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Production
Bile acid synthesis occurs in liver cells which synthesize primary bile acids (cholic
acid and chenodeoxycholic acid in humans) via cytochrome P450-mediated oxidation of
cholesterol in a multi-step process.
Approximately 600 mg of bile salts are synthesized daily to replace bile acids lost in
the feces..
Prior to secreting any of the bile acids (primary or secondary, see below), liver cells
conjugate them with one of two amino acids, glycine or taurine, to form a total of 8
possible conjugated bile acids. These conjugated bile acids are often referred to as bile
salts because of their physiologically-important acid-base properties.
When these bile acids are secreted into the lumen of the intestine, bacterial partial
dehydroxylation and removal of the glycine and taurine groups forms the secondary bile
acids, deoxycholic acid and lithocholic acid. Cholic acid is converted into deoxycholic acid
and chenodeoxycholic acid into lithocholic acid. All four of these bile acids can be taken
back up into the blood stream, return to the liver, and be re-secreted in a process known
as enterohepatic circulation.[2][3]
Functions
1. As amphipathic molecules with hydrophobic and hydrophilic regions, conjugated bile salts
sit at the lipid/water interface and, at the right concentration, form micelles.[9] The added
solubility of conjugated bile salts aids in their function by preventing passive re-absorption
in the small intestine.
2. Bile acid-containing micelles aid lipases to digest lipids and bring them near the
intestinal brush border membrane, which results in fat absorption.[5]
3. Synthesis of bile acids is a major route of cholesterol metabolism in most species other
than humans. The body produces about 800 mg of cholesterol per day and about half of
that is used for bile acid synthesis producing 400–600 mg daily.
4. Human adults secrete between 12-18 g of bile acids into the intestine each day, mostly
after meals. The bile acid pool size is between 4–6 g, which means that bile acids are
recycled several times each day. About 95% of bile acids are reabsorbed by active
transport in the ileum and recycled back to the liver for further secretion into the biliary
system and gallbladder.
5. Bile acids have other functions, including eliminating cholesterol from the body, driving the
flow of bile to eliminate certain catabolites (including bilirubin), emulsifying fat-soluble
vitamins to enable their absorption, and aiding in motility and the reduction of the bacteria
flora found in the small intestine and biliary tract.[4]
Wax
Waxes are a class of chemical compounds that are malleable near ambient temperatures. They are also a
type of lipid. Characteristically, they melt above 45 °C (113 °F) to give a low viscosity liquid. Waxes
are insoluble in water but soluble in organic, nonpolar solvents. All waxes are organic compounds, both
synthetically and naturally occurring.
Plant and animal waxes[edit]
Waxes are synthesized by many plants and animals. Those of animal origin typically consist of wax esters
derived from a variety of carboxylic acids and fatty alcohols. In waxes of plant origin characteristic mixtures
of unesterified hydrocarbons may predominate over esters.[1] The composition depends not only on
species, but also on geographic location of the organism. Because they are mixtures, naturally produced
waxes are softer and melt at lower temperatures than the pure components.[citation needed]
Chemical Structure[edit]
Wax is a type of long chain apolar lipid which made up of various n-alkanes, ketones, primary alcohol,
secondary alcohols, monoesters, beta diketones, aldehydes,etc. Waxes will form protective coating on
plants and fruits, and in animal (example: beewax, whale spermaceti, etc.). More commonly, wax is ester of
alcohol and fatty acids. They differ from fats since they don’t have triglyceride ester of three fatty acids.
Waxes are water resistant, so they are insoluble in water
Animal waxes[edit]
The most commonly known animal wax is beeswax, but other insects secrete waxes. A major component of
the beeswax used in constructing honeycombs is the ester myricyl palmitate which is an ester
of triacontanol and palmitic acid. Its melting point is 62-65 °C.Spermaceti occurs in large amounts in the
head oil of the sperm whale. One of its main constituents is cetyl palmitate, another ester of a fatty acid and
a fatty alcohol. Lanolin is a wax obtained from wool, consisting of esters of sterols.[2]
Plant waxes[edit]
Plants secrete waxes into and on the surface of their cuticles as a way to control evaporation, wettability and
hydration.[3] The epicuticular waxes of plants are mixtures of substituted long-chain aliphatic hydrocarbons,
containing alkanes, alkyl esters, fatty acids, primary and secondary alcohols, diols, ketones,aldehydes.[1] From
the commercial perspective, the most important plant wax is Carnauba wax, a hard wax obtained from the
Brazilian palm Copernicia prunifera. Containing the ester myricyl cerotate, it has many applications, such as
confectionery and other food coatings, car and furniture polish, floss coating,surfboard wax, and other uses.
