Nucleotides & Nucleic Acidschemistry.creighton.edu/~jksoukup/lec24part2.pdf · Nucleotides & Nucleic Acids Biosynthesis and Degradation Biosynthesis: De novo pathways - uses metabolic

Nucleotides & Nucleic AcidsRNA structure

Single-stranded (ss) RNAs

Nucleotides & Nucleic AcidsRNA structure - rRNA

Nucleotides & Nucleic AcidsRNA structure - tRNA, hammerhead ribozyme, Tetrahymena groupI intron (catalytic)

Nucleotides & Nucleic AcidsChemistry - denaturation

High temp/pHNo covalent bonds broken

Normal temp/neutral pH

SLOW

QUICK

Normal temp/neutral pH

Nucleotides & Nucleic AcidsChemistry - denaturation

Lowest absorption of UV light

Lower absorption of UV lightthan free nucleotides

HYPOCHROMIC EFFECT -decrease in absorption as you go from free nt → single strands → doublestranded(can monitor transition from ds to ss)

Nucleotides & Nucleic AcidsChemistry - heat denaturation

rela

ted

to a

bsor

ptio

n

Nucleotides & Nucleic AcidsChemistry - denaturationElectron microscopy

Nucleotides & Nucleic AcidsSequencing

3’ 2’

Nucleotides & Nucleic AcidsSequencing

Nucleotides & Nucleic AcidsBiosynthesis and Degradation

Biosynthesis:De novo pathways - uses metabolic precursors (AAs, ribose 5-phosphate, CO2, NH3)

Salvage pathways - recycle free bases and nucleosides releasedfrom nucleic acid breakdown

Nucleotides & Nucleic AcidsBiosynthesis:De novo pathways

Nucleotides & Nucleic AcidsBiosynthesis:De novo pathways - regulation

Nucleotides & Nucleic AcidsDegradation:

Allopurinol

Nucleotides & Nucleic AcidsDegradation:

Deficiency in adenosine deaminase (causes ADA deficiency)Cannot break down adenosine, so it builds up, also [dATP] builds up

dATP is an inhibitor of ribonucleotide reductase, high [dATP] causesgeneral deficiency of other dNTPS in lymphocytes

Poor development of T and B lymphocytes, ineffective immune system

Leads to severe combined immunodeficiency syndrome (SCIDS), alsocalled “bubble boy” disease

First gene therapy for ADA

Elevated uric acid in bloodCaused by deficiency of one of purine metabolic enzymes

Causes gout

Uric acid causes inflammation of joints, problems in kidneys

Treatment = Drug allopurinol, which is an inhibitor of xanthineoxidase (enzyme that catalyzes step that makes uric acid)

Nucleotides & Nucleic AcidsChemotherapeutic drugsCancer cells grow rapidly, so they are in constant need of nucleotidesCancer cells more sensitive than normal cells to inhibitors of nucleotidebiosynthesis

Analogs of glutamine

Used in de novo synthesis

Nucleotides & Nucleic AcidsChemotherapeutic drugsTarget enzymes