Nucleotide Biosynthesis - 2017

Marcos Alcocer
Nucleotide Biosynthesis – Lectures Marcos Alcocer
Marcos Alcocer
School of Biosciences
University of Nottingham
Main learning objectives Marcos Alcocer
Functions
Nomenclature
Energy
Purines de novo synthesis
Purines salvage synthesis
Pyrimidines de novo synthesis
Biosynthetic regulation
Degradation -
Clinical applications
Main text for references: Stryer et al. - Biochemistry

Overview
Where do they come from? Marcos Alcocer
de novo:
Aspartate
Glycine
CO2
Aspartate
Methenyl Glutamine
tetrahydrofolate
Methenyl Aspartate
Tetrahydrofolate
Glutamine
Overview
de novo Synthesis of Purines Marcos Alcocer
AMP
GMP
Overview
Clinical applications Marcos Alcocer
Dementia
Can be caused by problems in the synthesis of the neurotransmitter
Serotonin. This can be due to:
• Tryptophan is precursor of nicotinate and serotonin
• Endocrine tumour that consumes large amount of tryptophan
• lack of tryptophan in the diet (pellagra)
OH
ATP PPi Gln Glu
Nicotinate (Vit B3, niacin)

Ribonucleotide
Overview
Marcos Alcocer
Overview
Marcos Alcocer
Uric acid crystals can deposit in tiny fluid-filled sacs (bursae) around the joints. These urate crystals
can incite inflammation in the bursae leading to pain and swelling around the joints, a condition called
bursitis. In rare instances, gout leads to a more chronic type of joint inflammation which mimics
rheumatoid arthritis. In chronic (tophaceous) gout, nodular masses of uric acid crystals (tophi) deposit
in different soft tissue areas of the body. Even though they are most commonly found as hard nodules
around the fingers, at the tips of the elbows, and around the big toe, tophi nodules can appear
anywhere in the body. They have been reported in unexpected areas such as in the ears, vocal cords, or
(rarely) around the spinal cord!
Overview
Lesch-Nyhan syndrome
• Problems in the nucleotide syntheses can lead to accumulation of intermediarie

• Children with L-N syndrome begin to bite their finger and lips and will
chew them off if unrestrained. They also will be very aggressive towards
others. Elevate levels of urate will lead to the formation of kidney stones
early in life. It is a sex-linked recessive disorder.
HGPRT
(Hypoxanthine-guanine
Salvage pathway: phosphoribosyl transferase)
Guanine + PRPP  Guanylate + PPi

Hypoxanthine + PRPP  Inosinate + PPi
Overproduction Urate
Overview
Anticancer drugs
• Rapid dividing cells require abundant supply of thymidylate for DNA synthesis
• Inhibitors of TMP synthesis such as Fluorouracil, aminopterin and
methotrexate are largely employed. Trimethoprim has high affinity for
bacteria and protozoa.
Overview
Selection pathways - MAb
“Long life” X
Malignant cells
HGPRT- or
TK- Cell A
+ HAT X
(Hypoxanthine
Thymidine
Aminopterin)
Cell Death !!!
Nucleotide Biosynthesis Marcos Alcocer
Precursors of RNA and DNA, Currency of energy, Activators of biosynthesis

• Functions:
Signal transduction pathways, Activators of Biosynthesis, components of co-enzymes
Nucleotide - Functions Marcos Alcocer
Activated precursors of DNA and RNA
Universal currency of energy (ATP, GTP, NAD)
Activated intermediates in many biosynthesis (UDP-glucose,

CDP-diacylglycerol)
Essential components of signal-transduction pathway
(cAMP, cGMP second messengers within and between cells,
ATP =donnor of phosphoryl groups by kinases)
Components of major coenzymes (NAD, FAD, CoA)
http://highered.mheducation.com/sites/0072507470/student_view0/chapter25/animation__how_the_nad__works.html

• Functions: Signal transduction pathways, Activators of Biosynthesis, components of co-enzymes
• Nomenclature: Adenine, Adenosine, Adenylate or adenosine triphosphate

Nomenclature Marcos Alcocer
Guanine
Purines
Adenine
Cytosine
Pyrimidines
Uracyl
Thymine
Nitrogenous base alone:
Adenine
Guanine
Cytosine
Uracil
Thymine
Nucleoside=
Nitrogenous base + a sugar:
Adenosine
Guanosine
Uridine
Cytidine
The 5’ hydroxy=
Esterification
Nomenclature The 2’ = deoxy… Marcos Alcocer
Nucleotides=
Nitrogenous base + sugar + phosphate ester:
Adenylate (ATP) or adenosine 5’ -triphosphate