Other more specialized vegetable waxes include candelilla wax and ouricury wax.
One component of beeswax is myricin (myricyl palmitate, CH3(CH2)14COO(CH2)12CH3). Myricyl palmitate is a saturated
16 carbon fatty acid esterified to a 30 carbon alcohol.
Properties[edit]
Due to the versatility of waxes, nature has manipulated them for their water-resistant properties, colligative
properties (high melting point, relatively low viscosity at high temperatures, transparency, etc.) and coating
properties.
Types of Waxes[edit]
1. Beeswax – for consumption
2. Chinese Wax – for polishes
3. Ear Wax – used as a protective layer over the ear membrane
4. Lanolin – for rust prevention and cosmetics
5. Shellac – used as a wood sealant
6. Spermaceti – for cosmetics and leatherworking
7. Vegetable (many different types extracted from plants) – used as a protective layer on the plant to
prevent loss of water
8. Mineral – used as fine polishes
9. Petroleum – fuels, paints, culinary, candles
10.Synthetic – modified waxes for use in the medical field
Functions and Applications[edit]
Waxes contain many functions in society. Man has manipulated and synthesized many waxes to be used
for cosmetics, sealants and lubricants, insecticides, UV protection, energy reserves, food, etc.
LIPOAMINO ACIDS
Several classes of complex lipids devoid of phosphorus have one amino acid linked to both a long-chain
alcohol and a fatty acid or to a glycerolipid, they are sometimes named lipoamino acids.
Simple forms of these lipoamino acids containing only amino acid and fatty acid(s) are described in the
"simple lipids" part.
They are present exclusively in Bacteria and lower plants (fern, algae, protozoa)
Two groups of complex lipoamino acids are known:
1 - Lipids having an amino acid with N-acyl and/or ester linkages
2 - Lipids having a glycerol and an amino acid with ether linkage
LIPOAMINO ACIDS :
N-ACYL and ESTER DERIVATIVES of AMINO ACIDS
Several types of derivatives are known according to their
amino acid moiety:
1 - Lysine-containing lipids
Some of them are known as Siolipin A. In these
compounds lysine is N-linked to a fatty acid (normal or
hydroxylated, R1) and to a fatty alcohol (R2) (ester link).
They are found in Streptomyces species of bacteria.
2 - Ornithine-containing lipids
In these lipids ornithine is linked to a fatty acid (R1) by an
amide link and to a long-chain fatty alcohol (R2) by an
ester link.
The fatty acid chain (R1) has 16 to 18 carbon atoms and
the fatty alcohol may have a cyclopropane ring. They
occur in photosynthetic purple bacteria (Gorshein A,
Biochim Biophys Acta 1968, 152, 358).
Less complex forms containing ornithine linked to fatty
acids only were also described.
Other ornithine-containing lipids are found in Gram
negative bacteria and have been reported in some Gram-
positives, like Mycobacterium and Streptomyces species
but are absent in Archaea and Eukarya (Geiger O et al.,
Prog Lipid Res 2010, 49, 46). They are commonly formed
of a 3-hydroxy fatty acyl group that is attached in amide
linkage to the a-amino group of ornithine an a second fatty
acyl group is ester-linked to the 3-hydroxy position of the
first fatty acid.
3- Glycine-containing lipids
The glycine-containing lipids have been identified in the
gliding bacterium Cytophaga johnsonae (Kawazoe R et
al., J Bacteriol 199, 173, 5470) and the Gram-negative
sea-water bacterium Cyclobacterium marinus (Batrakov
SG et al., Chem Phys Lipids 1999, 99, 139). These lipids
consist of the amino acid glycine and two fatty acyl
residues, using the acyl-oxyacyl structure. The structure of
glycine lipid from C. marinus is mainly a N-[3-D-(13-
methyltetradecanoyloxy)- 15-methylhexadecanoyl]glycine
(see figure below). In this structure, an iso-3-hydroxyfatty
acyl group is amide-linked to glycine and its 3-hydroxy
group is esterified to another iso-fatty acid.
