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ASSIGNMENT OF MICROBIOLOGY

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SYNTHESIS OF NUCLEOTIDES, AMINO ACIDS,


LIPIDS, PORPHYRINS, PROTEINS,
POLYSACCHARIDES AND PEPTIDOGLYCAN

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SUBMITTED TO: MADAM MAHRUKH GILANI


SUBMITTED BY: ROOSHANA SADAQAT
ROLL NO. : 2022138024
DEPARTMENT OF ZOOLOGY
SEMESTER-VII
SESSION: 2020-2024
DATE OF SUBMISSION: 23-10-2023

___________________________________________________________________________

GOVERNMENT GRADUATE COLLEGE FOR


WOMEN GULBERG, LAHORE.
TABLE OF CONTENTS

Sr. No. Topics Pg. No.


1 Synthesis of nucleotides 03

1.1 De Novo synthesis 03

1.2 Salvage pathway 03

1.3 Regulation of nucleotide synthesis 03

1.4 Conclusion 04

2 Synthesis of amino acid 04

2.1 De Novo synthesis 04

2.2 Transaminatoin 04

2.3 Synthesis of essential amino acids 04

2.4 Synthesis of non-essential amino acids 04

2.5 Regulation of amino acid synthesis 05

2.6 Conclusion 05

3 Synthesis of Lipids 05

3.1 De Novo synthesis of lipids 05

3.2 Salvage pathway 05

3.3 Synthesis of triglycerides 05

3.4 Synthesis of phospholipids 06

3.5 Synthesis of cholesterol 06

3.6 Regulation of lipid synthesis 06

4 Synthesis of porphyrin 06

4.1 Chemical synthesis of porphyrin 06

4.2 Biological synthesis of porphyrin 06

5 Synthesis of polysaccharides 07

6 Synthesis of peptidoglycan 07

7 Regulation of polysaccharide and peptidoglycan synthesis 08

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1. Synthesis of Nucleotides:
Nucleotides are the building blocks of nucleic acids, which include DNA and RNA. They are
essential for all life, as they play a vital role I n storing and transmitting genetic information.
Nucleotides can be synthesized either de novo (from scratch) or through salvage pathways (by
recycling existing nucleotides) (Peter,1972).

1.1. De Novo Synthesis of Nucleotides:


De novo synthesis of nucleotides is a complex process that occurs in several steps. The first
step is the synthesis of the pentose sugar ribose-5-phosphate. This is followed by the addition
of a nitrogenous base to form a nucleoside. Finally, a phosphate group is added to form the
nucleotide Reichard (Peter,1972).The synthesis of ribose-5-phosphate begins with the
glycolytic intermediate glyceraldehyde 3-phosphate.
A series of enzymatic reactions then convert glyceraldehyde 3-phosphate into ribose-5-
phosphate (Peter,1972).The addition of a nitrogenous base to ribose-5-phosphate is catalyzed
by a family of enzymes called nucleoside diphosphate kinases. There are four different types
of nitrogenous bases found in nucleotides: adenine (A), guanine (G), cytosine (C), and thymine
(T). The type of nitrogenous base added to ribose-5-phosphate determines the type of
nucleotide that is formed (Prescott, et al. (1965). The final step in de novo nucleotide synthesis
is the addition of a phosphate group to the nucleoside. This reaction is catalyzed by the enzyme
nucleoside monophosphate kinase (Prescott, et al. (1965).

1.2. Salvage Pathways:


Salvage pathways are used to recycle existing nucleotides. This is a more energy-efficient
process than de novo synthesis. There are salvage pathways for each of the four types of
nucleotides (Fox, et al. (1981).The salvage pathway for adenine and guanine begins with the
dephosphorylation of the nucleotide to form nucleoside. The nucleoside is then converted to
the free base by the enzyme nucleoside deaminase. The free base can then be reused to
synthesize a new nucleotide (Fox, et al. (1981).The salvage pathway for cytosine and thymine
begins with the deamination of the nucleotide to form uridine monophosphate (UMP). UMP
can then be converted to either CMP or TMP by the addition of an amino group or methyl
group, respectively (Fox, et al. (1981).

1.3. Regulation of Nucleotide Synthesis:


The synthesis of nucleotides is tightly regulated to ensure that there is a sufficient supply of
nucleotides to meet the needs of the cell. The regulation of nucleotide synthesis occurs at
multiple levels, including transcription, translation, and allosteric regulation (Fox, et al. (1981).
1.3.1. Transcriptional regulation: The genes that encode the enzymes involved in
nucleotide synthesis are regulated by a number of transcription factors. These
transcription factors respond to a variety of signals, including the availability of
nucleotides, amino acids, and energy (Anderson, 1990).
1.3.2. Translational regulation: The translation of the mRNAs that encode the enzymes
involved in nucleotide synthesis is also regulated. This regulation is mediated by a
number of microRNAs and other regulatory proteins (Anderson, 1990).