Guanylate (GTP)
Urydylate (UTP)
Cytidylate (CTP)

• Energy: Chemical, Transport, mechanical…

http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter25/ani
mation__electron_transport_system_and_atp_synthesis__quiz_1_.html
Marcos Alcocer
ENERGY !!!!
http://www.sumanasinc.com/webcontent/a
nimations/content/electrontransport.html
Why energy??? Marcos Alcocer
Chemical energy –
For synthesis of complex biological molecules.
“to make more of themselves”.
Transport –
Cells often live in dilute environments. They need to expend
energy to transport that nutrient into the cell.
Mechanical Energy –
Cells may be able to change their physical location. All cells need to
move structures (DNA replication, wound repair etc…) within them.
https://www.youtube.com/watch?v=wJyUtbn0O5Y
Marcos Alcocer
Marcos Alcocer

• Biosynthesis of purines: De novo: Components, intermediaries…

Where do they come from?
Regulation
Salvage reactions
Biosynthesis Marcos Alcocer
 Nucleotides are some of the largest monomers that have to be made

by the cell and understandably their synthesis involves many steps and
large amounts of energy.
 Biosynthesis of nucleotides is under tight regulatory control in the cell.

Organisms need to make just the right amount of each base; if too much is
made, energy is wasted, if too little, DNA replication and cellular
metabolism come to a halt. Also, the cell is sensitive to the presence of any
pre-made nucleotides in its environment and will down regulate their de
novo synthesis pathways in favour of using what is already present in the
surroundings.
 Bacteria are capable of interconverting purines (adenine and guanine) and
interconverting pyrimidines (thymidine, cytidine and uracil). Therefore if a
growth medium provides a purine and a pyrimidine, many microbes are
capable of synthesizing the other needed nucleotides from them.
http://lecturer.ukdw.ac.id/dhira/Metabolism/nucleotidesyn.html
Synthesis of Purines (1950, Buchanan et al.) Marcos Alcocer
- Glycine +
de novo - Aspartate +
- Glutamine +
- Tetrahydrofolate +
- CO2 +
- PRPP = Nucleotide
Salvage Ribose phosphate + purine = Nucleotide

de novo Synthesis of PRPP Marcos Alcocer
All nucleotides contain a ribose sugar and phosphate that form the
backbone of DNA and RNA. These are synthesized from ribose 5-
phosphate, a central metabolite of the pentose phosphate pathway. In
this single step reaction, two of the phosphates of ATP are transferred
to ribose 5-phosphate to form 5-phospho-a-D-ribosyl 1-pyrophosphate
(PRPP). This intermediate is required for the biosynthesis of purines,
pyrimidines, NAD, histidine and tryptophan. It plays a critical role in
anabolism.
• Purine synthesis starts by the

addition of an ammonia from
glutamine to PRPP.
• In six more step the five

membered ring of purines in
synthesized with a net cost of
five ATP.
• Glycine, tetrahydrofolate (a one carbon

carrier that donates a methyl group),
glutamine, and bicarbonate (HCO3-) all
donate parts of the five membered ring.
• The final product being 5'-phosphoribosyl-5-

aminoimidazole-4-carbonate (CAIR).
de novo Synthesis of Purines – IMP intermediary Marcos Alcocer
In the next series of reactions the 6 membered ring of purine is

added to CAIR creating Inosine 5'-monophosphate (IMP). This
costs an additional ATP with the members of the ring coming
from aspartate and tetrahydrofolate.
de novo Synthesis of Purines–AMP from IMP Marcos Alcocer
In the synthesis of adenosine monophosphate (AMP), IMP first combines

with aspartate and in a second reaction the combination is split into
fumarate and AMP. The cost to the cell is one GTP. It is interesting to
note that synthesis of ATP from IMP requires GTP as an energy source
and not ATP.
de novo Synthesis of Purines–GMP from IMP Marcos Alcocer
Synthesis or guanine or adenine involves the addition of an extra amino

group. To form guanine monophosphate (GMP), IMP is first oxidized to
xanthosine monophosphate. This adds a ketone group (see figure) that is
attacked by the ammonia on glutamine in the next reaction yielding GMP.
The cost to the cell is one ATP.
R ATP ADP R O
| || || NH3
C=O C - O – P – O-
| | |
R’ R’ O-
R O
R | ||
|| 2HN - C - O – P – O-
C – NH2 | |
| R’ O-
R’
Pi
A carbonyl oxygen atom is replaced by an amino group, i.e., the activated

phosphoryl ester is nucleophilically attacked by an amine with expulsion
of inorganic phosphate. These are common mechanistic theme.


