vice versa.

In general, fluid fatty substances are composed of short-chain fatty acids with the presence of unsaturations.

Plants have abundant amounts of unsaturated fatty acids, as well as animals that live at very low temperatures, since these, as components of the lipids present in cell membranes, give them greater fluidity under these conditions.

Under physiological conditions, the presence of a double bond in the hydrocarbon chain of a fatty acid causes a curvature of about 30 °, which causes these molecules to occupy a greater space and decrease the strength of their van der Waals interactions.

The presence of double bonds in the fatty acids associated with lipid molecules has direct effects on the degree of "packaging" that they may have in the membranes to which they belong and thus also have effects on membrane proteins.

Example of the formation of a fatty acid micelle with the carboxylic groups exposed towards the aqueous medium (Source: Benutzer: Anderl via Wikimedia Commons)

The solubility of fatty acids decreases as their chain length increases, so they are inversely proportional. In aqueous and lipid mixtures, fatty acids associate in structures known as micelles.

A micelle is a structure in which the aliphatic chains of fatty acids are "enclosed", thus "expelling" all the water molecules and on whose surface the carboxyl groups are found.

Nomenclature

The nomenclature of fatty acids can be somewhat complex, especially if one refers to the common names that they receive, which are often related to some physicochemical property, with the place where they are found or other characteristics.

Many authors consider that since these molecules are ionized at physiological pH thanks to the terminal carboxyl group, one should refer to them as "carboxylates" using the termination "ato" for this.

According to the IUPAC system, the enumeration of the carbon atoms of a fatty acid is made from the carboxyl group at the polar end of the molecule and the first two carbon atoms attached to this group are called α and β, respectively.. The terminal methyl of the chain contains the carbon atom ω.

In general, in the systematic nomenclature they are given the name of the “parental” hydrocarbon (the hydrocarbon with the same number of carbon atoms) and its ending “o” is replaced by “oico”, if it is a fatty acid unsaturated, the ending "enoic" is added.

Consider, for example, the case of a C18 (C18) fatty acid:

- Since the hydrocarbon with the same number of carbon atoms is known as octadecane, the saturated acid is called "octadecanoic acid" or "octadecanoate" and its common name is stearic acid.

- If it has a double bond between a pair of carbon atoms in its structure, it is known as "octadecenoic acid"

- If it has two double bonds c - c, then it is called "octadecadienoic acid" and if it has three "octadecatrienoic acid".

If you want to summarize the nomenclature, then 18: 0 is used for the 18-carbon fatty acid and no double bonds (saturated) and, depending on the degree of unsaturation, then instead of zero, 18: 1 is written for a molecule with a unsaturation, 18: 2 for one with two unsaturations and so on.

If you want to specify between which carbon atoms are the double bonds in unsaturated fatty acids, the symbol ∆ is used with a numerical superscript that indicates the place of unsaturation and the prefix "cis" or "trans", depending on the configuration of this.

References

1. Badui, S. (2006). Food chemistry. (E. Quintanar, Ed.) (4th ed.). Mexico DF: Pearson Education.
2. Garrett, R., & Grisham, C. (2010). Biochemistry (4th ed.). Boston, USA: Brooks / Cole. CENGAGE Learning.
3. Mathews, C., van Holde, K., & Ahern, K. (2000). Biochemistry (3rd ed.). San Francisco, California: Pearson.
4. Murray, R., Bender, D., Botham, K., Kennelly, P., Rodwell, V., & Weil, P. (2009). Harper's Illustrated Biochemistry (28th ed.). McGraw-Hill Medical.
5. Nelson, DL, & Cox, MM (2009). Lehninger Principles of Biochemistry. Omega Editions (5th ed.).
6. Rawn, JD (1998). Biochemistry. Burlington, Massachusetts: Neil Patterson Publishers.
7. Tvrzicka, E., Kremmyda, L., Stankova, B., & Zak, A. (2011). Fatty acids as Biocompounds: Their Role in Human Metabolism, Health and Disease- A Review. Part 1: Classification, Dietary Sources and Biological Functions. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 155 (2), 117–130.