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1.3.3. Allosteric regulation: Many of the enzymes involved in nucleotide synthesis are
allosterically regulated. This means that their activity can be modulated by the binding
of other molecules. For example, the enzyme ribonucleotide reductase, which catalyzes
the conversion of ribonucleotides to deoxy ribonucleotides, is inhibited by the presence
of high levels of deoxy ribonucleotides (Anderson, 1990).
1.4. Conclusion:
The synthesis of nucleotides is a complex and tightly regulated process. It is essential for all
life, as nucleotides play a vital role in storing and transmitting genetic information. Nucleotides
can be synthesized either de novo (from scratch) or through salvage pathways (by recycling
existing nucleotides).

2. Synthesis of Amino acids:


The synthesis of amino acids is a complex process that occurs in all living organisms. Amino
acids are the building blocks of proteins, which are essential for all life. There are two main
pathways for the synthesis of amino acids: de novo synthesis and transamination (Nyhan,
1982).

2.1. De novo synthesis:


De novo synthesis is the synthesis of amino acids from scratch. It is a multi-step process that
requires a variety of enzymes and cofactors. The first step in de novo synthesis is the synthesis
of alpha-ketoglutarate, an intermediate in the Krebs cycle. Alpha-ketoglutarate is then
converted to glutamate, which is the precursor to all other amino acids (Nyhan, 1982).

2.2. Transamination:
Transamination is the transfer of an amino group from one amino acid to another. It is a
relatively simple process that is catalyzed by a family of enzymes called transaminases.
Transamination is used to synthesize non-essential amino acids, which are amino acids that can
be synthesized from other amino acids or from other molecules (Nyhan, 1982).

2.3. Synthesis of essential amino acids:


There are nine essential amino acids, which means that they cannot be synthesized by the
human body and must be obtained from the diet. The essential amino acids are histidine,
isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine
(Nyhan, 1982). The synthesis of essential amino acids begins with the uptake of the aminoacid
precursors from the diet. The precursors are then converted to the corresponding amino acids
by a series of enzymatic reactions (Nyhan, 1982).

2.4. Synthesis of non-essential amino acids:


Non-essential amino acids can be synthesized from other amino acids or from other molecules.
Transamination is the most common pathway for the synthesis of non-essential amino acids
(Magasanik, Boris, 1963).

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2.5. Regulation of amino acid synthesis
The synthesis of amino acids is tightly regulated to ensure that there is a sufficient supply of
amino acids to meet the needs of the cell. The regulation of amino acid synthesis occurs at
multiple levels, including transcription, translation, and allosteric regulation (Magasanik,
Boris, 1963).

2.6. Conclusion:
The synthesis of amino acids is a complex and tightly regulated process. It is essential for all
life, as amino acids are the building blocks of proteins. Amino acids can be synthesized either
de novo (from scratch) or through transamination.

3. Synthesis of Lipids:
Lipid synthesis is the process of producing lipids, which are a large and diverse class of
molecules that are essential for all life. Lipids play a variety of roles in the body, including
energy storage, cell signaling, and membrane structure (Voet, 2016).
There are two main pathways for the synthesis of lipids: de novo synthesis and salvage
pathways.

3.1. De novo synthesis:


De novo synthesis is the synthesis of lipids from scratch, starting with simple molecules such
as acetyl-CoA. De novo synthesis occurs in the liver and adipose tissue, and is the main
pathway for the synthesis of triacylglycerols (fats), phospholipids, and cholesterol (Voet,
2016).

3.2. Salvage pathways:


Salvage pathways are used to recycle existing lipids. Salvage pathways are less energy-
intensive than de novo synthesis, and are used to synthesize a variety of lipids, including
phospholipids, sphingolipids, and cholesterol esters (Voet, 2016).

3.3. Synthesis of triacylglycerols:


Triacylglycerols are the main form of energy storage in the body. They are synthesized in the
liver and adipose tissue from fatty acids and glycerol. The first step in the synthesis of
triacylglycerols is the activation of fatty acids to form fatty acyl-CoA esters. This is done by
the enzyme acyl-CoA synthetase. Fatty acyl-CoA esters are then used to synthesize
triacylglycerols by the enzyme glycerol-3-phosphate acyltransferase. This enzyme catalyzes
the transfer of a fatty acyl group from fatty acyl-CoA to glycerol-3-phosphate. The resulting
product is lysophosphatidic acid, which can be converted to triacylglycerols by the addition
of two more fatty acyl groups (Murray, et al. 2018).