Regulation
Where do they come from? Marcos Alcocer
de novo biosynthesis of purines

Aspartate
Glycine
CO2
Aspartate
Methenyl
tetrahydrofolate
Methenyl
Tetrahydrofolate
Glutamine
PU = GA
AMP
GMP
Synthesis of Purines (1950, Buchanan et al.) Marcos Alcocer
- Glycine +
de novo - Aspartate +
- Glutamine +
= Nucleotide
- Tetrahydrofolate +
- CO2 +
- PRPP
(-)
(-)
Adenylo-
Ribose Phosphoribosyl succinate
AMP
PRPP IMP
5-phosphate amine
Xanthylate GMP
(-) (-)
(-)
Where do purines come from? Marcos Alcocer
de novo biosynthesis
Salvage reactions
“Purine nucleotides can be synthesized from the preformed
bases by a salvage reaction which is simpler and much less
energy costly”
Purine PPi
Purine


Regulation
Salvage reactions
-------------------------------------


Regulation
Salvage reactions
-------------------------------------
• Biosynthesis of De novo: Components, intermediaries…
pyrimidines: Regulation
Biosynthesis Marcos Alcocer
Nucleotides are some of the largest monomers that have to be made by

the cell and understandably their synthesis involves many steps and large
amounts of energy.
Biosynthesis of nucleotides is under tight regulatory control in the cell.

Organisms need to make just the right amount of each base; if too much is
made, energy is wasted, if too little, DNA replication and cellular metabolism
come to a halt. Also, the cell is sensitive to the presence of any pre-made
nucleotides in its environment and will down regulate their de novo synthesis
pathways in favour of using what is already present in the surroundings.
Bacteria are capable of interconverting purines (adenine and guanine) and

interconverting pyrimidines (thymidine, cytidine and uracil). Therefore if a
growth medium provides a purine and a pyrimidine, many microbes are capable
of synthesizing the other needed nucleotides from them.
de novo Synthesis of Pyrimidines Marcos Alcocer
• The synthesis of pyrimidines begins

by combining glutamine, 2 ATP and
bicarbonate to form glutamate, 2 ADP
and carbamoylphosphate.
• Aspartate next reacts with carbamoyl

phosphate forming carbamoylasparate.
• In the critical third step,

carbamoyl asparate is cyclized to
form the recognizable 6 membered
ring of pyrimidines.
Ring is synthesized FIRST!!!!
• The synthesis of pyrimidines begins

by combining glutamine, 2 ATP and
bicarbonate to form glutamate, 2 ADP
and carbamoylphosphate.
• Aspartate next reacts with carbamoyl

phosphate forming carbamoylasparate.
• In the critical third step, carbamoyl asparate is cyclized

to form the recognizable 6 membered ring of pyrimidines.
Ring is synthesized FIRST!!!!

• Later PRPP is combined with the six membered ring to form orotidine 5'-
phosphate. Removal of CO2 results in the formation of Uridine
monophosphate (UMP).
• An addition of an amino group to UTP results in the formation of CTP. The

synthesis of UTP uses 4 ATP (not counting the formation of PRPP) and making
CTP adds an extra ATP to the cost.
• Later PRPP is combined with the six

membered ring to form orotidine 5'-
phosphate. Removal of CO2 results in
the formation of Uradine
monophosphate (UMP). Two kinase
reactions (addition of phosphate)
finally form UTP.
• An addition of an amino group to

UTP results in the formation of CTP.
The synthesis of UTP uses 4 ATP
(not counting the formation of PRPP)
and making CTP adds an extra ATP
to the cost.
Where do pyrimidines come from? Marcos Alcocer
de novo biosynthesis of pyrimidines
Glutamine
+ Bicarbonate
Aspartate
How are Pyrimidine biosynthesis regulated? Marcos Alcocer
dTMP from dUMP Marcos Alcocer
Several well-defined blocking steps Marcos Alcocer


