Purines and pyrimidines.........

Cell investment for purine ring synth

PRPP, 4 ATP, 2 gln, asp, gly, 2 N10-formyl-THF, CO2 (no biotin needed) $

PRPP synthetase is activated by ______ and inhibited by ________

Pi; IMP, AMP, GMP $

In orotic aciduria, the enzyme deficiency is _________

UMP Synthase

Purine synth *regulatory* step ____________ inhibited by _________ pathways end products and *activated* by _________

amido-transferase; AMP, GMP, IMP; PRPP $

2nd step of pyrimidine synth involves making carbamoyl-aspartate via _____________

aspartate transcarbamoylase (ATCase)

PRPP requires 3 AA _______ _______ (which does not require biotin) B9 as _________ to donate 1-C formyl groups _______ via HMP Uses lots of energy from ______

aspartate, glutamine, glycine CO2 (does not require *biotin*) B9 as TH4 to donate formyl groups Ribose-5-P via HMP ATP

Pyrimidines can be easily degraded into soluble molecules: ______ and _________ which are them converted to _____ and _________

b-alanine, b-amino-succino-butyrate; acetyl-CoA, succinyl-CoA

Step 5: In the conversion of nucleoside monophosphates to di and tri phosphates, the energetic exchange bank is ___________

base specific $

In pyrimadines the ring is completed ________ attachment to the ribose-5-P

before

CPS II makes _________ in the cytosol in contrast to CPS I which is used within the ______ to make CP

carbamoyl phosphate; mitochondria

Overall inhibitor of ribonucleotide reductase is

dATP $

Regulation of ribonucleotide reductase at two sites: ______ blocks activity site to prevent reduction ______ binds at additional site to regulate substrate identity

dATP; NTP

Blockage of either thymidylate synthase or dihydrofolate reductase results in the blocking of ______ synthesis

dTMP

To make ______ from UDP: reduce to dUDP, then dephos to dUMP, *methylate* to form dTMP, add pyrophosphate

dTTP

Deficiencies of adenosine deaminase will cause ________ levels to rise which inhibit ribonucleoside reductase which prevents DNA production

deoxy-adenosine $

To produce dTTP the intermediates need to be in the ____ form to become deoxy and in the ________ form to become methylated

di; mono $

Going from dUMP → dTMP: methotrxate inhibits: _______

dihydrofolate reductase

CP + water come together to form a ring which is catalysed by

dihydroorotase

The cell needs free THF to be able to pick up formate; in the _______ this is not possible → cessation of purine synth

folate trap

Sources of atoms that comprise purine nucleus are _______ and _______ which donate N only; and all of ________ and formyl-FH4 donates 1-C formyl groups

glutamine and aspartate; glycine

Pyrimidine synthesis starts with ________ and ___________ and CO2 (without biotin); the committed step involves *cytosolic* _________

glutamine, aspartate; CPS II $

Uric acid has 4 ionizable ________ atoms which makes it a powerful antioxidant that contributes _______ of our antioxidant capacity in plasma

hydrogen atoms; half

High uric acid correlates with _____ cancer incidence

low

_____________ competitively inhibits dihydrofolate reductase

methotrexate (same binding site, ↑ Km, same Vmax) $

dihydroorotate + NAD come together to form _________ via _______

orotate; dihydroorotate DH

Low levels of _________ result in abnormal growth and large amounts of *oratate* in the urine

orotidine phosphate decarboxylase $

Purine synthesized via __________ on a scaffold

phosphoribosyl-pyrophosphate (PRPP) $

Pyrimethamine inhibits ______ FH2 reductase

protozoal

Which has a salvage pathway, purines or pyrimidines?

purines

A major type of covalent change in pyrimidines is called __________ and should be corrected ASAP

pyrimidine dimerization

Step 4: In the conversion of IMP to GMP and AMP the energy sources are _________ and the enzyme is inhibited by ___________ acid

reciprocal; mycophenolic $

Uric acids can accumulate in joints from intake of rich foods such as liver, sweetbreads, _______. Essentially ones high in protein

red wine $

Ribonucleotide reductase must be in the ______ state to convert NDP → dNDP

reduced

Purines are degraded by ____________ in pancreatic juice located in the SI

ribo/deoxyribonucleases

Ribo-nucleoside di-phosphates are reduced to their deoxy forms (dADP, dUDP, dGDP, dCDP) via _________

ribonucleotide reductase $

methylene TH4 role in supplying the methyl group in the synthesis of dTMP from dUMP is controlled by ________

serine

Going from dUMP → dTMP: 5-fluorouracil inhibits ________

thymidylate synthase

Methylated cytosines can spontaneously deaminate to become ________

thymines

In Purines after portions of the nucleotide have been removed, we are left with the end product _________ which is excreted in the urine

urate

The -CH3 in thymine functions to make sure AT pairings are ______ than GC pairings to permit RNA polymerases to work

weaker

In gout, which is caused by an overproduction of uric acid is mediated by an enzyme called _______ which is competitively inhibited by __________

xanthine oxidase; allopurinol $

Defects in UV-specific DNA endonuclease can result in

xeroderma pigmentosum

Nitrogenous bases stem from 2 compounds by the addition or removal of functional groups. Purines: use ______ Pyr: use ________

IMP; OMP $

_________ is caused by the inability to salvage hypoxanthine and guanine which results in excess uric acid

Lesch-Nyhan

thioredoxin is reduced by _______ via _______

NADPH; thioredoxin reductase

In dNTP synthesis, the substrate to be reduced must always be _______

NDP

To be reduced to the deoxy state, a nucleotide must be in the ______ form and ribonucleotide reductase reduced by ________

NDP; thioredoxin

In pyr synthesis _______, ______,_______ are used to make carbamoyl phosphate

2 ATP, CO2, glutamine

_____ is the sole source of P added to mono or diphosphates

ATP

Trimethoprim inhibits _______ FH2 reductase

Bacterial

Anatomy of a nucleotide

Base → nucleoside → nucleotide (#2 carbon reduced in NADPH related step)

______ is the attachment of a formyl group (single C) produced from methylene-THF which arises from _______ interconversion

Formylation; serine/glycine

Mutations of _________ account for 33% of all cases of Lesch Nyhan

HGPRT $

There are two enzymes that salvage free purine bases: IMP and GMP use _________ AMP uses ________ and both enzymes require PRPP

HGPRT; APRT $

Re: purine ring synthesis, the 1st step involves PRPP which is made by?

Ribose phosphate pyrophosphokinase $

A severe form of adenosine deaminase deficiency can lead to _________

SCID $

Re: purine synth the 3rd step ends with synth of IMP through 9 steps involving ______ which transfer 1-C groups, and inhibition here blocks _________ synth

THF; nucleic acids $

dUMP and dUTP are catalyzed by ___________ which does not require ATP. And also utilizes __________ as the source of the methyl group

Thymidylate synthase; methylene-THF $

______ is the only base found exclusively in DNA

Thymine

Orotate phosphoribosyl transferase and OMP decarboxylase are separate domains on a single polypeptide _______

UMP synthase

Pyrimidine synth inhibited by ________ and activated by _________

UTP; ATP PRPP $

CTP is synthesized by the amination of _________ which is catalysed by __________ with an amido group donated by __________

UTP; CTP synthetase; glutamine $

___________ excises DNA at both ends of damaged sections

UV-specific endonuclease

Without ________ you cannot make THF

Vit B12