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BIOCHEMISTR
Y
TBIT106L

DIGITAL ASSIGNMENT 2

Submitted By: Ann Angella Siby

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BIOSYNTHESIS OF PURINES AND PYRIMIDINES

Purine metabolism refers to the metabolic pathways to synthesize and break
down purines that are present in many organisms.

Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases

attached to ribose 5-phosphate. Both adenine and guanine are derived from the
nucleotide inosine monophosphate (IMP), which is the first compound in the pathway to
have a completely formed purine ring system.

The synthesis of pyrimidines is a much simpler process compared to that of purines.

Aspartate, glutamine (amide group) and CO2 contribute to atoms in the formation of
pyrimidine ring.

Pyrimidine ring is first synthesized and then attached to ribose 5-phosphate. This is in
contrast to purine nucleotide synthesis where in purine ring is built upon a pre-existing
ribose-5 phosphate.
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Synthesis Pathways

• For both purines and pyrimidines there are two means of synthesis (often regulate one
another)
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– de novo (from basic metabolites)

– salvage (recycle from pre-existing nucleotides)

SALVAGE PATHWAY
A salvage pathway is a pathway in which a biological product is produced from
intermediates in the degradative pathway of its own or a similar substance. The term often
refers to nucleotide salvage in particular, in which nucleotides (purine and pyrimidine) are
synthesized from intermediates in their degradative pathway.

Nucleotide salvage pathways are used to recover bases and nucleosides that are formed

during degradation of RNA and DNA. This is important in some organs because some
tissues cannot undergo de novo synthesis. The salvaged products can then be converted back
into nucleotides. Salvage pathways are targets for drug development, one family being
called antifolates.

Pyrimidines

Uridine phosphorylase or pyrimidine-nucleoside phosphorylase substitutes the anomeric-

carbon-bonded phosphate of ribose 1-phosphate for the free base uracil, forming the
nucleoside uridine. Uridine kinase (aka uridine–cytidine kinase) can then phosphorylate the
5’-carbon of this nucleoside into uridine monophosphate (UMP). UMP/CMP kinase can
phosphorylate UMP into uridine diphosphate, which nucleoside diphosphate kinase can
phosphorylate into uridine triphosphate.

Thymidine phosphorylase or pyrimidine-nucleoside phosphorylase adds 2-deoxy-alpha-D-

ribose 1-phosphate to thymine, with thymine bonding at the anomeric carbon of the
deoxyribose, forming the deoxynucleoside thymidine. Thymidine kinase can then
phosphorylate the 5’-carbon of this compound into thymidine
monophosphate (TMP). Thymidylate kinase can phosphorylate TMP into thymidine
diphosphate, which nucleoside diphosphate kinase can phosphorylate into thymidine
triphosphate.
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The nucleosides cytidine and deoxycytidine can be salvaged along the uracil pathway
by cytidine deaminase, which converts them to uridine and deoxyuridine, respectively.
Alternatively, uridine–cytidine kinase can phosphorylate them into cytidine
monophosphate (CMP) or deoxycytidine monophosphate (dCMP). UMP/CMP kinase can
phosphorylate (d)CMP into cytidine diphosphate or deoxycytidine diphosphate, which
nucleoside diphosphate kinase can phosphorylate into cytidine triphosphate or deoxycytidine
triphosphate.

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Purines

Phosphoribosyltransferases add activated ribose-5-phosphate (Phosphoribosyl

pyrophosphate, PRPP) to bases, creating nucleoside monophosphates. There are two types of
phosphoribosyltransferases: adenine phosphoribosyltransferase (APRT) and hypoxanthine-
guanine phosphoribosyltransferase (HGPRT). HGPRT is an important enzyme in Purine
pathway metabolism and[2] its deficiency is implicated in Lesch–Nyhan syndrome.

