LECTURE 7 15 Sept 99
Nucleic Acids
Recall the 5 bases: C, U, T, A, G
Nucleosides
When a base is combined with a sugar via a b -glycosidic bond, a nucleoside is formed (Figure 3.21).
Sugar is either ribose or 2-deoxyribose and is in furanose form.
If base is pyrimidine, b -glycosidic bond is to N-1
cytosine + sugar = cytidine
uracil + sugar = uridine
thymine + sugar = thymidine
If base is purine, b -glycosidic bond is to N-9
adenine + sugar = adenosine
guanine + sugar = guanosine
If sugar is 2-deoxyribose, nucleoside is a 2¢ -deoxynucleoside.
Nucleotides
Nucleotides are nucleosides with phosphate attached via an ester bond, as in 5¢ -AMP (adenosine monophosphate).
Nucleotides may contain 1, 2, or 3 phosphate groups, as in the series AMP, ADP (adenosine diphosphate), ATP (adenosine triphosphate).
The 2nd and 3rd phosphates are joined to the compound by anhydride bonds (acid + acid ® anhydride + H2O).
Nucleotides - 2 important biological roles
1. the monomeric units that are polymerized to form the nucleic acids.
2. important metabolic intermediates º substances involved in metabolic reactions
ATP: transfer of chemical energy in metabolism;"the energy currency of the cell"
GTP: provides energy for protein synthesis
CTP: provides energy for phospholipid synthesis
UTP: involved in the metabolic transformations of carbohydrates
Nucleic Acids Are Polymers of Nucleotides Joined by Phosphodiester Bonds
Two kinds:
1. RNA: ribonucleic acid
sugars are all ribose; bases are C, U, A, G
2. DNA: deoxyribonucleic acid
sugars are all 2-deoxyribose; bases are C, T, A, G
Polymer backbone is O-P-O-C5¢ -C4¢ -C3¢ -O-P-etc.; convention is to read in the 5¢ ® 3¢ direction.
The bases are side groups along the sugar-phosphate backbone. Genetic information is encoded within the sequence of bases.
DNA Is a Double Helix (Figures 3.22, 3.23. See also web figures)
2 strands of DNA running in opposite (antiparallel) directions
Bases inside, sugar-phosphate backbone outside
Held together by H bonds between specific base pairs (base-pairing):
A pairs with T
G pairs with C
Chargaff's Rules:
[A] = [T]
[G] = [C]
[purines] = [pyrimidines]
Base Pairs Are Virtually Identical in Size (web figure)
Watson & Crick's great insight was that the A:T and G:C base pairs represent spatially invariant substructures within DNA.
A:T base pairs held by 2 H bonds.
G:C base pairs held by 3 H bonds.
Base pairs in DNA 'stack up' like steps in a helical staircase 3.4 A (0.34 nm) apart - hydrophobic interactions
DNA has a major groove and a minor groove.
DNA is a relatively uniform cylinder, 20 A (2 nm) in diameter. Exterior is ionic (negatively charged phosphates).
Information (base sequence) is inside.
Watson & Crick, 1953 Nature paper on website:"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."
The rules of base pairing mean that if you know the sequences of nucleotides in one DNA strand, you also know the sequence in the other:
5¢ ATGCGTAT 3¢
3¢ TACGCATA 5¢
Obvious consequences to:
Replication of DNA (biosynthesis of a new double helix)
Inheritance of genetic information
DNA is the material of heredity
The set of instructions ("recipe") for making an organism, NOT a blueprint!
E. coli Chromosome - 4.64 x 106 base pairs
0.34 nm x 4.64 x 106 = 1.6 mm length, 0.000002 mm diameter
If the E. coli chromosome was magnified to appear 1 mile (1.6 km) long, it would have a diameter of 2 mm. (DNA is essentially"1-dimensional").
The total amount of DNA in a single human cell has a length of 6 feet!
The DNA in a typical human would stretch from here to the sun and back 500 times!
RNA Comes in 3 Varieties, All Single-Stranded
but with large amounts of intrastrand H bonds formed between intrachain complementary regions
1. Ribosomal RNA (rRNA): ribosome structure
2. Transfer RNA (tRNA): amino acid delivery to ribosomes
3. Messenger RNA (mRNA): the message or information specifying the amino acid sequence of a protein.
Each amino acid in the protein sequence is specified by a 3-base (triplet) sequence of nucleotides in mRNA. These triplets are called codons.
These 3 varieties of RNA are integral parts of the molecular machinery for synthesizing proteins. All 3 of these RNAs are copied from DNA sequences (RNA genes) in the chromosome.
Information Flow In Cells:
DNA ® transcription ® mRNA ® translation ® protein
Replication
agents of cellular function