Humboldt State University ® Department of Chemistry

Richard A. Paselk

	VUB Biology	Fall 2001
Lecture Notes:: 24 September	© R. Paselk 2001

Biomacromolecules

Nucleic Acids and Nucleic Acid Structure 

Two major types of nucleic acids, DNA and RNA. (overhead, MvH 4.2)

In each case we see a polymer made by linking nucleotides via phosphodiester bonds. Biologically these bonds are synthesized by the attack of an alcohol residue from ribose on the a-phosphate to release a diphosphate residue, which is subsequently hydrolyed to phosphate (helps to drive synthesis to completion):

DNA DeoxyriboNucleic Acid: (overheads)

• Antiparallel double helix.
• Bases are in center, away from water, and H-bonded between chains, forming base pairs.
• Uses deoxyribose as sugar (2'-OH is replaced by H).
• Very stable to hydrolysis (no 2'-OH to catalyze).
• Sugar phosphate groups linked together on periphery
• Structure has major and minor grooves.
• Complementary base pairing occurs between A & T and G & C.
• Each strand thus acts as a template for its complement.
• Only the two normal "Watson-Crick" base-pairs have the correct dimensions to give a double-helix without bumps or dips - this greatly contributes to the fidelity of replication since others will not fit in replicating enzyme (DNA Polymerase).

RNA RiboNucleic Acid:

• Uses ribose as sugar.
• Chemically less stable to hydrolysis.

Functions of Nucleic Acids

DNA: DNA is largely used for information storage. As such it is a very stable molecule with very precise replication and precision.

RNA: RNA is mostly an adaptor molecule, used to translate between information in DNA and protein machinery/structure. Three kinds of RNA:

• mRNA - a transcription of the information in the DNA. Used to carry the information in temporary format from the DNA archive to the protein synthetic machinary.
• tRNA - an adaptor molecule. Classic "clover-leaf" shape (secondary structure) folds up into a 3D L-shape (tertiary structure). The proper amino acid is attached to the CCA end by an enzyme specific for the amino acid and for the tRNA. One arm, the anticodon loop, recognizes the code for an amino acid on the mRNA.
• rRNA - This RNA forms the core of a large molecular machine, the ribosome, which is used to make proteins. The ribosome consists of 3-4 RNA molecules and many proteins (c. 100 in eucaryotes). BOth RNA and proteins are involved in catalysis.

Proteins

Proteins are polymers of amino acids

Can be fibrous or globular

3D Structure of Proteins

In order to understand and categorize their organization, protein structure has been divided into four hierarchical levels and a couple of sublevels:

• Primary structure (1°) : the linear order or sequence of peptide bonded amino acid residues, beginning at the N-terminus. (Characteristic bond type: covalent.)
• Secondary structure (2°): the steric relations of residues nearby in the primary structure which give rise to local regularities of conformation. These structures are maintained by hydrogen bonds between peptide bond carbonyl oxygens and amide hydrogens. The major secondary structural elements are the alpha helix and the beta strand. (Characteristic bond type: hydrogen.)
• Tertiary structure (3°): the steric relations of residues distant in the primary sequence; the overall folding pattern of a single covalently linked molecule. (Characteristic bond type: hydrophobic; others: hydrogen, ion-pair, van der Waals, disulfide.) Two sub-levels have been identified which often occur within the tertiary level of structure:
  • Super secondary structure (motifs): defined associations of secondary structural elements. (Characteristic bond type: hydrogen & hydrophobic.)
  • Domains: independent folding regions within a protein. (Characteristic bond type: hydrophobic; others: hydrogen, ion-pair, van der Waals.)
• Quarternary structure (4°): the association of two or more independent proteins via non-covalent forces to give a multimeric protein. The individual peptide units of this protein are referred to as subunits, and they may be identical or different from one another. (Characteristic bond type: hydrophobic; others: hydrogen, ion-pair, van der Waals.)

ENZYMES

Enzymes are the heart of Biochemistry

• protein based catalysts (for us RNA based catalysts are Ribozymes)
• enormously effective catalysts: typically enhance rates by 10⁶ to 10¹² fold
• operate under mild conditions: 0 - 100 °C (or even 300+ for some bacteria), 20 -40 °C for most organisms; and low pressures (atmospheric)
• very specific: generally catalyze reaction for a very restricted group of molecules, sometimes for a single naturally occurring molecule of a single chirality.

Enzymes generally have a cleft for active site, generally <5%of surface: look like pac man. Need large structure to maintain shape etc. with many weak bonds.

Models for Enzyme Specificity:

• Lock & Key model of Fischer: diagram; Hexokinase example: reaction, methanol and water as ineffective picks. [overhead 8-13, S]
• Induced-fit model of Koshland: diagram; space-filling models of HK with and without substrate. (Figure 15.1, p 462, G&G) [overhead 8-13, S; 16-5, V&V{HK}]
  

Types of specificity:

• Geometric specificity: shape (overhead 12-1, V&V]
  • Chiral specificity: most chirally specific enzymes are absolutely stereospecific.
• Chemical specificity: functional groups, types of chemical reaction.

Carbohydrates

The important aldoses (Figure 8.1, p 197) [overhead 9.4 P] include the five carbon aldopentose, ribose:

which commonly occurs in the cyclic furanose form.

The six carbon aldohexoses, glucose, mannose, and galactose: {Models of glucose, linear and ring forms, may be viewed by clicking on the buttons at this site.} These aldohexoses commonly occur in the six-membered "pyranose" ring form (glucopyranose below):

The six carbon ketohexose, fructose, is the other important hexose: (A model of fructose, in the ring form, may be viewed by clicking on the buttons at this site.}

Fructose commonly occurs in a cyclic five-membered ring form.