Regulation
Salvage reactions
-------------------------------------
• Degradation: Pyrimidines: DNA/RNA to TCA cycle
Purines: Urea
Synthesis of NAD, FAD, CoA etc…
Where do pyrimidines go ?
Degradation of pyrimidines Marcos Alcocer
Thymine
Dihydrothymine
N-Carbamoylisobutyrate
Aminoisobutyrate
Methyl malonyl CoA
TCA cycle
Where do pyrimidines go?
Marcos Alcocer
Synthesis of nucleotides
Synthesis of deoxynucleotides
Pyrimidines
Degradation -> TCA cycle

In contrast, purines go to:
Marcos Alcocer
Purines
Synthesis of FAD
Synthesis of CoA
Synthesis of NAD
Synthesis of NADP
Degradation, Urea????? …In some species

Where do purines go?
Synthesis of deoxynucleotides Marcos Alcocer
H+ H2O
NADPH NADP+
H
Deoxy
Glutathione
Thioredoxin
NADPH
ADP dADP
adenosine 5’ -diphosphate deoxyadenosine 5’ -diphosphate

Synthesis of FAD Marcos Alcocer
Riboflavin + ATP Riboflavin 5’-phosphate + ADP
Riboflavin 5’-phosphate + ATP Flavin adenine dinucleotide + PPi

FAD
Synthesis of NAD and NADP Marcos Alcocer
OH
ATP PPi Gln Glu

Ribonucleotide
“NADP is derived from NAD by phosphorylation of the 2’

hydroxy group of the adenine ribose moiety (by NAD+ kinase)”
Purines go to:
Marcos Alcocer
Purines
Synthesis of FAD
Synthesis of CoA
Synthesis of NAD
Synthesis of NADP
Degradation, Urea????? …In some species

Where do purines go? SCID=Severe combined
Degradation of purines Immunodeficiency (bubble boy)
Marcos Alcocer
Adenylate deaminase Nucleoside phosphorylase
Allopurinol
Xanthine oxidase (Mo)
“In humans urate is the final product of purine degradation and is

Excreted in the urine.” A drug called allopurinol is given to prevent patients developing complications,
including gout or kidney failure, as a result of the amount of uric acid released when tumour cells are
killed and protein from them is broken down. Allopurinol is normally started at diagnosis and continued
until most leukaemia has been eliminated.
Degradation of purines Marcos Alcocer
Adenylate deaminase Nucleoside phosphorylase
“Urate are highly effective scavenger of reactive oxygen species

May contribute to longer life span and lowering incidence of cancer.”
Is this a lost of function
for the higher organisms
or a gain of function for
Degradation of purines
small invertebrates? Marcos Alcocer
Allantoinase
(Teleost fish)
Uricase
(Mammals
Non primates) Allantoicase
(Amphibians
Fish)
Urease
(Marine invertebrates)
“Birds and reptile excrete a

paste of uric acid to conserve
water.”
How are biosynthesis regulated? Marcos Alcocer
Ribose – 5 Phosphate
PRPP
Phosphoribosyl amine
IMP
Adenylo Xanthylate
succinate
dTTP
AMP GMP


Regulation
Salvage reactions
-------------------------------------
Purines: Urea
• Clinical applications: Pellagra, Gout, anti-Cancer drugs, Leisch Nyhan syndrome, MAb…
Dementia
Can be caused by problems in the synthesis of the neurotransmitter
Serotonin. This can be due to:
• Tryptophan is precursor of nicotinate and serotonin
• Endocrine tumour that consumes large amount of tryptophan
• lack of tryptophan in the diet (pellagra)
OH
ATP PPi Gln Glu

Ribonucleotide
Tryptophan to N-formyl-L-kynurenine
N-formyl-L-kynurenine to L-kynurenine Marcos Alcocer
L-kynurenine to 3-hydroxykynurenine
3-hydroxykynurenine to 3-hydroxyanthranilic acid
3-hydroxyanthranilic acid to 2-amino-3-carboxymuconate
2-amino-3-carboxymuconate to Quinolinic acid
Quinolinic acid to nicotinate-D-ribonucleotide
http://dehydrogenase.co.uk/NAD/
ACE2 links amino acid malnutrition to microbial ecology
and intestinal inflammation
•Tatsuo Hashimoto, et al. Nature 487, 477–481 (26 July 2012)
Marcos Alcocer
Marcos Alcocer
Marcos Alcocer
Pellagra, a loathsome skin disease, it was called mal de la rosa and often
mistaken for leprosy. In the United States, pellagra has often been called the
disease of the four D's -- dermatitis, diarrhea, dementia, and death.
Marcos Alcocer
http://www.visibleproductions.com/index.php?page=asset_detail&asset_id=vpl_0696_001
Gout
High serum levels of urate induce gout a disease which salts of

