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Biochem 451 Exam 2 > Nucleotide Synthesis > Flashcards

Nucleotide Synthesis Flashcards

1
Q

Nucleotides consist of

A

a) sugar,
b) nitrogenous base
c) phosphate

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2
Q

Nucleosides consist of:

A

a) sugar

b) nitrogenous base

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3
Q

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

A
  • ribose

- deoxyribose

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4
Q

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

A

nucleotide

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5
Q

The 5 nitrogenous bases found in nucleotides include:

say if purine or pyramadine

A

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

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6
Q

These bases are found in both ribonucleotides and deoxyribonucleotides.

A

adenine, guanine, and cytosine

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7
Q

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

A
  • deoxyribonucleotides.
  • DNA
  • thymidine metabolism
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8
Q

Nucleosides containing purines are named by adding:

Thus, nucleosides containing guanine are called:

A
  • “os” before the “ine.”

- guanosine.

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9
Q

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

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

- cytidine, uridine, and thymidine

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10
Q

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

A

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

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11
Q

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

A

nucleoside monophosphates or individual bases.

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12
Q

Monophosphates be rephosphorylated to triphosphates by:

A

kinases in order to reincorporate them into nucleic acids.

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13
Q

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

A
  • phosphate

- phosphate and sugar

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14
Q

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

A

addition of appropriate sugars and/or phosphates

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15
Q

De novo synthesis of nucleotides utilizes very simply precursors:

A

-amino acids, carbamoyl phosphate, and sugars.

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16
Q

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

A

folate derivatives.

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17
Q

In De novo purine biosynthesis a base is assembled:

A

on the sugar

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18
Q

In De novo pyrimidine biosynthesis, the base is made:

A

apart from the sugar and later attached to it.

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19
Q

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

A

ribonucleotides

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20
Q
  • Deoxyribonucleotides are made from:

- Atoms in the ring of pyrimidines come from:

A
  • ribonucleoside diphosphates.

- aspartate and carbamoyl phosphate.

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21
Q

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

A
  • carbamoyl phosphate synthetase
  • channeling
  • enzyme
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22
Q

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

A
  • carboxyphosphate
  • carbamic acid
  • unstable
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23
Q

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

A

aspartate transcarbamoylase (ATCase)

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24
Q

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

A
  • purines and pyrimidines
  • energy
  • ATP
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25
Q

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

A
  • aspartate
  • carbamoyl phoaphate
  • ATP
  • CTP
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26
Q

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

A

UMP.

27
Q

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

A
  • uridine monophosphate kinase
  • nucleoside diphosphokinase (NDPK)
  • CTP
28
Q

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

A
  • kinase
  • diphosphate
  • triphosphates
  • NDPK
29
Q

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

A
  • CTP synthase
  • CTP
  • CTP
  • UTP
30
Q

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

A
  • aspartate
  • glycine
  • glutamine
  • carbon dioxide
  • tetrahydrofolate
31
Q

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

A

PRPP amidotransferase.

32
Q

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

A
  • AMP
  • GMP
  • partly
33
Q

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

A
  • purine
  • slows
  • high
34
Q

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

A

-fumarate

35
Q

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

A
  • inosinic acid (IMP)
  • purine
  • hypoxanthine
  • phosphate
36
Q

IMP can be converted to:

A

AMP or GMP.

37
Q

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.

A
  • GMP
  • ATP
  • AMP
  • GTP
  • balance
38
Q

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

A
  • oxidation
  • aspartic acid
  • amine
  • fumarate
39
Q

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

A

nucleoside diphosphates and nucleoside triphosphates.

40
Q

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 ____.

A
  • AMP kinase
  • GMP kinase
  • diphosphates
  • NDPK
  • triphosphates
41
Q

Deoxyribonucleotides are made starting with:

A

ribonucleotide reductase (RNR)

42
Q

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

A
  • ribonucleoside

- deoxyribonucleoside

43
Q

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

A
  • nucleoside triphosphates

- triphosphates

44
Q

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

A
  • dUDP (using RNR)
  • dUTP (using NDPK)
  • dUMP (using dUTPase)
  • dTMP (using thymidylate synthase)
45
Q

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

A
  • folate
  • methyl group
  • U
46
Q

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.

A
  • neural tube
  • folic acid
  • folic acid
  • diet
47
Q

Substrates of RNR:

A

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

48
Q

Products of RNR

A

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

49
Q

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.

A
  • R1
  • R2
  • two allosteric
  • active site
  • tyrosine radical
50
Q

Two sites that allosterically regulate RNR and what they do:

A
  • 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).
51
Q

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.

A
  • complementary
  • deoxypyrimidine triphosphates
  • inhibit
  • pyriminine diphosphates
  • purine diphosphates
52
Q

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

A
  • deoxypurine triphosphates
  • inhibit
  • pyrimidine diphosphates
53
Q

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.

A
  • catalyzed

- allosteric binding site

54
Q

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

A
  • tetrahydrofolate derivative

- thymidylate synthase

55
Q

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

A
  • dihydrofolate

- tetrahydrolate

56
Q

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 ___.

A
  • dihydrofolate reductase (DHFR)
  • methotrexate
  • aminopterin
57
Q

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

A
  • xanthine
  • xanthine
  • uric acid
  • excretory
58
Q

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

A
  • water soluble
  • gout
  • GOT
  • big toe
59
Q

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.

A
  • antioxidant
  • multiple sclerosis
  • allopurinol
  • xanthine oxidase
60
Q

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

A
  • purine nucleotides

- pyramidines

61
Q

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

A
  • HGPRT
  • guanine
  • adenine
  • IMP and Hypoxanthine
62
Q

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.

A
  • HGPRT
  • PRPP
  • neurologinal
63
Q

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

A
  • adenosine deaminase
  • dATP
  • RNR
  • division

Biochem 451 Exam 2 (6 decks)

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