Free or unesterified
fatty acids are ubiquitous if minor components of all living tissues. In
animals, much of the dietary lipid is hydrolysed to free acids before it is
absorbed and utilized for lipid synthesis. Intact lipids in tissues can be
hydrolysed to free acids by a variety of lipolytic enzymes (e.g. lipoprotein
lipase, hormone-sensitive lipase, phospholipase A), before being metabolized in
various ways including oxidation, desaturation, elongation or
re-esterification. As free acids can interact with a wide range of enzyme
systems in both specific and non-specific ways, they must be rapidly
sequestered in tissues by various means to ensure that their activities are
closely regulated.
Monomeric
fatty acids in the free state have very low solubilities in aqueous media. In
serum, they are transported between tissues bound to the protein albumin, which
has up to six strong binding sites and a large number of weak binding sites
where non-polar interactions are possible between the fatty acid hydrocarbon
chains and uncharged amino acid side chains. In this way, the concentration of
a long-chain fatty acid in serum can be increased by as much as 500 times above
its normal maximum. However, the bound fatty acids can diffuse into the aqueous
phase, where they are rapidly taken up into the outer leaflet of the plasma
membrane by non-enzymatic mechanisms. It is then possible that fatty acids cross
the membrane simply and rapidly by a biophysical process
There
is also evidence that specific transporter proteins may be involved in part to
activate by formation of acyl-coA prior to further esterification, but also to
ensure vectorial transport so that specific fatty acids are directed towards
particular purposes. Certainly within the cell, a family of fatty acid binding
or transport proteins has essential functions in fatty acid trafficking
pathways and in fatty acid activation, many of which are specific to particular
tissues. These include uptake of dietary lipids in the intestine, targeting of
fatty acids in the liver to either catabolic or anabolic pathways, regulation
of storage in adipose tissue, targeting to β-oxidation pathways in muscle, and maintenance
of phospholipid compositions in neural tissues. It appears that cells have
several overlapping mechanisms that ensure sufficient uptake and directed
intracellular movement of the fatty acids required for their physiological
functions.
Apart
from their obvious role as a source of energy (see our web page on
acylcarnitines, for example), unesterified fatty acids can act as second
messengers required for the translation of external signals, as they can be
produced rapidly as a consequence of the binding of specific agonists to plasma
membrane receptors. In this way, they can substitute for the second messengers
of the inositide pathways. Fatty acids are effective also in operating at
specific intracellular locations reversibly to amplify or otherwise modify
signals. For example, they influence the activities of protein kinases,
phospholipases, G-proteins, adenylate and guanylate cyclases, and many other
metabolic processes. Part of the action of fatty acids may occur indirectly via
metabolism of arachidonic acid to eicosanoids. On the other hand, there is much
evidence that fatty acids per se are messengers that mediate the responses of
the cell to extracellular signals. Many of these reactions are specific to
particular fatty acids. For example, polyunsaturated fatty acids, including
docosahexaenoic and arachidonic acids, bind to the retinoid X receptor and
induce activation. Some related processes appear to occur in plants.
In
addition in animal tissues, long-chain polyunsaturated fatty acids are involved
in regulating gene expression, mainly targeting genes that encode proteins with
roles in fatty acid transport or metabolism. In this respect, (n-3) fatty acids
are more potent than (n-6) fatty acids. Straight-chain saturated and monoenoic
fatty acids do not appear to be involved in the process, but surprisingly
poly-methyl-branched fatty acids, such as phytanic and pristanic, may have a
function of this kind. In some circumstances, both the free acids per se and
their coenzyme A esters may be involved. Fatty acid-binding proteins bind
long-chain fatty acids with high affinity in the cytoplasm and transport them
to nuclei, which they enter via the nuclear pores, where they are able to form
complexes with nuclear receptors enabling them to regulate receptor activation.