LIPOAMINO ACIDS WITH ETHER LINKAGE
These lipids are glycerolipids and are mainly derived from homoserine, they are characterics of algae.
Some forms have an alanine moiety instead of homoserine. As the polar head may be considered derived
from betaine (N,N,N-trimethyl glycine), these lipids are commonly named betain lipids.
The homoserine-derived lipids were first
identified in a yellow-green
algae, Ochromonas
danica (Chrysophyceae) where they
account for more than 50% of total
lipids(Brown AE et al., Biochemistry 1974,
13, 3476). It has been suggested that
homoserine-derived lipids, which are
formed by an ether linkage between
homoserine and a diacylglycerol molecule,
are widely distributed and even found in
some higher plants (Rozentsvet OA et al.,
Phytochemistry 2000, 54, 401).
Alanine-derived lipids (diacylglyceryl hydroxymethyltrimethyl-b-alanine) was first identified in Ochromonas
danica (Vogel G et al., Chem Phys lipids 1990, 52, 99) and was shown to replace the homoserine-derived lipids
in brown algae but are absent in the greens (Eichenberger W, Plant Physiol Biochem 1993, 31, 213).
Another betain lipid, diacylglyceryl carboxyhydroxymethylcholine, was then discovered in Pavlova
lutheri (Haptophyceae) (Kato M et al., Phytochemistry 1994, 37, 279).
Lysine-containing diacylglycerol was isolated from Mycobacterium phlei strain IST (Lerouge P et al., Chem
Phys Lipids 1988, 49, 161). Lysine is esterified to 1,2- diglyceride via an ester linkage and the major fatty acyl
substitutions are palmitic and tuberculostearic acid.
Lipoproteins
Lipoproteins are molecules made of proteins and fat.
They carry cholesterol and similar substances through the
blood. A blood test can be done to measure a specific type
oflipoprotein called lipoprotein-a, or Lp(a). A high level
of Lp(a) is considered a risk factor for heart disease
A lipoprotein is a biochemical assembly that contains both proteins and lipids, bound to the
proteins, which allow fats to move through the water inside and outside cells. The proteins serve
to emulsify the lipid molecules. Manyenzymes, transporters, structural
proteins, antigens, adhesins, and toxins are lipoproteins. Examples include theplasma
lipoprotein particles classified under high-density (HDL) and low-density (LDL) lipoproteins,
which enable fats to be carried in the blood stream, the transmembrane proteins of
the mitochondrion and the chloroplast, and bacterial lipoproteins.[1
Classification
Lipoproteins may be classified as follows, listed from larger and less dense to smaller and denser.
Lipoproteins are larger and less dense when the fat to protein ratio is increased. They are classified on
the basis of electrophoresis and ultracentrifugation.
•Chylomicrons carry triglycerides (fat) from the intestines to the liver, to skeletal muscle, and
to adipose tissue.
•Very-low-density lipoproteins (VLDL) carry (newly synthesised) triglycerides from the liver to adipose
tissue.
•Intermediate-density lipoproteins (IDL) are intermediate between VLDL and LDL. They are not usually
detectable in the blood when fasting.
•Low-density lipoproteins (LDL) carry 3,000 to 6,000 fat molecules (phospholipids, cholesterol,
triglycerides, etc.) around the body. LDL particles are sometimes referred to as "bad" lipoprotein
because concentrations, dose related, correlate with atherosclerosis progression.
• large buoyant LDL (lb LDL) particles
• small dense LDL (sd LDL) particles
• Lipoprotein(a) is a lipoprotein particle of a certain phenotype
•High-density lipoproteins (HDL) collect fat molecules (phospholipids, cholesterol, triglycerides, etc.)
from the body's cells/tissues, and take it back to the liver. HDLs are sometimes referred to as "good"
lipoprotein because higher concentrations correlate with low rates of atherosclerosis progression
and/or regression.