urate crystallize and damage joints and kidney
Low protein diet and Allopurinol, a inhibitor of Xanthine oxydase,

can be used as treatment
Marcos Alcocer
Marcos Alcocer
Uric acid crystals can deposit in tiny fluid-filled sacs (bursae) around the joints. These urate crystals
can incite inflammation in the bursae leading to pain and swelling around the joints, a condition called
bursitis. In rare instances, gout leads to a more chronic type of joint inflammation which mimics
rheumatoid arthritis. In chronic (tophaceous) gout, nodular masses of uric acid crystals (tophi) deposit
in different soft tissue areas of the body. Even though they are most commonly found as hard nodules
around the fingers, at the tips of the elbows, and around the big toe, tophi nodules can appear
anywhere in the body. They have been reported in unexpected areas such as in the ears, vocal cords, or
(rarely) around the spinal cord!
Antioxidant
In humans urate is the final product of purine degradation.

Urate is a powerful antioxidant. Is it the reason we evolved to have
high levels (near saturation) in our blood???
Is this the reason for our long life span compared to lower primates?
Lesch-Nyhan syndrome
• Problems in the nucleotide syntheses can lead to accumulation of intermediarie

• Children with L-N syndrome begin to bite their finger and lips and will
chew them off if unrestrained. They also will be very aggressive towards
others. Elevate levels of urate will lead to the formation of kidney stones
early in life. It is a sex-linked recessive disorder.
HGPRT
(Hypoxanthine-guanine
Salvage pathway: phosphoribosyl transferase)
Guanine + PRPP  Guanylate + PPi

Hypoxanthine + PRPP  Inosinate + PPi
Overproduction Urate
Anticancer drugs
• Rapid dividing cells require abundant supply of thymidylate for DNA synthesis
• Inhibitors of TMP synthesis such as Fluorouracil, aminopterin and
methotrexate are largely employed. Trimethoprim has high affinity for
bacteria and protozoa.
“Long life”
Malignant cells
Cell A
X =
“Short life” (2-3 days)
Ab producing cells “Long life”
Ab producing cells
Cell B
“Long life”
Malignant cells
Cell A

Ab producing cells
Cell B
“Long life”
Malignant cells
Cell A
+ HAT
(Hypoxanthine
Thymidine
Aminopterin)
Salvage pathway
“Long life”
Malignant cells
Cell A
+
HGPRT- or TK- cells

“Long life” X
Malignant cells
HGPRT- or
TK- Cell A
+ HAT X
(Hypoxanthine
Thymidine
Aminopterin)
Cell Death !!!
Marcos Alcocer
Step 1
Select for myeloma mutants “Poison” salvage pathway
Step 2
Fuse My- cell x spleen cells PEG, electro....
Step 3
Block “de novo” force salvage
Spleen cells die Kill myeloma- cells

after 3 days
Hybridomas= cells that are able to
Use salvage and possess long life
span
X “Long life”
Malignant cells
Cell A
X =
X
Ab producing cells “Long life” HGPRG+ or TK+
Ab producing cells
Cell B
Marcos Alcocer
César Milstein (October 8, 1927 – March 24, 2002), an Argentine scientist, was born in Bahia Blanca,
Argentina. He graduated from the University of Buenos Aires and obtained a PhD under Professor Stoppani
(Professor of Biochemistry) in the Medical School on kinetic studies with the enzyme aldehyde
dehydrogenase. In 1958, funded by the British Council, he joined the Biochemistry Department at the
University of Cambridge to work for a PhD under Malcolm Dixon on the mechanism of metal activation of the
enzyme phosphoglucomutase. During this work he collaborated with Frederick Sanger whose group he joined
with a short-term Medical Research Council appointment.
The major part of Milstein's research career was devoted to studying the structure of antibodies and the
mechanism by which antibody diversity is generated. It was as part of this quest that in 1975 he, together
with Georges Köhler (a postdoctoral fellow in his laboratory), developed the hybridoma technique for the
production of monoclonal antibodies - a discovery recognised by the award of the
1984 Nobel Prize for Physiology or Medicine. This discovery led to an enormous expansion in the exploitation
of antibodies in science and medicine.
Milstein himself made many major contributions to improvements and developments in monoclonal antibody
technology - especially focussing on the use of monoclonal antibodies to provide markers that allow
distinction between different cell types. He also foresaw the potential wealth of ligand-binding reagents
that could result from applying recombinant DNA technology to monoclonal antibodies and inspired the
development of the field of antibody engineering.