Scottish
thistleThe mechanisms by which modulation of gene transcription occurs are only
partially resolved, and this is the subject of considerable research effort,
especially with respect to the family of transcription factors, i.e. peroxisome
proliferator-activated receptors (PPARs), in the nuclei of cells. The effects
can be highly specific, different fatty acids binding to or activating
different types of PPAR, although the PPARα and hepatocyte nuclear factor 4α
(HNF4α) are especially important. In particular, polyunsaturated fatty acids
may exert beneficial effects by up-regulating the expression of genes encoding
enzymes involved in oxidation of fatty acids, while at the same time
down-regulating genes for enzymes involved in lipid synthesis. They also
influence glucose metabolism. As a result, unesterified fatty acids may
mitigate the undesirable symptoms of the metabolic syndrome and may even reduce
the risk of heart disease. In contrast, abnormal PPAR activation can be a
factor in the lipotoxicity observed with obesity, insulin resistance, type 2
diabetes and hyperlipidemia. Abnormally elevated levels of non-esterified fatty
acids in plasma, for example, are associated with the pathologies of these
disease states. Also, they increase greatly the amounts of key bioactive lipids
in tissues such as the pancreas, skeletal muscle and adipose tissue.
However,
some of the mediator effects appear to be independent of PPARs and are
characterized by involvement with cell surface receptors instead. Thus,
multiple G-protein-coupled receptors for free fatty acids have been identified
that function on the cell surface and have important roles in nutrition
regulation. Some of these are activated by short-chain and others by medium-
and long-chain free fatty acids. The former are expressed preferentially in
pancreatic β-cells and mediate insulin secretion. In certain intestinal cells,
there are believed to be such ‘fatty acid sensing molecules’, which recognise
the presence of free long-chain acids in digesta. These stimulate the release
of the hormone cholecystokinin, which in turn causes the gall-bladder to
contract and release bile to aid digestion. In effect, free fatty acids act as
nutrient sensors to regulate energy homeostasis.
Similarly,
in bacteria, it has been demonstrated that the bacterial fatty acid transport
and trafficking system leads to fatty acid-responsive regulation of gene
expression.
Free
fatty acids have potent antimicrobial, antiviral and antifungal properties, and
they exert such effects in some living systems, especially the skin and mucosa
of the lung. As they are powerful detergents and will inhibit very many enzymes
systems in a non-specific manner, it is not clear whether the biocidal
properties are also non-specific. Unsaturated fatty acids seem to have the
greatest effects, but this may be because they can insert more readily into
membranes. At high concentrations in vitro, free fatty acids are known to
perturb membrane structures, but cytotoxic effects come into play before this
can become relevant.
In
chemistry,
and especially in biochemistry,
a fatty acid is a carboxylic
acid with a long aliphatic
tail (chain),
which is either saturated or unsaturated. Most naturally
occurring fatty acids have a chain of an even number of carbon atoms, from 4 to
28.Fatty acids are usually derived from triglycerides
or phospholipids.
When they are not attached to other molecules, they are known as
"free" fatty acids. Fatty acids are important sources of fuel
because, when metabolized, they yield large quantities of ATP. Many cell types can use either glucose
or fatty acids for this purpose. In particular, heart and skeletal muscle
prefer fatty acids. The brain cannot use fatty acids as a source of fuel; it
relies on glucose or ketone bodies
Types of fatty acids
1.
Fatty
acids that have carbon-carbon double bonds are known as unsaturated.
2.
 |
Fatty acids without double bonds are known as saturated. They differ in length as well.
Length of free fatty acid chains
Fatty acid chains differ by length, often categorized as short to very
long.
·
Short-chain fatty acids
(SCFA) are fatty acids with aliphatic
tails of fewer than six carbons (i.e. butyric
acid).
·
Medium-chain fatty acids
(MCFA) are fatty acids with aliphatic
tails of 6–12[3]
carbons,
which can form medium-chain triglycerides.
Three dimensional
representations of several fatty acidsUnsaturated fatty acids
Unsaturated fatty acids have one or more double bonds between carbon atoms. (Pairs of
carbon atoms connected by double bonds can be saturated by adding hydrogen
atoms to them, converting the double bonds to single bonds. Therefore, the
double bonds are called unsaturated.)
The two carbon atoms in the chain that are bound next to
either side of the double bond can occur in a cis or trans configuration.
cis
A cis
configuration means that adjacent hydrogen atoms are on the same side of the
double bond. The rigidity of the double bond freezes its conformation and, in
the case of the cis isomer, causes the chain to bend and restricts the
conformational freedom of the fatty acid. The more double bonds the chain has
in the cis configuration, the less flexibility it has. When a chain has many cis
bonds, it becomes quite curved in its most accessible conformations. For
example, oleic acid, with one double bond, has a "kink" in it,
whereas linoleic acid, with two double bonds, has a more pronounced bend.
