Lecture 4 – Macromolecules continued – 9/7/01

The surfaces of proteins have specific shapes

Shape is crucial to the functioning of some proteins.

An enzyme must bind substrates correctly, and the correct surface shape allows for that.

Examples are carrier proteins in the cell surface membrane, ribosomes, which synthesize proteins, and the binding of chemicals (hormones) to a cell surface membrane.

Multi-component proteins are held together by their shape, charges, hydrophobic properties, and, occasionally, disulfide bonds.

It is the combination of attractions, repulsions, and interactions that determines the right fit. (See Figure 3.8.)

Hen Lysozyme:  Fig 3.6:  Cn3D.local: Hen.lysozyme.1DPX.prt

Hydrophobicity backbone: Blue: hydrophilic and red: hydrophobic.

This structure was determined from x rays of a crystal!  Doesn't show flexibility.

How to make two alpha helices “sticky” – adhere to one another

      Remember that the R groups project from the core of the helix
      There may be repeated sets of R groups projecting from the same side of a helix, called interactive motifs.  A common one is referred to as a Leucine zipper (coiled coil structure).
      Leucines, Isoleucines, Valines will interact as hydrophobics from one alpha helix to another, thus stabilizing intra- and inter-molecular structure.
      This is a common structure in a heterodimeric DNA transcription factor;  the leucine zipper stabilizes the tertiary or quaternary structure of a hetero or homodimeric relationship of these molecules.

Chaperonins help shape proteins

Chaperonins are specialized proteins that help keep other proteins from interacting inappropriately with each other prior to positioning.

Some chaperonins help folding, some prevent folding until the appropriate time. (See Figure 3.10.)

Carbohydrates: Sugars and Sugar Polymers

Carbohydrates are carbon molecules with hydrogen and hydroxyl groups.

They act as energy storage and transport molecules.

They also serve as structural components.

Carbohydrate monomers have molecular weights of approximately 100 daltons.

Polymers composed of monomers can have molecular weights of up to hundreds of thousands of daltons.

There are four major categories of carbohydrates:

      Monosaccharides

      Disaccharides, which consist of two monosaccharides

      Oligosaccharides, which consist of between 3 and 20 monosaccharides

      Polysaccharides, which are composed of hundreds to hundreds of thousands of monosaccharides

The general formula for a carbohydrate monomer is multiples of CH2O, maintaining a ratio of 1 carbon to 2 hydrogens to 1 oxygen.

During the polymerization, which is a condensation reaction, water is removed. As a result, the carbohydrate polymers have ratios of carbon, hydrogen, and oxygen that differ somewhat from the 1:2:1 ratios of the monomers.

Monosaccharides are simple, single sugars

All living cells contain glucose (C6H12O6).

Green plants produce monosaccharides; other organisms acquire glucose, or the energy to make it, from plants.

Cells break down glucose to release energy, with the final products being carbon dioxide and water.

Glucose exists as a straight chain and a ring. (See Figure 3.11.)

The ring form is predominant (>99%). There are two forms of the ring: alpha-glucose and beta-glucose.

The two forms exist in equilibrium when dissolved in water.

Different monosaccharides have either different numbers or arrangements of carbons. (See Figure 3.12.)

Most monosaccharides are optical isomers.

Hexoses (six-carbon sugars) include the following structural isomers: glucose, fructose, mannose, and galactose.

Two examples of pentoses (five-carbon sugars) are ribose and deoxyribose, which make up the backbones of nucleic acids (RNA and DNA).

These pentoses are not isomers. Deoxyribose is missing an oxygen atom at carbon 2. This results in a functional distinction between DNA and RNA.

Glycosidic linkages bond monosaccharides together

Glycosidic linkages are created by enzymes and are condensation reactions.

Disaccharides have just one such linkage.

                  Sucrose (table sugar) is glucose bonded to a fructose.

                  Lactose (milk sugar) is glucose bonded to a galactose.

                  Maltose has two beta-linked glucose molecules.

                  Cellobiose also has two glucose molecules, but they are beta-linked.

Figure 3.13 shows the two possible glycosidic linkages.

Maltose and cellobiose have the same chemical formula but are structural isomers.

The shape difference changes the biological nature of the molecules.

Enzymes that break down maltose fail to break down cellobiose.

Humans can break down maltose, but not cellobiose.

Polysaccharides serve as energy stores or structural materials

Polysaccharides are giant chains of monosaccharides connected by glycosidic linkages.

Cellulose is a giant polymer of glucose alone joined by beta-1,4 linkages. (See Figure 3.14.)

Starch is a polysaccharide of glucose with alpha-1,4 linkages.

Starch can be readily degraded by the action of chemicals or enzymes, making it a good storage medium.

Cellulose is much more stable chemically than starch and more difficult to hydrolyze chemically and enzymatically. This quality makes it an excellent structural material.

Starches vary by amount of branching. (See Figure 3.14.)

Plant starch, called amylose, is slightly branched.

Animal starch, called glycogen, is highly branched.

Starches are molecules that store glucose.

Each polymer molecule has essentially the same effect as one monomer molecule on the osmotic pressure of a solution.

Combining many glucose molecules into just one reduces the osmotic effect, allowing storage of lots of energy, without disturbing the water content of a cell too much.

Chemically modified carbohydrates contain other groups

The addition of functional groups modifies carbohydrates. (See Figure 3.15)

Amino groups can be substituted for an —OH, making an amino sugar such as glucosamine and galactosamine.

Amino sugars are important to the extracellular matrix, the systems that hold tissues together.

Galactosamine is a major component of cartilage, which is found in your ears, nose, and kneecaps.

A glucosamine derivative is a component of chitin, the polysaccharide in the skeletons of insects, prawns, and crabs. It is also found in the cell walls of fungi. Chitin is one of the most abundant substances on earth.

