- Deoxyribonucleotides are made from: - Atoms in the ring of pyrimidines come from:

- ribonucleoside diphosphates. - aspartate and carbamoyl phosphate.

Nucleotide Synthesis Flashcards by Mudra Choudhury

Nucleotides consist of

a) sugar,
b) nitrogenous base
c) phosphate

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Nucleosides consist of:

a) sugar

b) nitrogenous base

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The sugars of nucleosides and nucleotides are either ____ (found in ribonucleotides of RNA) or _____ (found in deoxyribonucleotides of DNA).

ribose

- deoxyribose

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The term nucleoside phosphate is equivalent to a _____ (nucleoside + phosphate + base = nucleotide). This is true whether it is a monophosphate, diphosphate, or triphosphate.

nucleotide

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The 5 nitrogenous bases found in nucleotides include:

say if purine or pyramadine

adenine (purine), guanine (purine), thymine (pyrimidine), cytosine (pyrimidine), and uracil (pyrimidine).

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These bases are found in both ribonucleotides and deoxyribonucleotides.

adenine, guanine, and cytosine

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Thymine is almost always found in:
Uracil is found primarily in ribonucleotides and rarely in ___, but does appear as a deoxyribonucleotide intermediate in _____ ____.

deoxyribonucleotides.
DNA
thymidine metabolism

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Nucleosides containing purines are named by adding:

Thus, nucleosides containing guanine are called:

“os” before the “ine.”

- guanosine.

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Nucleosides containing pyrmidines are named with the suffix:
Thus, the pyrimidine nucleosides are:

“idine” at the end of the name of the base they contain.

- cytidine, uridine, and thymidine

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Nucleotides and nucleosides are made in cells by two general mechanisms:

salvage pathways (use breakdown products of other nucleotides/nucleosides) or de novo pathways (synthesize nucleotides/nucleosides from scratch).

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In salvage pathways, nucleic acids can be broken down to:

nucleoside monophosphates or individual bases.

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Monophosphates be rephosphorylated to triphosphates by:

kinases in order to reincorporate them into nucleic acids.

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Alternatively, nucleoside monophosphates can lose a _____ (becoming nucleosides) or can lose the ____ and the ___ to become a base.

phosphate

- phosphate and sugar

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Bases can either be broken down or reconverted back to nucleoside monophosphate by:

addition of appropriate sugars and/or phosphates

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De novo synthesis of nucleotides utilizes very simply precursors:

-amino acids, carbamoyl phosphate, and sugars.

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In de novo synthesis, activated carbon moieties are donated by:

folate derivatives.

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In De novo purine biosynthesis a base is assembled:

on the sugar

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In De novo pyrimidine biosynthesis, the base is made:

apart from the sugar and later attached to it.

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In de novo synthesis of nucleotides, _____ are synthesized first.

ribonucleotides

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Deoxyribonucleotides are made from:

- Atoms in the ring of pyrimidines come from:

ribonucleoside diphosphates.

- aspartate and carbamoyl phosphate.

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The enzyme ____ ____ ____ has an interesting catalytic strategy involving _____ (I called it tunneling) of the substrates through the ____ as catalysis occurs.

carbamoyl phosphate synthetase
channeling
enzyme

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Channeling is important because some of the intermediates (such as ___ and ____ ___) are very ____ in aqueous solution.

carboxyphosphate
carbamic acid
unstable

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The most important regulatory enzyme for the entire pathway of pyrimidine biosynthesis is:

aspartate transcarbamoylase (ATCase)

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ATCase plays an important role in balancing the amounts of ____ and ____ and also measuring the amount of ____available (via the amount of ___ present).

purines and pyrimidines
energy
ATP

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The ATCase enzyme catalyzes the linkage of ___ to ___ ___ and is allosterically activated by ___ and allosterically inactivated by ___.

- aspartate - carbamoyl phoaphate - ATP - CTP

The first pyrimidine nucleotide made in the de novo pyrimidine pathway is:

UMP.

UMP is phosphorylated to UDP (by ___ ___ ___) and then to UTP (by ___ ____ (__)) before conversion to ___.

- uridine monophosphate kinase - nucleoside diphosphokinase (NDPK) - CTP

Each nucleoside monophosphate has a specific ____ to convert it to the ____, but all diphosphates (purines, pyrimidines, and all deoxyribonucleoside diphosphates) are converted to ____ by ___.

- kinase - diphosphate - triphosphates - NDPK

Conversion of UTP to CTP is catalyzed by the enzyme __ ____ and it is inhibited by ___, thus providing a balance between the amount of ___ and ___.

- CTP synthase - CTP - CTP - UTP

De novo synthesis of purines uses atoms from ____, ____, ____, ____ ____, and ____ derivatives to make the purine ring.

- aspartate - glycine - glutamine - carbon dioxide - tetrahydrofolate

The most important regulatory enzyme for the first part of purine biosynthesis is:

PRPP amidotransferase.

PRPP amidotransferase is inhibited fully by ___ and __, but is only ___ inhibited (is still partly active) when only one of these molecules is present.

- AMP - GMP - partly

PRPP amidotransferase helps to control ___ production and also ___ purine production when one nucleotide gets to be in too ___ of a concentration.

- purine - slows - high

In the process of making IMP, ____ is released, thereby connecting purine biosynthesis to the citric acid cycle.

-fumarate

The first purine-like intermediate in de novo purine biosynthesis is ___ ___ (___), which has the ____-like base ____ linked to ribose (and ribose is linked to ____).

- inosinic acid (IMP) - purine - hypoxanthine - phosphate

IMP can be converted to:

AMP or GMP.