3.4. Synthesis of phospholipids:


Phospholipids are the major components of cell membranes. They are synthesized in the
endoplasmic reticulum and Golgi apparatus (Murray, et al. 2018).The first step in the synthesis
of phospholipids is the formation of phosphatidic acid. This is done by the enzyme
diacylglycerol kinase, which catalyzes the transfer of a phosphate group from ATP to

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diacylglycerol (Murray, et al. 2018).Phosphatidic acid can then be converted to different types
of phospholipids by the addition of different head groups. For example, the addition of choline
to phosphatidic acid produces phosphatidylcholine, which is the most abundant phospholipid
in cell membranes (Murray, et al. 2018).

3.5. Synthesis of cholesterol:


Cholesterol is a steroid lipid that is essential for cell membranes and hormone production. It is
synthesized in the liver and other tissues (Murray, et al. 2018). The first step in the synthesis
of cholesterol is the formation of mevalonate from acetyl-CoA. This is a complex process that
involves several enzymes (Murray, et al. 2018). Mevalonate is then converted to cholesterol
through a series of enzymatic reactions (Murray, et al. 2018).

3.6. Regulation of lipid synthesis:


Lipid synthesis is tightly regulated to ensure that there is a sufficient supply of lipids to meet
the needs of the body. The regulation of lipid synthesis occurs at multiple levels, including
transcription, translation, and allosteric regulation (Murray, et al. 2018).

4. Synthesis of Porphyrins:
Porphyrins are a class of organic compounds that are essential for life. They are the building
blocks of chlorophyll, heme, and other important biomolecules. Porphyrins can be synthesized
either chemically or biologically (Stryer, et al. 2017).

4.1. Chemical synthesis of porphyrins


The chemical synthesis of porphyrins is a complex process that involves several steps. The first
step is the synthesis of the pyrrole ring, which is the basic building block of porphyrins. The
pyrrole ring can be synthesized from a variety of different starting materials, such as alpha-
ketoglutarate and glycine (Stryer, et al. 2017). Once the pyrrole ring has been synthesized, it
can be condensed with other pyrrole rings to form a porphyrin. The condensation reaction is
catalyzed by a variety of different acids and bases (Stryer, et al. 2017).
The type of porphyrin that is synthesized depends on the structure of the pyrrole rings and the
conditions of the condensation reaction. For example, the condensation of four pyrrole rings in
the presence of acid produces uroporphyrinogen III, which is a precursor to heme (Stryer, et
al. 2017).

4.2. Biological synthesis of porphyrins:


The biological synthesis of porphyrins is also a complex process that involves several steps.
The first step is the synthesis of delta-aminolevulinic acid (ALA), which is the precursor to all
porphyrins. ALA is synthesized in the cytoplasm of cells from glycine and succinyl-CoA
(Stryer, et al. 2017). ALA is then transported to the mitochondria, where it is converted to
porphobilinogen (PBG) by the enzyme ALA dehydratase. PBG is then condensed to form four-
ring porphyrinogens by the enzyme PBG deaminase (Stryer, et al. 2017).
The four-ring porphyrinogens are then converted to different types of porphyrins by a variety
of different enzymes. For example, the conversion of uroporphyrinogen III to heme is catalyzed
by the enzymes ferrochelatase and coproporphyrinogen oxidase (Stryer, et al. 2017).

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5. Synthesis of Polysaccharides:
Polysaccharides are long chains of sugar molecules that are linked together by glycosidic
bonds. They are essential for life and play a variety of roles, including energy storage, cell
structure, and immunity (Lehninger, et al. (2017). Polysaccharides are synthesized by enzymes
called glycosyltransferases. These enzymes catalyze the transfer of a sugar molecule from a
donor molecule to an acceptor molecule (Lehninger, et al. (2017).
The donor molecule is typically a nucleotide sugar, which is a sugar molecule that has been
activated by the attachment of a phosphate group (Lehninger, et al. (2017). The acceptor
molecule can be another sugar molecule, a protein, or a lipid. The synthesis of polysaccharides
begins with the formation of a glycosidic bond between two sugar molecules.This reaction is
catalyzed by a glycosyltransferase. The resulting product is a disaccharide (Lehninger, et al.
(2017).
Disaccharides can then be extended to form polysaccharides by the addition of more sugar
molecules. This is done by glycosyltransferases that are specific for the type of polysaccharide
that is being synthesized (Lehninger, et al. (2017).
For example, the synthesis of starch begins with the formation of the disaccharide maltose.
Maltose is then extended to form starch by the addition of more glucose molecules. The
glycosyltransferase that catalyzes this reaction is called starch synthase (Lehninger, et al.
(2017).