The parasite Plasmodium falciparum relies exclusively on the purine salvage pathway for its
purine nucleotide requirements. Thus, enzymes constituting the purine salvage pathway in
the parasite are potential targets for drug discovery. 5´nucleotidases catalyze the hydrolysis
of purine mononucleotides to their respective nucleosides and phosphate. The nucleosides
are taken up in the cell by transporters and are funneled through the salvage pathway. If the
nucleoside is adenosine, it is acted upon by adenosine deaminases to convert it into inosine.
This metabolite, in turn, is acted upon by purine nucleoside phosphorylase and is converted
to hypoxanthine. Hypoxanthine is acted upon by HGXPRT(hypoxanthine guanine
xanthine phosphoribosyl transferase) in the parasite to convert the respective nucleobase
to its nucleotide monophosphate, respectively (i.e., IMP, GMP or XMP). If it is IMP, this is
subsequently acted upon by adenylosuccinate synthase and adenylosuccinate lyase, in a two
step process, to convert it into sAMP and AMP, respectively. On the contrary, IMP can also
be acted upon by IMP dehydrogenase and GMP synthetase to convert it into GMP.

CLASSIFICATION OF LIPIDS
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These organic compounds are nonpolar molecules, which are soluble only in nonpolar
solvents and insoluble in water because water is a polar molecule. In the human body, these
molecules can be synthesized in the liver and are found in oil, butter, whole milk, cheese,
fried foods and also in some red meats.

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Properties of Lipids
Lipids are a family of organic compounds, composed of fats and oils. These molecules yield
high energy and are responsible for different functions within the human body. Listed below
are some important characteristics of Lipids.

1. Lipids are oily or greasy nonpolar molecules, stored in the adipose tissue of the body.

2. Lipids are a heterogeneous group of compounds, mainly composed of hydrocarbon

chains.

3. Lipids are energy-rich organic molecules, which provide energy for different life
processes.

4. Lipids are a class of compounds characterised by their solubility in nonpolar solvents

and insolubility in water.

5. Lipids are significant in biological systems as they form a mechanical barrier dividing
a cell from the external environment known as the cell membrane.

TYPES OF LIPIDS
There are two major types of lipids- simple lipids and complex lipids. Simple lipids are
esters of fatty acids with various alcohols. For eg. fats and waxes. On the contrary, complex
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lipids are esters of fatty acids with groups other than alcohol and fatty acids. For eg.
phospholipids and sphingolipids. Lipids are made up of a glycerol molecule attached to three
fatty acid molecules. Such a lipid is called triglyceride.

Simple Lipids

Esters of fatty acids with various alcohols.

1. Fats: Esters of fatty acids with glycerol. Oils are fats in the liquid state
2. Waxes: Esters of fatty acids with higher molecular weight monohydric alcohols

CHOLESTROL
 Cholesterol is a wax-like substance, found only in animal source foods.  Triglycerides,
LDL, HDL, VLDL are different types of cholesterol found in the blood cells.
 Cholesterol is an important lipid found in the cell membrane. It is a sterol, which
means that cholesterol is a combination of steroid and alcohol. In the human body,
cholesterol is synthesized in the liver.
 These compounds are biosynthesized by all living cells and are essential for the
structural component of the cell membrane.
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 In the cell membrane, the steroid ring structure of cholesterol provides a rigid
hydrophobic structure that helps boost the rigidity of the cell membrane. Without
cholesterol, the cell membrane would be too fluid.
 It is an important component of cell membranes and is also the basis for the synthesis
of other steroids, including the sex hormones estradiol and testosterone, as well as
other steroids such as cortisone and vitamin D.

• For the fat-like cholesterol to travel in the bloodstream, the cholesterol is packaged in
molecules called lipoproteins. These small packages are made of fat (lipid) on the
inside and proteins on the outside. Two of the lipoproteins that carry cholesterol
throughout the body are LDL and HDL. It is important to have healthy levels of both
LDL and HDL.
• Lifestyle can have an impact on cholesterol level, but genetics influence the amount of
cholesterol the liver produces. While some people can control cholesterol with a
healthy diet and exercise, others may need to add a medication to this regime.
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Structure of Cholestrol

Cholesterol is a 27 carbon compound with a unique structure with a hydrocarbon tail, a

central sterol nucleus made of four hydrocarbon rings, and a hydroxyl group. The center
sterol nucleus or ring is a feature of all steroid hormones.

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Functions of cholesterol

Its main function is to maintain the integrity and fluidity of cell membranes and to serve as a
precursor for the synthesis of substances that are vital for the organism including steroid
hormones, bile acids, and vitamin D.