DISACCHARIDES

Can link sugars via acetal bonds, known as glycosidic bonds.

There are four common disaccharides [overhead 9.24, P]:

• maltose [a-D-Glucopyranosyl-(1,4)-b-D-glucopyranose]
• cellobiose [b-D-Glucopyranosyl-(1,4)-b-D-glucopyranose]
• lactose [b-D-Galactopyranosyl-(1,4)-b-D-glucopyranose], and
• fructose [a-D-Glucopyranosyl-(1,2)-b-D-fructofuranoside]

The first three are reducing sugars, that is they have "free" aldehyde groups, whereas fructose has both carbonyl groups tied up in the relatively stable glycosidic bond. Maltose and fructose are joined in a-glycosidic bonds. In general the a-glycosidic bond is easily cleaved (it is less stable chemically and organisms have enzymes to cleave it) whereas the b-glycosidic bond is very difficult to break down.

Thus for cellobiose, and more importantly, cellulose which is also linked by b-bonds, essentially only bacteria can digest this bond.

Animals also can't digest (possible exception of snails). You may ask, What about Cows and things? Well they use bacteria. Cows for instance are basically walking fermentation tanks. Cool biological examples: Desert Iguana consume feces to maintain culture; Rabbits eat and reprocess first pass feces (soft) to take advantage of fermentation; Multiple stomachs in Ruminants; Ultimate symbiosis in some termites: protozoans in gut have bacteria in gut, and use spirochetes as "cilia" (rowers).

Sucrose, Sucrase (Invertase), and the magic of liquid filled chocolate covered cherries.

POLYSACCHARIDES

Can have both homo- and heteropolysaccharides. We will focus on homopolysaccharides as most central, but will mention some heteropolysaccharides to illustrate their functions. Homopolysaccharides have a single type of residue. Most common contain glucose. Used for energy (food) storage (starches and glycogen) and structure (cellulose).

Starch (energy storage in plants). Two kinds

• Amylose: linear, a-1,4 glycosidic links. MW: 4,000 - 150,000. [Fig 5.6, p 62; 5.7, p 63] (Gives char. deep blue color with iodine due to coiled complex enclosing iodine-color is lost with heating, returns as cooled).
• Amylopectin: branched every 30 or so units­linear a-1,4 chain of 30 glu residues then a-1,6 branch point. of course get branches on branches as well. MW: ->500,000. [Fig 5.6, p 62] Broken down by a-amylase (pancreas and salivary glands; random cleavage of a-1,4 links) to give glucose and maltose; or b-amylase (plants; hydrolyses from reducing ends to give maltose). When either of these enzymes attack amylopectin they are blocked when they reach or are near a branch, thus end up with a "limit dextrin."

Glycogen: animal starch. Just like amylopectin, but more highly branched (every 8-12 residues). This allows more free ends for more rapid breakdown­important in animals.

STRUCTURAL POLYSACCHARIDES

Cellulose: b-1,4 linkages, thus resistant to breakdown (including acid hydrolysis) as want for structure (don't want to digest self). Multiple, extended strands come together as fibrils held together with H-bonds (Fig 5.7, p 63; 5.8, p 64), laid down in cell wall in criss-cross pattern, glued together with polyalcohols (lignin).

Chitin: Serves similar role to cellulose, but in animals (crustaceans and insects), fungi, and some algae. Homopolymer of N-acetyl-D-glucosamine. Like cellulose , it has b-1,4 linkages, and is thus resistant to breakdown. (p 65)

Among the heteropolysaccharides are the glycans such as Hyaluronic acid, an alternating polysaccharide of D-glucuronic acid and N-acetyl-D-glucosamine; MW to 5,000,000 which serves as a lubricant in joints and is a component of the vitreous humor. Again we see b-1,4 linkages.

Lipids

Types of Lipids: (overhead 11.1, P)

• Fatty acids: long chain carboxylic acids. (Figure 5.10, p 65, 5.11, p 66) [overhead 11.2, P; 12-3, S].Three of the most common are:
  • Palmitic acid: (You can view an on-line model by clicking the Palmitic acid button at this site.)

• Stearic acid:

• Oleic acid: (You can view an on-line model by clicking the Oleic acid button at this site.)

• Triacylglycerols: Three fatty acids esterified to glycerol. (Figure 5.10, p 65) [overhead 11.6]
• Glycerophospholipids: Two fatty acids and a phosphate esterified to glycerol. (Figure 5.12, p 67) [overhead 11.8]:

Lipid Properties: An important consideration for lipids of all sorts is their fluidity. Thus membranes must be fluid enough to allow the diffusion of proteins, transport processes etc. but not so fluid as to weaken the membranes structure. For storage want fat to be fluid enough to flow to fill out body shape at normal operating temperatures. A number of strategies are used by organisms to adjust lipid fluidity:

• Fatty acid chain length: longer chains have higher melting points (less fluid at a given temperature).
• Unsaturation: double bonds introduce a "kink" in the chain, harder to stack, so less van der Waals contact and thus lower melting points (more fluid).
• Branched chains (bacterial only): Again, less van der Waals contact and thus lower melting points (more fluid).
• Cholesterol: Its planar shape enables it to stiffen bilayers

Lipid Bilayers

Detergents & Micelles: Polar heads of detergents and soaps (such as long chain fatty acids) tend to associate with polar solvents such as water, while non-polar "tails" are excluded by water and are forced to associate with themselves making globules known as micelles.

Lipid Bilayer: Figure 5.13, p 67 [overhead 11-12, V&V; 12-11]:

The lipid bilayer forms the core for the lipid bilayer membrane as seen in the Fluid Mosaic Model of biological membranes which we will look at later in cells.

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Last modified 24 September 2001

© R Paselk