The pathway by which IMP leads to GMP is inhibited by ___ and uses energy from ___, whereas the pathway where IMP is converted to AMP is inhibited by ___ and uses energy from ____. Thus, the critical ____ of these two nucleotides is maintained using this scheme.

- GMP - ATP - AMP - GTP - balance

The pathway to GMP involves ___, whereas the pathway that leads to AMP uses ___ ___ to donate an ___, and _____ is again released.

- oxidation - aspartic acid - amine - fumarate

Nucleoside monophosphates from de novo synthesis can be converted by kinases to:

nucleoside diphosphates and nucleoside triphosphates.

Kinase enzymes include ___ ___ (also called adenylate kinase) and ___ ___ (also called guanylate kinase), which convert nucleoside monophosphates to nucleoside ___, and nucleoside diphosphate kinase (NDP kinase or ___), which converts all nucleoside diphosphates to nucleoside ____.

- AMP kinase - GMP kinase - diphosphates - NDPK - triphosphates

Deoxyribonucleotides are made starting with:

ribonucleotide reductase (RNR)

RNR catalyzes the conversion of ___ diphosphates to ____ diphosphates (for example, ADP to dADP).

- ribonucleoside | - deoxyribonucleoside

RNR works on all of the ribonucleoside diphosphates. NDPK converts all of the nucleoside diphosphates to ___ ___ using energy from other ___.

- nucleoside triphosphates | - triphosphates

Pathway to making thymidine nucleotides(dTTP) = complicated. It goes from UDP to ___ (using ___), then to ___ (using ___) then to ___ ( using ____), then to ___ (using ____ ____).

- dUDP (using RNR) - dUTP (using NDPK) - dUMP (using dUTPase) - dTMP (using thymidylate synthase)

The last reaction of making thymidine requires ___ to put the ___ ___ onto the __ to make it a T.

- folate - methyl group - U

Spina bifida (incomplete closing of the ___ ___ in infants) has been linked to a deficiency of ___ ___ and a 70% reduction in the disease is realized when ___ ___ is supplemented in the mother's ___ during pregnancy.

- neural tube - folic acid - folic acid - diet

Substrates of RNR:

ribonucleoside diphosphates (ADP, GDP, CDP, or UDP)

Products of RNR

deoxyribonucleoside diphosphates (dADP, dGDP, dCDP, or dUDP)

RNR has two pairs of two identical subunits - __ (large subunit) and __ (small subunit). R1 has ___ ___ binding sites and the ___ ___ of the enzyme. R2 forms a ____ ____ necessary for the reaction mechanism of the enzyme.

- R1 - R2 - two allosteric - active site - tyrosine radical

Two sites that allosterically regulate RNR and what they do:

- Specificity site: controls which substrates the enzyme binds and which deoxyribonucleotides are made - activity binding site (controls whether or not enzyme is active - ATP activates, dATP inactivates).

Specificity sites act in a generally _____ fashion. Binding of ___ ___ to the specificity site tends to ___ binding and reduction of ___ ___ at the enzyme's active site. This also stimulates binding and reduction of ____ ____ at the active site.

- complementary - deoxypyrimidine triphosphates - inhibit - pyriminine diphosphates - purine diphosphates

Binding of ___ ___ tends to ___reduction of purine diphosphates and stimulates reduction of ____ ____.

- deoxypurine triphosphates - inhibit - pyrimidine diphosphates

Don't confuse the active site with the activity site. The ACTIVE SITE is where the reaction is catalyzed, whereas the ACTIVITY SITE is the ___ ___ ___ for ATP or dATP.

- catalyzed | - allosteric binding site

The de novo pathway for thymidine synthesis converts dUMP to dTMP, using a ___ ___and the enyzme ___ ___.

- tetrahydrofolate derivative | - thymidylate synthase

In the process of making dTTP, ___ is produced and must be converted back to ___ in order to keep nucleotide synthesis occurring.

- dihydrofolate | - tetrahydrolate

The enzyme involved in the conversion of dihydrofolate to tetrahydrofolate, ___ ___ (___), is a target of anticancer drugs which inhibit the enzyme. An inhibitor of DHFR is ___ or ___.

- dihydrofolate reductase (DHFR) - methotrexate - aminopterin

Breakdown of purines results in production of ___. Oxidation of ___ yields ___ __. This compound serves an ___ role in birds and dalmations (among other organisms).

- xanthine - xanthine - uric acid - excretory

Uric acid is not very ___ ___ and can precipitate out, cause the painful condition known as ___. ___ often strikes in the ___ ___.

- water soluble - gout - GOT - big toe

Uric acid acts as an ____ and may have protective roles against diseases, such as ___ ___. The disease is successfully treated with ___, which acts as a suicide inhibitor of the ___ ___ enzyme.

- antioxidant - multiple sclerosis - allopurinol - xanthine oxidase

Salvage of ___ ____ is important metabolically - perhaps more so than salvage of ____.

- purine nucleotides | - pyramidines

The enzyme ___ is involved in the direct salvage of ___ nucleotides and indirectly involved in salvage of ___ nucleotides through ___ and ___.

- HGPRT - guanine - adenine - IMP and Hypoxanthine

Lesch-Nyhan Syndrome arises from a deficiency of ___, an enzyme involved in catabolism of guanine and adenine bases. In the absence of this enzyme, ___ accumulates and causes ___ problems.

- HGPRT - PRPP - neurologinal

Severe combined immune deficiency arises from a deficiency of ___ ___. In immune cells of patients with this disease, ___ accumulates, shutting off ___ and stopping cell ___.

- adenosine deaminase - dATP - RNR - division