Alpha-linolenic acid, with three double bonds, favors a hooked shape. The
effect of this is that, in restricted environments, such as when fatty acids
are part of a phospholipid in a lipid bilayer, or triglycerides in lipid
droplets, cis bonds limit the ability of fatty acids to be closely packed, and
therefore could affect the melting temperature of the membrane or of the fat.
trans
A trans
configuration, by contrast, means that the next two hydrogen atoms are bound to
opposite sides of the double bond. As a result, they do not cause the chain to
bend much, and their shape is similar to straight saturated fatty acids.
In most naturally occurring unsaturated fatty acids, each
double bond has three n carbon atoms after it, for some n, and all are cis
bonds. Most fatty acids in the trans configuration (trans fats) are not found
in nature and are the result of human processing (e.g., hydrogenation).
The differences in geometry between the various types of
unsaturated fatty acids, as well as between saturated and unsaturated fatty
acids, play an important role in biological processes, and in the construction
of biological structures (such as cell membranes).
Examples
of Unsaturated Fatty Acids
Common name
|
Chemical structure
|
CH3(CH2)3CH=CH(CH2)7COOH
|
|
CH3(CH2)5CH=CH(CH2)7COOH
|
|
CH3(CH2)8CH=CH(CH2)4COOH
|
|
CH3(CH2)7CH=CH(CH2)7COOH
|
|
CH3(CH2)7CH=CH(CH2)7COOH
|
|
CH3(CH2)5CH=CH(CH2)9COOH
|
|
CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH
|
|
CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH
|
|
CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7COOH
|
|
CH3CH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH
|
|
CH3(CH2)7CH=CH(CH2)11COOH
|
|
CH3CH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)2COOH
|
Essential fatty acids
Fatty acids that are required by the human
body but cannot be made in sufficient quantity from other substrates, and
therefore must be obtained from food, are called essential fatty acids. There
are two series of essential fatty acids: one has a double bond three carbon
atoms removed from the methyl end; the other has a double bond six carbon atoms
removed from the methyl end. Humans lack the ability to introduce double bonds
in fatty acids beyond carbons 9 and 10, as counted from the carboxylic acid
side. Two essential fatty acids are linoleic acid (LA) and alpha-linolenic acid
(ALA). They are widely distributed in plant oils. The human body has a limited
ability to convert ALA into the longer-chain n-3 fatty acids eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA), which can also be obtained from
fish.
Saturated fatty acids
Saturated fatty acids are long-chain
carboxylic acids that usually have between 12 and 24 carbon atoms and have no
double bonds. Thus, saturated fatty acids are saturated with hydrogen (since
double bonds reduce the number of hydrogens on each carbon). Because saturated
fatty acids have only single bonds, each carbon atom within the chain has 2
hydrogen atoms (except for the omega carbon at the end that has 3 hydrogens).
Arachidic acid, a saturated fatty acid.
Nomenclature
Several
different systems of nomenclature are used for fatty acids. The following table
describes the most common systems.
Numbering of carbon atoms
Production
Fatty acids are usually produced industrially
by the hydrolysis of triglycerides, with the removal of glycerol (see
oleochemicals). Phospholipids represent another source. Some fatty acids are
produced synthetically by hydrocarboxylation of alkenes.
Free fatty acids
The biosynthesis of fatty acids involves the
condensation of acetyl-CoA. Since this coenzyme carries a two-carbon-atom
group, almost all natural fatty acids have even numbers of carbon atoms.
The "uncombined fatty acids" or "free fatty acids"
found in organisms[which?] come from the breakdown of a triglyceride[citation
needed]. Because they are insoluble in water, these fatty acids are transported
(solubilized, circulated) while bound to plasma protein albumin. The levels of
"free fatty acid" in the blood are limited by the availability of
albumin binding sites.
Reactions
of fatty acids
Fatty acids exhibit reactions like other
carboxylic acid, i.e. they undergo esterification and acid-base reactions.
