Lecture 3 Summary

Chemical properties of water. Nucleic acids. Lipids and biological membranes.

Nucleic acids are one the major classes of biological macromolecules. The nucleic acids DNA and RNA are the carriers of information in living cells and viruses. DNA (deoxyribonucleic acid) is the physical realization of the genes and genomes of cellular organisms, while RNA (ribonucleic acid) in most cases mediates expression of the genetic information stored in DNA. Nucleic acids are typically long polymers built up of repeating units called nucleotides. A nucleotide is a combination of a base with a sugar (usually ribose or deoxyribose) and phosphate that include the ribonucleotides and deoxyribonucleotides of RNA and DNA, respectively. A nucleoside is the base and sugar part of a nucleotide, making the latter a phosphate ester of a nucleoside.

Nucleotides can be joined together in a series of phosphodiester linkages to form a nucleotide polymer, or polynucleotide. The 3' hydroxyl of one nucleotide forms an ester with the phosphate attached to the 5' hydroxyl group of another to form a dinucleotide. The chain can be extended to arbitrary length by formation of additional phosphodiester bonds with more nucleotides. There is a directionality to the chain that is specified notationally as the 5'→3' or 3'→5' directions, by reference to the 5' position (hydroxymethylene group exo to the aldopentose ring of ribose or deoxyribose) and the 3' position (3' OH attached directly to the ring) of the sugar part of the backbone. By convention, a polynucleotide sequence can be represented by the single letter symbol for a base, with the first letter listed the 5' end and the last letter listed the 3' end.

Left: Structural drawing of a polyribonucleotide, along with symbolic representations of the four common bases of ribonucleotides and RNA molecules. The directionality of the chain is indicated.

Double-stranded DNA

When two polynucleotide sequences show reverse complementarity, they can form an extended stretch of a perfectly base-paired double-stranded structure held together by many hydrogen bonds. There are three stereochemically distinct types of regular double-stranded helical polynucleotide structures. These are A-form, B-form, and Z-form. The B-form is the most common for DNA.

Diversity in the RNA world

RNA molecules show great diversity in structure and function. A single-stranded polyribonuclotide can fold back upon itself to form a variety of hairpin and stem-loop structures containing antiparallel, double-stranded helical regions featuring the canonical, Watson-Crick base pairs shown above. The favored confomation for an RNA helix is the A-form. This pattern of base-paired and loop regions can be thought of as RNA secondary structure (by analogy to protein structural hierarchy).

Untranslated RNA species are now being implicated in disease. Mutant forms of these RNAs have recently been linked to Fragile X tremor / ataxia syndrome (FXTAS) and myotonic dystrophy.

A ribozyme is an RNA molecule that catalyzes a chemical reaction. Examples include the self-splicing Group I intron from Tetrahymena, the "hammerhead" ribozyme, and the hairpin ribozyme. The RNA components of the ribosome could also be included, as biochemical, genetic, and structural evidence shows that the RNA, and not the protein components, catalyze the reactions of protein synthesis. The catalytic repertoire of ribozymes is limited mainly to phosphoryl transesterification and hydrolysis reactions.

Lipids and membranes

Many lipids, such as triacylglycerols and phospholipids are based on fatty acids. Lipids found in biological membranes include phospholipids, glycolipids, and cholesterol. The spontaneous formation of phospholipid bilayers and vesicles provides a physicochemical starting point for study of membranes in cells. Properties of lipid bilayers such as permeability and fluidity are key underpinnings to understanding the roles of membrane-associated proteins.

Acid-base chemistry: Definition of pK_a and the Henderson-Hasselbalch equation

In biochemistry, especially in discussion of amino acid and protein chemistry, we will make frequent use of the concept of pKa of an ionizable group. Starting with the chemical equation for the ionization of a weak acid, the acid dissociation equation (top equation), we derive the usual equilibrium expression, giving the equilibrium constant the special designation Ka (2nd equation). Taking the negative logarithm (base 10) of both sides of this equation leads to a definition of pKa in terms of pH and the log(10) of the ratio of concentrations of the anionic conjugate base and unionized acid (not shown).

Learning objectives

• Perform all relevant applications from study of acid-base equilibria (pH calculations for strong acids and bases, weak acids or weak bases, buffers; treatment of polyprotic systems, Henderson-Hasselbalch equation, definition and interpretation of titration curves).

Page updated 9-7-09

References

1. Voet D, Voet JG, Pratt CW. (2008). Fundamentals of Biochemistry (3rd ed.) Ch.2, pp.30-36.
2. Dowhan W. (1997) Molecular basis for membrane phospholipid diversity: Why are there so many lipids? Annu Rev Biochem 66: 199-232.