Density (g/mL) Class Diameter (nm) % protein % cholesterol%
phospholipid
% triacylglycerol& cholesterol ester
>1.063 HDL 5–15 33 30 29 4
1.019–1.063 LDL 18–28 25 50 21 8
1.006–1.019 IDL 25–50 18 29 22 31
0.95–1.006 VLDL 30–80 10 22 18 50
<0.95 Chylomicrons 100-1000 <2 8 7 84
For young healthy research subjects, ~70 kg, 154 lb, the following applies:
Function
The handling of lipoprotein particles in the
body is referred to as lipoprotein particle
metabolism. It is divided into two
pathways, exogenous and endogenous,
depending in large part on whether the
lipoprotein particles in question are
composed chiefly of dietary (exogenous)
lipids or whether they originated in the liver
(endogenous), through de novo synthesis of
triacylglycerols.
The hepatocytes are the main platform for
the handling of triacylglyerols
and cholesterol; the liver can also store
certain amounts of glycogen and
triacylglycerols. While adipocytes are the
main storage cells for triacylglycerols, they
do not produce any lipoproteins.
Proteolipids
Proteolipids can be defined as all proteins containing
containing covalently bound lipid moieties, including fatty
acids, isoprenoids, cholesterol and
glycosylphosphatidylinositol
During the course of the study of brain sulfatides with Lees MB, Folch J described for the first time in 1951 the
presence of special proteins in rat brain myelin which could be solubilized in organic solvents (chloroform /
methanol / water mixtures) (Folch J et al., J Biol Chem 1951, 191, 807). These substances were named
"proteolipides" and were considered as a novel lipoprotein but quite different from the other known lipoproteins.
These proteolipids were shown to be present mainly in neural tissues but also in heart, kidney, liver, and
muscles but absent from blood plasma.
During thirty years the definition of proteolipids was exclusively used to refer to a family of various proteins
which are related by their solubility in mixtures of chloroform and methanol (Lees MB et al., Biochim Biophys
Acta 1979, 559, 209). Thus, the archetypal proteolipid found initially in myelin is now known as "proteolipid
protein" or PLP.
The presence of fatty acids covalently associated with hydrophobic proteins was first described in Gram-
negative bacteria but rapidly extended to myelin PLP and to the Ca++-dependent ATPase complex of
sarcoplasmic reticulum. These discoveries led to the new definition for proteolipid : a protein that contains a
lipid moiety as part of its primary structure.
Curiously, only two types of acylated proteins have been identified :
- Myristoylated proteins
Myristic acid (C14:0) is bound to the amino-terminal glycine residue (stable amide linkage)
- Palmitoylated proteins
Palmitic acid (C16:0) is bound to side chains of cystein residues (labile thioester linkage). Other
fatty acids can also be present (C16:1, C18:2, C20:0 ..)
MYRISTOYLATED PROTEINS
The first proteins to be demonstrated to contain myristic acid were calcineurin B (Aitken A et al.,
FEBS Lett 1982, 150, 314) and the catalytic subunit of the cyclic AMP-dependent protein kinase
(Carr SA et al., Proc Natl Acad Sci USA 1982, 79, 6128).
It was shown that myristic acid (R2) was attached through an amide linkage to the a-amino group
of glycine (R1) at the N-terminus of both proteins :
R1--NH--CO--R2
Later, a wide range of proteins of viral and cellular origin have been shown to be modified by
acylation with myristic acid (Olson EN, Prog Lipid Res 1988, 27, 177).
Myristoylated proteins are localized to the cytosol or to cellular membranes and sometimes to
both. Membrane-bound myristoylated proteins interact tightly with the bilayer so that drastic
conditions may be used to release them from membranes (Olson EN et al., J Biol Chem 1986,
261, 2458). It is now well established that myristoylation is able to direct soluble proteins to
membranes but the specificity of targeting remains unclear.
The function for myristoylation is also not well known. It was speculated that these proteins may
represent enzymes involved in lipid metabolism or carrier proteins.