Regulation
Salvage reactions
-------------------------------------
Purines: Urea
• Clinical applications: Pellagra, Gout, anti-Cancer drugs, Leisch Nyhan syndrome, MAb…
Main text for references: Stryer et al. - Biochemistry

Nucleotide Biosynthesis - 2017

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Nucleotide Biosynthesis - 2017

Uploaded by

Copyright:

Available Formats

Marcos Alcocer

Nucleotide Biosynthesis – Lectures Marcos Alcocer

Main text for references: Stryer et al. - Biochemistry

Where do they come from? Marcos Alcocer

de novo Synthesis of Purines Marcos Alcocer

Clinical applications Marcos Alcocer

Nicotinate (Vit B3, niacin)

Clinical applications Marcos Alcocer

• Problems in the nucleotide syntheses can lead to accumulation of intermediarie

Guanine + PRPP  Guanylate + PPi

Clinical applications Marcos Alcocer

Clinical applications Marcos Alcocer

Selection pathways - MAb

Precursors of RNA and DNA, Currency of energy, Activators of biosynthesis

Activated precursors of DNA and RNA

Universal currency of energy (ATP, GTP, NAD)

Activated intermediates in many biosynthesis (UDP-glucose,

Components of major coenzymes (NAD, FAD, CoA)

Precursors of RNA and DNA, Currency of energy, Activators of biosynthesis

• Nomenclature: Adenine, Adenosine, Adenylate or adenosine triphosphate

Nitrogenous base alone:

Nitrogenous base + a sugar:

Nomenclature The 2’ = deoxy… Marcos Alcocer

Adenylate (ATP) or adenosine 5’ -triphosphate

Precursors of RNA and DNA, Currency of energy, Activators of biosynthesis

• Nomenclature: Adenine, Adenosine, Adenylate or adenosine triphosphate

• Energy: Chemical, Transport, mechanical…

Precursors of RNA and DNA, Currency of energy, Activators of biosynthesis

• Nomenclature: Adenine, Adenosine, Adenylate or adenosine triphosphate

• Energy: Chemical, Transport, mechanical…

• Biosynthesis of purines: De novo: Components, intermediaries…

 Nucleotides are some of the largest monomers that have to be made

 Biosynthesis of nucleotides is under tight regulatory control in the cell.

Salvage Ribose phosphate + purine = Nucleotide

• Purine synthesis starts by the

• In six more step the five

• Glycine, tetrahydrofolate (a one carbon

• The final product being 5'-phosphoribosyl-5-

In the next series of reactions the 6 membered ring of purine is

In the synthesis of adenosine monophosphate (AMP), IMP first combines

Synthesis or guanine or adenine involves the addition of an extra amino

A carbonyl oxygen atom is replaced by an amino group, i.e., the activated

Precursors of RNA and DNA, Currency of energy, Activators of biosynthesis

• Nomenclature: Adenine, Adenosine, Adenylate or adenosine triphosphate

• Energy: Chemical, Transport, mechanical…

• Biosynthesis of purines: De novo: Components, intermediaries…

de novo biosynthesis of purines

Precursors of RNA and DNA, Currency of energy, Activators of biosynthesis

• Nomenclature: Adenine, Adenosine, Adenylate or adenosine triphosphate

• Energy: Chemical, Transport, mechanical…

• Biosynthesis of purines: De novo: Components, intermediaries…

Precursors of RNA and DNA, Currency of energy, Activators of biosynthesis

• Nomenclature: Adenine, Adenosine, Adenylate or adenosine triphosphate

• Energy: Chemical, Transport, mechanical…

• Biosynthesis of purines: De novo: Components, intermediaries…

Nucleotides are some of the largest monomers that have to be made by

Biosynthesis of nucleotides is under tight regulatory control in the cell.

Bacteria are capable of interconverting purines (adenine and guanine) and

• The synthesis of pyrimidines begins

• Aspartate next reacts with carbamoyl

• In the critical third step,

Ring is synthesized FIRST!!!!

• The synthesis of pyrimidines begins