Importance of cholesterol

We need a small amount of blood cholesterol because the body uses it to: build the structure
of cell membranes. make hormones like oestrogen, testosterone and adrenal hormones. help
your metabolism work efficiently, for example, cholesterol is essential for your body to
produce vitamin D.

Complex Lipids

Esters of fatty acids containing groups in addition to alcohol and a fatty acid.
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1. Phospholipids: These are lipids containing, in addition to fatty acids and alcohol, a
phosphoric acid residue. They frequently have nitrogen-containing bases and other
substituents, eg, in glycerophospholipids the alcohol is glycerol and in
sphingophospholipids the alcohol is sphingosine.

Phospholipids, are a class of lipids whose molecule has a hydrophilic "head"

containing a phosphate group and two hydrophobic "tails" derived from fatty acids,
joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids
typically have omega-3 fatty acids EPA and DHA integrated as part of the
phospholipid molecule. The phosphate group can be modified with simple organic
molecules such as choline, ethanolamine or serine.

Phospholipids are a key component of all cell membranes. They can form lipid
bilayers because of their amphiphilic characteristic. In eukaryotes, cell membranes
also contain another class of lipid, sterol, interspersed among the phospholipids. The
combination provides fluidity in two dimensions combined with mechanical strength
against rupture. Purified phospholipids are produced commercially and have found
applications in nanotechnology and materials science.

The first phospholipid identified in 1847 as such in biological tissues was lecithin, or
phosphatidylcholine, in the egg yolk of chickens by the French chemist and
pharmacist Theodore Nicolas Gobley
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Structure of phospholipids

The structure of a phospholipid molecule contains two hydrophobic tails of fatty acids
and one hydrophilic head of phosphate moiety, jointed together by an alcohol or
glycerol molecule. Due to this structural arrangement, PLs form lipid bilayers and are
a key component of all the cell membranes.
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Functions of phospholipids

1. It regulates the permeability of the membrane.

2. It is also involved in the absorption of fat from the intestine.
3. It helps in ETC- Electron Transport Chain in the mitochondria.
4. Phospholipids help by preventing the accumulation of fats in the liver.
5. It plays a major role in the transportation and removal of cholesterol from the cells.
6. It forms the structural components of the cell membrane with the association of
proteins.
7. They act as surfactants in the respiratory system and are also involved in the
coagulation of blood cells.
8. It helps in the synthesis of different lipoproteins, prostacyclins, prostaglandins and
thromboxanes.

Importance of phospholipids
Phospholipids help by preventing the accumulation of fats in the liver. It plays a major
role in the transportation and removal of cholesterol from the cells. It forms the
structural components of the cell membrane with the association of proteins.

2. Glycolipids (glycosphingolipids): Lipids containing a fatty acid, sphingosine and

carbohydrate. Glycolipids are lipids with a carbohydrate attached by a glycosidic
(covalent) bond. Their role is to maintain the stability of the cell membrane and to
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facilitate cellular recognition, which is crucial to the immune response and in the
connections that allow cells to connect to one another to form tissues. Glycolipids are
found on the surface of all eukaryotic cell membranes, where they extend from the
phospholipid bilayer into the extracellular environment.
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Structure of glycolipids
The essential feature of a glycolipid is the presence of a monosaccharide or
oligosaccharide bound to a lipid moiety. The most common lipids in cellular
membranes are glycerolipids and sphingolipids, which have glycerol or a sphingosine
backbones, respectively. Fatty acids are connected to this backbone, so that the lipid as
a whole has a polar head and a non-polar tail. The lipid bilayer of the cell membrane
consists of two layers of lipids, with the inner and outer surfaces of the membrane
made up of the polar head groups, and the inner part of the membrane made up of the
non-polar fatty acid tails.

The saccharides that are attached to the polar head groups on the outside of the cell are
the ligand components of glycolipids, and are likewise polar, allowing them to be
soluble in the aqueous environment surrounding the cell. The lipid and the saccharide
form a glycoconjugate through a glycosidic bond, which is a covalent bond. The
anomeric carbon of the sugar binds to a free hydroxyl group on the lipid backbone.
The structure of these saccharides varies depending on the structure of the molecules
to which they bind.