PALMITOYLATED PROTEINS
These proteins are the most extensively studied among proteolipids and the first member among them to be identified was the
myelin PLP which represents the major component of the myelin proteins (at least 40%). The long-chain fatty acids (R2, mainly
C16:0, C18:0 and C18:1) constitute about 2-4% of the PLP dry weight and are covalently bound by thioester linkages to cystein
residues (R1).
R1--S--CO--R2
The presence of thioester bonds was demonstrated by in vitro and in vivo acylation (Ross NW et al., J Neurosci Res 1988, 21,
35; Bizzozero OA et al., J Neurochem 1990, 55, 1986).
PLP was shown to be palmitoylated with acyl-CoA by a non-enzymatic mechanism and depalmitoylated by a specific myelin-
associated acyltransferase.
The extreme hydrophobicity of PLP is easily explained by a composition of about 50% apolar amino acid residues and a high
degree of fatty acid acylation (Weimbs T et al., Biochemistry 1992, 31, 12289).
Besides myelin PLP, several other membrane proteins were shown to be S-palmitoylated. The best known examples are the
followings :
- myelin P0 glycoprotein in peripheral nervous system (Bizzozero OA et al., Anal Biochem 1989, 180, 59).
- ligatin in neonatal enterocytes (Jakoi ER et al., J Biol Chem 1987, 262, 1300).
- lung surfactant proteolipid (Stults JT et al., Am J Physiol 1991, 261, L118).
- rhodopsin in retina cells (O'Brien P et al., J Biol Chem 1987, 262, 5210).
- sodium channel polypeptide (Levinson SR et al., Biophys J 1986, 49, 378A).
- P-selectin in vascular endothelium (Fujimoto T et al., J Biol Chem 1993, 268, 11394).
- band 3 protein in erythrocytes (Okudo K et al. J Biol Chem 1991, 266, 16420).
- hepatic asialoglycoprotein receptor (Zeng FY et al., J Biol Chem 1995, 270, 21382).
- glycoprotein proteolipids from Sindbis virus (Schmidt MFG et al., Proc Natl Acad Sci USA 1979, 76, 1687).
More than 20 proteins modified by covalent palmitic acid were reviewed in 1988 (Olson EN, Prog Lipid Res
1988, 27, 177) and 14 were added in 1994 (Bizzozero OA et al., Neurochem Res 1994, 19, 923).
A phylogenetic conservation of fatty acid acylation was demonstrated in studying brain myelin from amphibians,
reptiles, birds and mammals, suggesting a critical role of this post-translational modification for PLP function
(Bizzozero OA et al., Neurochem Res 1999, 24, 269). In all species, PLP contains about 3% (w/w) of bound
fatty acids, 78% of them being C16:0, C16:1, C18:0 and C18:1. Curiously, hydroxy and branched-chain fatty
acids are absent. While discrepancies are found concerning the fatty acid to protein stoichiometry, it is now
accepted that no more than 3 moles of fatty acids are bound to one mole of PLP (MW = 25000). Interestingly,
PLP appears to be strongly associated in situ with acidic phospholipids, mostly phosphatidylserine. It is
estimated that about 15 molecules of phospholipids form a boundary lipid matrix around a molecule of PLP.
Lipopolysaccharide
Lipopolysaccharides (LPS), also known as lipoglycans and endotoxins, are
large molecules consisting of a lipid and apolysaccharide composed of O-antigen, outer
core and inner core joined by a covalent bond; they are found in the outer
membrane of Gram-negative bacteria, and elicit strong immune responses in animals.
The term lipooligosaccharide ("LOS") is used to refer to a low-molecular-weight form of
bacterial lipopolysaccharides.
The toxic activity of LPS was first discovered and termed "endotoxin" by Richard Friedrich Johannes Pfeiffer,
who distinguished between exotoxins, which he classified as a toxin that is released by bacteria into the
surrounding environment, and endotoxins, which he considered to be a toxin kept "within" the bacterial cell
and released only after destruction of the bacterial cell wall.[1]:84 Subsequent work showed that release of
LPS from gram negative microbes does not necessarily require the destruction of the bacterial cell wall, but
rather, LPS is secreted as part of the normal physiological activity of membrane vesicle trafficking in the form
of bacterial outer membrane vesicles (OMVs), which may also contain other virulence factors and proteins.[2]
Today, the term 'endotoxin' is mostly used synonymously with LPS,[3] although there are a few molecules
secreted by other bacteria that are not related to LPS, such as the so-called delta endotoxin proteins
secreted by Bacillus thuringiensis.
