Lecture 12 (part 1): NT Nomenclature & Purine Synthesis

nucleotide metabolism is connected to ______ and ______ metabolism, but NOT _______ metabolism

amino acid; sugar; lipid

what are the 3 components of nucleotides?

ribose, base, phosphate

which carbons are numbered with a prime (‘)

ribose

which carbon in the ribose sugar is the 1’ carbon? (what is it attached to?

carbon attached to the base

the glycosidic bond attaches the ______ to the _____

ribose sugar; base

what is the bond between the ribose and the phosphate called?

phosphodiester bond

what molecule is this?

nucleoside

what molecule is this?

nucleoside-monophosphate

what molecule is this?

nucleoside-diphosphate

what molecule is this?

nucleoside-triphosphatea

a ribose-base WITHOUT a phosphate is called a ___________, once a phosphate is attached, it is called a _________

nucleoside; nucleotide

which bases are PURINES

adenine and guanine

what bases are PYRIMIDINES

uracil, thymine, cytosine

PYRIMIDINES have ______ ring, and PURINES have _______ ring

1; 2

where is the glycosidic bond on pyrimidines?

bottom nitrogen

where is the glycosidic bond on purines?

HN

how many nitrogens do purines have?

4

how many nitrogens do pyrimidines have?

2

which base is this?

cytosine

which base is this?

thymine

which base is this?

adenine

which base is this?

guanine

which base is this?

uracil

purine rings have a ______ ring structure

heterocyclic

if adenosine is the nucleoSIDE, what is the nucleoTIDE?

adenylate

how does the nomenclature for nucleosides and nucleotides differ?

replace “-sine” in nucleoside with “-ylate” in nucleotide

what does “deoxy-base” mean?

2” OH group has been replaced with an H

why is RNA less stable than DNA?

2’ OH is reactive

how would you change the abbreviation “AMP” to reflect a “deoxy” state?

dAMP

what kinds of nucleotides are used for ENERGY?

NTPs and NDPs

what are examples of nucleotides (modified) used as SIGNALING molecules? (2)

cAMP and cGMP (cyclic NMPs)

what does c stand for in cAMPs?

cyclic

what are 2 examples as SUBSTRATES for that are derived from nucleotides?

CDP-diacylglycerol and UDP-glucose

what are 4 examples of enzyme COFACTORS that are derived from nucleotides?

SAM, NADH, FAD, CoA

what are the 2 types/mechansims of nucleotide synthesis?

linear and branches

Purines are formed using the _______ method/mechanism

branched

pyrimidines are formed using the ________ method/mechanism

linear

what does NDK stand for?

NDP kinase

what does RNR stand form?

ribonucleotide reductase

__________ are made by building the base WHILE attached to the ribose

purines

__________ are made by building the base FIRST, then attaching to the ribose

pyrimidines

production of ________ is the committed step in the purine synthesis?

PRA

what does PRPP stand for?

phosphoribosyl pyrophosphate

what is PRPP?

activated donor of ribose5P, (activated intermediate)

what is the first step in purine synthesis?

PRPP + glutamine

in the first step of purine synthesis, _________ donates a ______ group, replacing the ________ group on PRPP, forming _______

glutamine; amino; pyrophosphate; PRA

how is PRA formed? (what reaction)

reaction of PRPP with glutamine

how is PRPP formed?

addition of a pyrophosphate on carbon 1 of R5P

what drives the reaction PRA synthesis reaction forward?

hydrolysis of pyrophosphate

what enzyme used to produce PRA in purine synthesis?

Gln-PRPP amido-transferase

how many steps does it take to form IMP from PRA

9

what molecules are used to form the purine base ring structure? (5)

Gly, Gln, Asp, HCO3, N10-formyl THF

which purine substrate donates nitrogen 1?

aspartate

which purine substrate donates carbon 6?

HCO3-

which purine substrate donates carbons 4 and 5, as well as nitrogen 7?

glycine

which purine substrate donates nitrogens 3 and 9?

glutamine

which purine substrate donates carbons 2 and 8?

N10-Formyl-THF

when does the purine ring structure close? (what steps)

after the addition of a second glutamine

how many ATPs are used to form a purine ring?

4

the enzymes of purine biosynthesis are organized via _______________

substrate channeling

what are 3 benefits of substrate channeling?

protect intermediates, increase local concentrations, joint regulation

what is formed when the full purine ring structure is formed on PRA?

IMP

which is the common branching point (molecule) for the formation of AMP and GMP (purine synthesis)?

IMP

what is the first intermediate in GMP synthesis? (1st branch point)

xanthylate (XMP)

what does IMP react with to form XMP?

NAD+ and H2O

what does Xanthylate react with to form GMP?

Gln, ATP, and H2O

what is the pathway to form GMP from the purine branch point?

IMP → Xanthylate (XMP) → GMP

what is the first intermediate in AMP synthesis? (1st branch point)

Adenylosuccinate

what does IMP react with to form adenylosuccinate?

aspartate and GTP

how is adenylosuccinate converted to AMP?

removal/release of fumarate

what is the pathway to form AMP from the purine branch point?

IMP → Adenylosuccinate → AMP

what molecule is this?

IMP

what molecule is this?

XMP

how does XMP differ from IMP?

addition of another ketone group

how does adenylosuccinate differ from IMP?

replace ketone with aspartate

what molecule is this?

adenylosuccinate

purine synthesis is regulated via _________

feedback inhibition

as PRPP accumulates in the cell, it activates the enzyme _________, which catalyzes the conversion of ______ into ______

glutamine-PRPP-amidotransferase; PRPP; PRA

does PRPP activate or inhibit glutamine-PRPP amidotransferase?

activate

what enzyme catalyzes the committed step of purine synthesis?

glutamine-PRPP-amidotransferase

ATP synthesis is regulated by ______

GMP

GTP synthesis is regulated by ______

ATP

in ATP synthesis, the conversion of ______ to _____ is regulated by GTP

IMP; adenylosuccinate

in GTP synthesis, the regulation of _________ to _________ is regulated by ATP

XMP; GMP

a high [GTP] will ___________ AMP synthesis

increase

a high [ATP] will _________ GMP synthesis

increase

AMP and GMP regulate their own synthesis from ______

IMP

GMP and AMP will ________ their synthesis from IMP

inhibit

what process of ATP synthesis is inhibited by AMP?

formation of adenylosuccinate from IMP

what process of GTP synthesis is inhibited by GMP?

conversion of XMP from IMP

high levels of AMP and GMP will inhibit which enzyme?

glutamine-PRPP amidotransferase

high levels of ADP and GDP will inhibit which enzyme?

PRPP synthase