Ch. 32: Nucleotides and their Polymers

nucleotides

building blocks of nucleic acids

functions of nucleotides

store and transfer genetic information (DNA and RNA), energy currency (ATP and GTP), signaling molecules (cAMP and G-proteins), coenzymes (NAD+ and FAD)

components of nucleotides

five-carbon sugar, nitrogenous base, at least one phosphate group

pyrimidines

nitrogenous bases with 1 ring with 4 carbons and 2 nitrogens (C, U and T)

pyrimidine used in RNA and DNA, can spontaneously deaminate to uracil

cytosine

pyrimidine used in RNA, unstable

uracil

pyrimidine used in DNA, methylated for stability

thymine

purines

nitrogenous bases with imidazole fused to a pyrimidine ring (A and G)

purine with amine group

adenine

purine with amide

guanine

nucleotide synthesis

“de novo (from new)” multiple steps, highly regulated, uses LOTS of energy

nucleotide salvage

uses free bases, adds a sugar in 1 step

nucleotide degradation/catabolism

become smaller compounds

pyrimidine synthesis

made from glutamine (nitrogens), aspartate (nitrogens), 5-phosphoribosyl-1-pyrophosphate PRPP (sugar), tetrahydrofolate-Vitamin B9 (carbons), makes orotidine 5’ monophosphate (OMP)

regulation of pyrimidine synthesis

inhibited by CTP, activated by ATP

carbamoyl phosphate synthase II (CPS2)

catalyzes first committed step in pyrimidine synthesis, takes glutamine, 2 ATP and CO2 to form carbamoyl phosphate

ribonucleotide reductase

reduces UDP to dUDP, CDP to cCDP

purine synthesis

made of glutamine (nitrogens), aspartate (nitrogens), glycine (helps build rings), tetrahydrofolate-Vitamin B9 (carbons), and PRPP (sugar), makes Inosine-5’-Monophosphate (IMP)

1st step in purine synthesis

starts with PRPP (sugar), adds base to sugar

regulation purine synthesis

IMP, GMP, AMP (pathway products) inhibit synthesis

pyrimidine catabolism

cytosine deaminates to uracil, and uracil and thymine are degraded to produce acetyl coA and succinyl coA

pyrimidine salvage

cytosine/uracil degraded to produce UMP, thymine degraded to produce dTMP

purine catabolism

adenosine and guanosine degraded to produce uric acid, toxic products

purine salvage

accounts for 90% of daily purine synthesis (reduces uric acid), HGPRT catalyzes addition of PRPP

hypoxanthine guanine phosphoribosyl transferase (HGPRT)

catalyzes addition of PRPP sugar in purine salvage