Discovery
Functions in bacteria
LPS is the major component of the outer membrane of Gram-negative bacteria, contributing greatly to the
structural integrity of the bacteria, and protecting the membrane from certain kinds of chemical attack. LPS
also increases the negative charge of the cell membrane and helps stabilize the overall membrane structure. It
is of crucial importance to gram-negative bacteria, whose death results if it is mutated or removed. LPS
induces a strong response from normal animal immune systems. It has also been implicated in non-pathogenic
aspects of bacterial ecology, including surface adhesion, bacteriophage sensitivity, and interactions with
predators such as amoebae.
LPS is required for the proper conformation of Omptin activity; however, smooth LPS will sterically hinder
omptins.
Composition
It comprises three parts:
1.O antigen (or O polysaccharide)
2.Core oligosaccharide
3.Lipid A
The saccharolipid Kdo2-Lipid A. Glucosamine residues
in blue, Kdo residues in red, acyl chains in black and
phosphate groups in green.
O-antigen[edit]
A repetitive glycan polymer contained within an LPS is referred to as the O antigen, O polysaccharide, or O side-
chain of the bacteria. The O antigen is attached to the core oligosaccharide, and comprises the outermost domain
of the LPS molecule. The composition of the O chain varies from strain to strain. For example, there are over 160
different O antigen structures produced by different E. coli strains.[4] The presence or absence of O chains
determines whether the LPS is considered rough or smooth. Full-length O-chains would render the LPS smooth,
whereas the absence or reduction of O-chains would make the LPS rough.[5] Bacteria with rough LPS usually have
more penetrable cell membranes to hydrophobic antibiotics, since a rough LPS is more hydrophobic.[6] O antigen
is exposed on the very outer surface of the bacterial cell, and, as a consequence, is a target for recognition by
host antibodies.
Core[edit]
Main article: Core oligosaccharide
The Core domain always contains an oligosaccharide component that attaches directly to lipid A and commonly
contains sugars such as heptose and 3-deoxy-D-mannooctulosonic Acid (also known as KDO, keto-
deoxyoctulosonate).[7] The LPS Cores of many bacteria also contain non-carbohydrate components, such as
phosphate, amino acids, and ethanolamine substituents.
Lipid A[edit]
Main article: Lipid A
Lipid A is, in normal circumstances, a phosphorylated glucosamine disaccharide decorated with multiple fatty
acids. These hydrophobic fatty acid chains anchor the LPS into the bacterial membrane, and the rest of the LPS
projects from the cell surface. The lipid A domain is responsible for much of the toxicity of Gram-negative bacteria.
When bacterial cells are lysed by the immune system, fragments of membrane containing lipid A are released into
the circulation, causing fever, diarrhea, and possible fatal endotoxic shock (also called septic shock). The Lipid A
moiety is a very conserved component of the LPS.[8]
LPS modifications[edit]
The making of LPS can be modified in order to present a specific sugar structure. Those can be
recognised by either other LPS (which enables to inhibit LPS toxins) or glycosyltransferases that use
those sugar structure to add more specific sugars. It has recently been shown that a specific enzyme
in the intestine (alkaline phosphatase) can detoxify LPS by removing the two phosphate groups found
on LPS carbohydrates.[11] This may function as an adaptive mechanism to help the host manage
potentially toxic effects of gram-negative bacteria normally found in the small intestine. A different
enzyme may detoxify LPS when it enters, or is produced in, animal tissues. Neutrophils,
macrophages, and dendritic cells produce a lipase, acyloxyacyl hydrolase (AOAH), that inactivates
LPS by removing the two secondary acyl chains from lipid A. If they are given LPS parenterally, mice
that lack AOAH develop high titers of non-specific antibodies, develop prolonged hepatomegaly, and
experience prolonged endotoxin tolerance. LPS inactivation may be required for animals to restore
homeostasis after parenteral LPS exposure.[12]