6. Synthesis of Peptidoglycan:
Peptidoglycan is a complex polysaccharide that is the major component of the bacterial cell
wall. It is essential for the survival of bacteria, as it protects them from osmotic lysis and other
environmental stresses (Lehninger, et al. (2017). Peptidoglycan is synthesized in the cytoplasm
of bacteria and then transported to the cell wall, where it is assembled into a cross-linked
meshwork (Lehninger, et al. (2017).
The synthesis of peptidoglycan begins with the formation of the precursor molecule UDP-N-
acetylmuramic acid (UDP-MurNAc). UDP-MurNAc is a nucleotide sugar that is synthesized
from glucose-1-phosphate and N-acetylglutamic acid (Lehninger, et al. (2017). UDP-MurNAc
is then used to synthesize peptidoglycan monomers. These monomers are made up of two sugar
molecules, N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc), and a
peptide chain (Lehninger, et al. (2017).
Peptidoglycan monomers are transported to the cell wall by a protein called bactoprenol.
Bactoprenol is a lipid carrier that is embedded in the cell membrane (Lehninger, et al.
(2017). Once peptidoglycan monomers have been transported to the cell wall, they are
assembled into a cross-linked meshwork by a variety of different enzymes (Lehninger, et al.
(2017). These enzymes include transglycosylases, which catalyze the formation of glycosidic
bonds between peptidoglycan monomers, and transpeptidases, which catalyze the formation of
cross-links between peptidoglycan monomers (Lehninger, et al. (2017).

6.1. Regulation of Polysaccharide and Peptidoglycan Synthesis:


The synthesis of polysaccharides and peptidoglycan is tightly regulated to ensure that these
molecules are produced in the correct amounts. The regulation of polysaccharide and
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peptidoglycan synthesis occurs at multiple levels, including transcription, translation, and
allosteric regulation (Lehninger, et al. (2017).

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References:
 Reichard, Peter. (1972) . "Enzymes involved in the de novo synthesis of purine
nucleotides." Annual review of biochemistry 41.1: 73-98.
 Prescott, David M., and John D. Buchanan. (1965). "Biosynthesis of the pyrimidine
nucleotides." Journal of Biological Chemistry 240.10: 3952-3959.
 Fox, Michael S., and David M. Prescott. (1981)."The salvage pathways of purine and
pyrimidine nucleotides." Annual review of biochemistry 50.1: 757-781.
 Anderson, Peter. (1990) . "The salvage pathways of AMP and GMP." Advances in
enzymology and related areas of molecular biology 58: 1-37.
 Nyhan, William L. (1982). "The regulation of pyrimidine biosynthesis in mammals."
Advances in enzymology and related areas of molecular biology 53 : 1-48.
 Magasanik, Boris.( 1963). "Regulation of purine metabolism." In The enzymes, vol.
6, pp. 475-506. New York: Academic Press,.
 Voet, Donald, and Judith G. Voet.( 2016). Biochemistry. 5th ed. W.H. Freeman.
 Murray, Robert K., et al.( 2018). Harper's illustrated biochemistry. 33rd ed. McGraw-
Hill Education.
 Lehninger, Albert L., et al. (2017). Principles of biochemistry. 7th ed. W.H. Freeman.
 Stryer, Lubert, et al. (2017). Biochemistry. 9th ed. W.H. Freeman. Chapters 19 and
20.
 Voet, Donald, and Judith G. Voet.( 2016). Biochemistry. 5th ed. W.H.
Freeman.Chapters 17 and 18. Stryer, Lubert, et al. Biochemistry. 9th ed. W.H.
Freeman, 2017. Chapters 21 and 23.
 Voet, Donald, and Judith G. Voet.( 2016). Biochemistry. 5th ed. W.H.
Freeman.Chapters 19 and 21.
 Murray, Robert K., et al.( 2018). Harper's illustrated biochemistry. 33rd ed. McGraw-
Hill Education. 2018. Chapters 26 and 27.
 Lehninger, Albert L., et al. (2017). Principles of biochemistry. 7th ed. W.H. Freeman,
Chapters 21 and 22.
 Murray, Robert K., et al.( 2018). Harper's illustrated biochemistry. 33rd ed. McGraw-
Hill Education. Chapters 25 and 26.
 Lehninger, Albert L., et al. (2017). Principles of biochemistry. 7th ed. W.H. Freeman,
Chapters 20 and 21.

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