NUCLEIC ACIDS & NUCLEOTIDE METABOLISM

Nucleic Acids

Polymers of nucleotides (DNA and RNA) that store and transmit genetic information.

Nucleotide

Monomer of nucleic acids consisting of a sugar, a base, and a phosphate group.

Nucleoside

Sugar + base; lacks the phosphate group.

Purines

Double-ring bases (adenine and guanine).

Pyrimidines

Single-ring bases (cytosine, uracil, thymine).

Phosphodiester Bond

Chemical linkage between nucleotides forming the backbone of nucleic acids.

5' End

End of DNA/RNA strand with a free 5' phosphate.

3' End

End of DNA/RNA strand with a free 3' hydroxyl.

Ribose vs 2'-deoxyribose

RNA uses ribose; DNA uses 2'-deoxyribose.

NTPs and dNTPs

Ribonucleoside triphosphates for RNA; deoxyribonucleoside triphosphates for DNA.

Purines (Adenine and Guanine)

Two-ring bases essential for DNA/RNA; abbreviated as A and G.

Pyrimidines (Cytosine, Uracil, Thymine)

Single-ring bases; C, U (RNA), T (DNA).

Chargaff's Rule

In DNA, A pairs with T and G pairs with C; purines equal pyrimidines.

Antiparallel

DNA strands run in opposite 5' to 3' directions.

DNA Double Helix

Two anti-parallel DNA strands forming a right-handed helix..

Major Groove

Large groove in the DNA helix where proteins often bind.

Minor Groove

Smaller groove in the DNA helix involved in protein contacts.

Hydrogen Bonding in base pairs

A–T forms 2 H-bonds; G–C forms 3 H-bonds.

GC vs AT Bonds and Melting

GC-rich regions have higher melting temperatures due to extra H-bonds.

Denaturation (melting)

Separation of DNA strands when heated or disrupted.

Annealing (hybridization)

Reformation of double-stranded DNA from complementary strands.

Nucleosome

DNA wrapped around a histone protein core; basic unit of chromatin.

Chromatin

DNA plus protein (histones) that packages genetic material.

Histones (H2A, H2B, H3, H4)

Core histones forming the histone octamer around which DNA winds.

Linker Histone H1

Histone that helps package linker DNA between nucleosomes.

Topoisomerases

Enzymes that relieve DNA supercoiling; Type I (cuts one strand) and Type II (cuts both strands).

Nucleotide Synthesis

Biochemical pathways to build nucleotides from precursors.

De Novo Biosynthesis

Nucleotide synthesis from basic precursors (amino acids, CO2, etc.).

Salvage Pathways

Recycling of bases to nucleotides from turnover or diet.

PRPP

5-Phosphoribosyl-1-pyrophosphate; activated ribose donor for nucleotide synthesis.

PRPP Synthetase

Enzyme that makes PRPP from ribose-5-phosphate.

Amidophosphoribosyl Transferase

Committed step in purine biosynthesis; adds amide nitrogen from glutamine to PRPP.

IMP

Inosine monophosphate; precursor to AMP and GMP.

Hypoxanthine

Purine base found in IMP.

AMP

Adenosine monophosphate; purine nucleotide.

GMP

Guanosine monophosphate; purine nucleotide.

GTP

Guanosine triphosphate; energy/regulatory role in synthesis.

ATP

Adenosine triphosphate; energy/regulatory role in synthesis.

PRPP Activation in Purine/Pyrimidine Synthesis

PRPP acts as an activator for both purine and pyrimidine biosynthetic pathways.

Purine Regulation (Feedback/Feedforward)

Involves inhibition by ADP, GDP, XMP and activation by PRPP; coordinates AMP/GMP production.

CAD Complex

CPS II, aspartate transcarbamoylase, and dihydroorotase; first three steps of pyrimidine biosynthesis.

Orotate

Intermediate leading to UMP in pyrimidine synthesis.

UMP/UDP/UTP

Pyrimidine nucleotides; UTP used for RNA synthesis and for further conversion to CTP.

CTP

Cytidine triphosphate; formed from UTP by CTP synthase.

Ribonucleotide Reductase (RR)

Enzyme that reduces NDPs to dNDPs, providing the building blocks for DNA.

dNTPs

Deoxyribonucleotide triphosphates used for DNA synthesis.

dCMP → dUMP → dTMP pathway

Sequential conversion yielding dTTP via dCMP/dUMP/dTMP steps (involves thymidylate synthase).

Thymidylate Synthase

Enzyme that converts dUMP to dTMP using a folate cofactor.

THF (Tetrahydrofolate)

Folatederivative that donates one-carbon units for dTMP synthesis.

Dihydrofolate Reductase (DHFR)

Regenerates THF from DHF; essential for maintaining one-carbon pool.

Folate Cycle Serine to Glycine

Pathway regenerating THF to donate methyl groups for dTMP synthesis.

5-Fluorouracil (5-FU)

Antimetabolite that inhibits thymidylate synthase after activation to 5F-dUMP.

Methotrexate (MTX)

Folate analog; inhibits DHFR; blocks THF production and dTMP synthesis.

HGPRT

Hypoxanthine-guanine phosphoribosyltransferase; salvage enzyme for purines.

Uric Acid

End product of purine degradation; excreted in urine.

Allopurinol

Xanthine oxidase inhibitor; reduces uric acid production.

Gout

Disease from excess uric acid; treated with allopurinol.

Purine Degradation

Breakdown of purines to uric acid.

Nucleotidases/Nucleoside Phosphorylases

Enzymes that generate bases and ribose-nucleotides from nucleotides/nucleosides.

Nucleotide Salvage

Recycling bases into nucleotides using PRPP and salvage enzymes.

BRCA1/BRCA2

Tumor suppressor genes; mutations predispose to breast/ovarian cancer; involved in HDR.

HDR (Homology-Directed Repair)

DSB repair using a homologous sequence as a template.

DNA Damage Response

Cellular pathways activated by DNA damage leading to repair or apoptosis.

Therapeutic Index

Ratio indicating drug safety window; higher TI preferred; relates to cancer chemotherapy.

Chemoresistance

Tumor cells adapt to survive chemotherapy; often via enhanced DNA repair.

Ionizing Radiation (IR)

Radiation that induces DNA damage including strand breaks and ROS.

Double-Strand Break Repair (HR)

Repair of DSBs using a homologous sequence as template (homology-directed repair).