Nucleotide Metabolism (lec. 34)

The three pyrimidines are _____, ______, & _______.

Cytosine, Uracil, Thiamine ("CUT the PY")

Both DNA & RNA contain the pyrimidine ________, but they differ in their second base.

Cytosine.

In pyrimidine synthesis, the pathway begins with the AA _____, and this species also found in the urea cycle.

D; carbamoyl phosphate

For the synthesis of both purine and pyrimidine, the two AA ____ & ____ are required.

DQ

Sources of the atoms of the pyrimidine ring are ____, ____ & ____.

DQ, CO2

Both APRT and HGPRT use ______ as the source of 5-phosphate group.

PRPP

The de novo purine nucleotide synthesis begins with ______.

PRPP (Phosphoribosyl pyrophosphate)

The committed step in purine nucleotide biosynthesis is ______________.

PRPP amidotransferase.

Purine synthesis is regulated via the first two enzymes _______ and ________ and are inhibited by the _______ _______.

PRPP synthetase and PRPP amidotransferase; purine nucleotides (end products).

_______ is an activated pentose that participates in the synthesis and ________ of _______ and ________.

PRPP; salvage; purines; pyrimidines

Pyrimidines are degraded to H2O soluble products ___ or ___. They are either excreted or oxidized.

beta-A or beta-aminoisobutyrate

For pyrimidine synth. the carbamoyl phosphate (CPS II) is made in the ______.

cytoplasm

Purine synthesis is regulated by _______ inhibition.

feedback

The reactions leading from IMP to AMP & GMP are regulated by _______ inhibition by the end products. In both cases, the inhibition is __________.

feedback; competitive

The conversion IMP to ATP & GMP is __________ by the end products.

inhibited

The difference between T and U is that T has a _____ _____.

methyl group

In the urea cycle, the carbamoyl phosphate is made in the ______.

mitochondria

NDP are synthesize from the corresponding NMP by base-specific __________ _______ _________.

nucleoside monophosphate kinases.

The salvage pathway for purines involves the conversion of purines to _______ ______ and used by the body for energy.

nucleoside triphosphates

The addition of a pentose sugar to a base produces a ________.

nucleoside.

PRPP amidotransferase is inhibited by

purine 5'-nucleotides AMP and GMP (end products).

Both PRPP synthetase and PRPP amidotransferase (first two steps of purine synth.) are inhibited by the ________ _______.

purine nucleotides

If the addition of a sugar to a base is ribose a ________ is produced; and if 2-deoxyribose, _______.

ribonucleoside; deoxyribonucleoside.

Unlike the purine ring, the pyrimidine ring is synthesized BEFORE being attached to ________.

ribose 5-phosphate

The purine base is synthesized on the ______ _______.

ribose moiety (moiety = "portion" or "part")

For tissues that cannot synthesize nucleotides de novo The only source of purine nucleotides is the ______ _______.

salvage pathway

Ribonucleotides include these four:

CTP UTP ATP GTP

The _____ atoms in the rings are numbered with the prime' symbol.

Carbon

PRPP synthetase is activated by _____ and inhibited by _______ _________.

Inorganic phosphate; purine nucleotides (end products)

The reactions of APRT or HGPRT with PRPP are ______ because of the release of pyrophosphate.

Irreversible

De novo synthesis of purines is mots active in the _______, which exports the bases and _________ to other tissues.

Liver; nucleotides (de novo = "afresh" defined: synthesis of complex molecules from simple molecules)

____ is a cofactor in the PRPP synthetase reaction.

Mg 2+

The structure of nucleotide consists of three main components:

Nitrogenous base Pentose monosaccharide Phosphate group(s) 1, 2, or 3

The two enzymes involved in the conversion of purine bases to nucleotides. What are they?

1. APRT 2. HGPRT

The IMP synthesis pathway requires ___ ATP as energy source.

4

The purine is built up style by step beginning with ____________ and two ring closure steps from the purine nucleus.

5-phosphoribosylamine

The synthesis of IMP is __ steps long and contains the base __________

9; hypoxanthine

In the biosynthesis of purine, IMP is converted to either ___ or ___ and is energy-________.

AMP or GMP; dependent

The conversion of IMP to GMP requires hydrolysis of ___ molecule.

ATP

PRPP is synthesized from ______ and _________. The synthesis is catalyzed by _______.

ATP, ribose 5-phosphate; PRPP synthetase.

Both DNA & RNA contain the same purine bases ________ & __________.

Adenine, Guanine ("PURe As Gold")

________ enzyme is particularly active in liver & muscle where ATP energy turnover is high.

Adenylate kinase

The function of _________ enzyme is to maintain equilibrium among ___, ___ & ____.

Adenylate kinase; AMP, ADP, ATP

If both AMP and GMP are present in adequate amounts, the pathway of purine synthesis is turned off at the __________ step

Amidostransferase

In pyrimidine synthesis, the enzymes of the pathway are all cytosolic except for _____________, which is on the outer surface of the ____ _______ ________ .

Dihydroorotate DH; inner mito membrane

What is the type of inhibition is exerted upon the enzymes of purine synthesis by the end products?

Feedback inhibition

In purine synthesis, AA _____ molecule is added to the growing purine precursor.

G

Atoms of purine ring are contributed by a number of compounds including 3 AAs ____, ____, & ____; and the gas ______.

GDQ (Guys Don't Queef); CO2

The conversion of IMP to AMP requires hydrolysis of ____ molecule.

GTP

Xanthine is formed directly from _____ & _____.

Guanine and Hypoxanthine.

___________ is the "parent" purine nucleotide.

IMP (inosine monophosphate)

The inhibition of IMP provides a mechanism for diverting the IMP to the synthesis of the species of _______ present in lesser amounts.

Purines

Where does cytoplasmic CPS obtain it's nitrogen?

Q (the R chain)

The committed step, PRPP amidotransferase, provides the ribose moiety, which reacts with AA ______ to form ____________.

Q; phosphoribosylamine

DNA contains pyrimidine _______, while RNA contains _______.

Thymine; Uracil

Purines are degraded to ____ ____.

Uric Acid

The end product of purine degradation in humans is _______

Uric Acid

The common intermediate in the degradation process of the purines is ________.

Xanthine

The degradation of xanthine, a common intermediate, to uric acid is catalyzed by enzyme ________.

Xanthine oxidase