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]