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Functions of glycolipids
a. Cell–cell interactions
The main function of glycolipids in the body is to serve as recognition sites for cell–
cell interactions. The saccharide of the glycolipid will bind to a specific
complementary carbohydrate or to a lectin (carbohydrate-binding protein), of a
neighboring cell. The interaction of these cell surface markers is the basis of cell
recognitions, and initiates cellular responses that contribute to activities such as
regulation, growth, and apoptosis.

b. Immune responses
An example of how glycolipids function within the body is the interaction between
leukocytes and endothelial cells during inflammation. Selectins, a class of lectins
found on the surface of leukocytes and endothelial cells bind to the carbohydrates
attached to glycolipids to initiate the immune response. This binding causes
leukocytes to leave circulation and congregate near the site of inflammation. This is
the initial binding mechanism, which is followed by the expression of integrins which
form stronger bonds and allow leukocytes to migrate toward the site of inflammation.
Glycolipids are also responsible for other responses, notably the recognition of host
cells by viruses.

c. Blood types
Blood types are an example of how glycolipids on cell membranes mediate cell
interactions with the surrounding environment. The four main human blood types (A,
B, AB, O) are determined by the oligosaccharide attached to a specific glycolipid on
the surface of red blood cells, which acts as an antigen. The unmodified antigen, called
the H antigen, is the characteristic of type O, and is present on red blood cells of all
blood types. Blood type A has an N-acetylgalactosamine added as the main
determining structure, type B has a galactose, and type AB has all three of these
antigens. Antigens which are not present in an individual's blood will cause antibodies
to be produced,
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which will bind to the foreign glycolipids. For this reason, people with blood type AB
can receive transfusions from all blood types (the universal acceptor), and people with
blood type O can act as donors to all blood types (the universal donor)

Importance of glycolipids
1. It provides energy to the cells.
2. It is an essential part of cell membranes.
3. It helps in determining the blood group of an individual.
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4. It acts as receptors at the surface of the red blood cells.
5. It also functions by assisting the immune system by destroying and eliminating the
pathogen from the body.

3. Other complex lipids: Lipids such as sulfolipids and amino lipids. Lipoproteins may
also be placed in this category.

CLASSIFICATION OF FATTY ACIDS

Fatty acids are a type of lipid composed of carbon, hydrogen, and oxygen arranged as
a variable-length linear carbon chain skeleton with an even number of atoms at one
end.

There are fatty acids with 2 to 30 carbon atoms or more, but the most common and
important ones have 12 to 22 carbon atoms and are found in many different animal
and plant fats.:

They are rarely found free in nature and are the primary constituents of:

• Triacylglycerols (or triglycerides);

• Diacylglycerols;
• Monoacylglycerols (the last two families of compounds are often added to
processed foods);
• Phospholipids of cell membranes;
• Sterol esters.

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1. They are classified into three types based on their degree of saturation/unsaturation in
the carbon chain:
• If there is no double bond, the fatty acid is saturated.
• If there is one double bond, the fatty acid is monounsaturated,
• If there are two or more double bonds, the fatty acid is polyunsaturated.

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2. Furthermore, they can be divided into two broad classes based on the presence or
absence of double/triple bonds:
• If there are no double bonds in the carbon chain, it is saturated.
• If there are one or more double bonds in the carbon chain, it is unsaturated.

3. They are classified as follows based on their ability or inability to be synthesised by

animals, and whose deficiency can be reversed by dietary addition:
• Essential fatty acids
• Not essential

4. They can be functionally classified as follows:

• Short-chain fatty acids: up to 6 carbon atoms
• Medium-chain fatty acids: 8 to 12 carbon atoms.
• Long-chain fatty acids: 14 to 18 carbon atoms
• Very long-chain fatty acids: 20 carbon atoms and up.

5. Other fatty acids

• Oxygenated fatty acids- They have hydroxyl, keto, and epoxy groups; ricinoleic acid,
the main fatty acid in castor oil, is an example.
• Cyclic fatty acids- They have a cyclic unit with three, five, or even six carbon atoms,
similar to prostaglandins.

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