Acidity
Fatty acids do not show a great variation in
their acidities, as indicated by their respective pKa. Nonanoic acid, for
example, has a pKa of 4.96, being only slightly weaker than acetic acid (4.76).
As the chain length increases, the solubility of the fatty acids in water
decreases very rapidly, so that the longer-chain fatty acids have minimal
effect on the pH of an aqueous solution. Even those fatty acids that are
insoluble in water will dissolve in warm ethanol, and can be titrated with
sodium hydroxide solution using phenolphthalein as an indicator to a pale-pink
endpoint. This analysis is used to determine the free fatty acid content of
fats; i.e., the proportion of the triglycerides that have been hydrolyzed.
Hydrogenation
and hardening
Hydrogenation of unsaturated fatty acids is
widely practiced to give saturated fatty acids, which are less prone toward
rancidification. Since the saturated fatty acids are higher melting than the
unsaturated relatives, the process is called hardening. This technology is used
to convert vegetable oils into margarine. During partial hydrogenation,
unsaturated fatty acids can be isomerized from cis to trans configuration.
More forcing hydrogenation, i.e. using higher
pressures of H2 and higher temperatures, converts fatty acids into fatty
alcohols. Fatty alcohols are, however, more easily produced from fatty acid
esters.
In the Varrentrapp reaction certain
unsaturated fatty acids are cleaved in molten alkali, a reaction at one time of
relevance to structure elucidation.
Auto-oxidation
and rancidity
Rancidification
Unsaturated fatty acids undergo a chemical
change known as auto-oxidation. The process requires oxygen (air) and is
accelerated by the presence of trace metals. Vegetable oils resist this process
because they contain antioxidants, such as tocopherol. Fats and oils often are
treated with chelating agents such as citric acid to remove the metal
catalysts.
Ozonolysis
Unsaturated fatty acids are susceptible to
degradation by ozone. This reaction is practiced in the production of azelaic
acid ((CH2)7(CO2H)2) from oleic acid.
Digestion
and intake
Main article: Digestion (Fat
digestion)
Short- and medium-chain fatty acids are
absorbed directly into the blood via intestine capillaries and travel through
the portal vein just as other absorbed nutrients do. However, long-chain fatty
acids are not directly released into the intestinal capillaries. Instead they
are absorbed into the fatty walls of the intestine villi and reassembled again
into triglycerides. The triglycerides are coated with cholesterol and protein
(protein coat) into a compound called a chylomicron.
Within the villi, the chylomicron enters a
lymphatic capillary called a lacteal, which merges into larger lymphatic
vessels. It is transported via the lymphatic system and the thoracic duct up to
a location near the heart (where the arteries and veins are larger). The
thoracic duct empties the chylomicrons into the bloodstream via the left
subclavian vein. At this point the chylomicrons can transport the triglycerides
to tissues where they are stored or metabolized for energy.
Metabolism
Main article: Fatty acid
metabolism
Fatty acids (provided either by ingestion or
by drawing on triglycerides stored in fatty tissues) are distributed to cells
to serve as a fuel for muscular contraction and general metabolism. They are
consumed by mitochondria to produce ATP through beta oxidation.
Distribution
Main article: Blood fatty acids
Blood fatty acids are in different forms in
different stages in the blood circulation. They are taken in through the
intestine in chylomicrons, but also exist in very low density lipoproteins
(VLDL) and low density lipoproteins (LDL) after processing in the liver. In
addition, when released from adipocytes, fatty acids exist in the blood as free
fatty acids.
It is proposed that the blend of fatty acids
exuded by mammalian skin, together with lactic acid and pyruvic acid, is
distinctive and enables animals with a keen sense of smell to differentiate
individuals.
Bibliography
2. Food Standards Agency (1991). "Fats and
Oils". McCance &
Widdowson's the Composition of Foods. Royal Society of Chemistry.
3. Christopher Beermann1, J Jelinek1, T Reinecker2,
A Hauenschild2, G Boehm1, and H-U Klör2,
4.
Webliography
1. http://From
Wikipedia, the free encyclopedia
2. http://
compounds-fatty.html
3. http://
index.htm
4.
FATTY ACIDS
Nazeeb V.P
1 M.sc Food
Processing
PGP College of
Arts & Science