Nucleic Acids: Informational Macromolecules

Nucleic acid polymers are linearly arranged informational molecules.

Two types of nucleic acid polymers are DNA (deoxyribonucleic acid) and RNA (ribonucleic acid).

The DNA molecules of humans are enormous polymers that encode hereditary information bound in nucleotides.

More than 130 million nucleotides are found in just one human chromosome of average length.

In non-reproductive cell activities, information stored in DNA is transferred to RNA molecules.

The average length of an RNA molecule, although occasionally thousands of bases in length, is much shorter than a DNA molecule.

A DNA molecule contains information necessary for the production of many different RNA molecules. DNA molecules can code for RNA molecules repeatedly over the life of a cell.

The information in RNA molecules is decoded to specify the sequence of amino acids in proteins.

The nucleic acids have characteristic structures and properties

DNA differs from RNA due to the absence of the oxygen in the 2-carbon position of the ribose.

DNA typically is double-stranded: Two separate polymer chains are associated together. The association is not haphazard, but complementary.

At each position where a purine is found on one strand, a pyrimidine is found on the other.

Purines have a fused double-ring structure.

Pyrimidines have just one ring.

Pairing of a purine with a pyrimidine maintains three rings in the center of the molecule, so the backbones of the two strands maintain a constant distance along the length of the double-stranded molecule.

DNA and RNA polymers are enzymatically made and, like all the other polymers mentioned so far, are created with condensation reactions.

The linkages that hold the nucleotides in the polymer are called phosphodiester linkages. (See Figure 3.17.)

These linkages are formed between carbon 3 of the sugar (ribose in RNA, deoxyribose in DNA) and a phosphate group that is associated with carbon 5 of the sugar.

The backbone consists of alternating sugars and phosphates.

In DNA, the two strands are antiparallel: Looking at one end, one strand ends with a free carbon 5 of the deoxyribose, the other with a carbon 3 of the deoxyribose.

The two strands are held together by the attractions formed by nitrogenous bases in the center of the double-stranded molecule.

The attractions are hydrogen bonds that form due to partial positive and negative charges, as described in Chapter 2.

Most RNA molecules consist of only a single polynucleotide chain.

The uniqueness of a nucleic acid resides in its base sequence

The main principle is complementary base pairing by hydrogen bond formation.

Only four different DNA bases are found in DNA.

They are adenine (A), cytosine (C), guanine (G), and thymine (T).

Where an A is found on one strand, a T is found at the same point in the complementary strand.

Wherever a G is found on one strand, a C is found on the other.

It is between these bases that hydrogen bonds form, linking the two complementary strands.

DNA complementary strands form a double helix, a molecule with a right-hand twist.

DNA is an information molecule and serves no other purpose. The information is stored in the order of the four different bases.

This order is transferred to RNA molecules, which are used to direct the order of the amino acids in proteins.

There are three main structural differences between DNA and RNA:

                  RNA has ribose, which has oxygen at carbon 2 of the sugar.

                  Instead of having thymine, RNA molecules have uracil.

                  RNA is single-stranded.

RNA is crucial for information storage and transmission, but unlike DNA, some RNA molecules may have another function: RNA polymers with enzymatic activity similar to proteins have been discovered. These RNA molecules are called ribozymes.

DNA molecules have a much more uniform shape than the proteins they code for. The uniform shape of DNA molecules makes it easy to “read” the information they contain. This information is used to make a multitude of proteins, whose functions are related to their diverse shapes.

Lipids: Water-Insoluble Molecules.

Life is cellular; the differences between what is outside and inside a cell define life.

Biological molecules called lipids maintain these differences.

Lipids are diverse biological molecules that share a common chemical property: They are insoluble in water.  This insolubility results from the many nonpolar covalent bonds of hydrogen and carbon in lipids.

Lipids aggregate away from water, which is polar, and attract to each other via weak, but additive, van der Waals forces.

The roles for lipids in organisms include energy storage (fats and oils), cell membranes (phospholipids), capture of light energy (carotinoids), hormones and vitamins (steroids and modified fatty acids), thermal insulation, electrical insulation of nerves, and water repellency (waxes and oils).

Fats and oils store energy

Fats and oils are triglycerides, or simple lipids composed of three fatty acid molecules and one glycerol molecule. (See Figure 3.19.)

Glycerol (or glycerin) is a three-carbon molecule with three hydroxyl (—OH) groups, one for each carbon.

Each —OH is the site where an enzyme adds a fatty acid.

Fatty acids are long linear chains of hydrocarbons with a carboxyl group (—COOH) at one end. (See Figure 3.19.)

In saturated fatty acids, the hydrocarbon chain has only single carbon-to-carbon bonds. Hydrogen atoms complete the valence requirements, thus saturating the chain.

Saturated fatty acids are rigid and straight, and they are solid or semisolid at room temperature. (See Figure 3.20a.)

Animal fats are saturated.

Unsaturated fatty acids are those that have at least one double-bonded carbon in one of the hydrocarbon chains. At these positions, there are two fewer hydrogen atoms—the chain is not completely saturated with hydrogen atoms.

The double bonds in unsaturated fatty acids cause rigid kinks that prevent easy packing. As a result, unsaturated fatty acids are liquid at room temperature. (See Figure 3.20b.)

Plants commonly have short and/or unsaturated fatty acids that tend to be more fluid than animal fats, even at cold temperatures.

Fats and oils are marvelous storehouses for energy, used by animals and plants for fuel compounds in metabolism.

Phospholipids form the core of biological membranes

Lipids do not normally interact with water or with the many biologically important substances that are soluble in water.  Thus lipids play a crucial role in living cells: separating regions with different concentrations of ions and other chemicals.

Phospholipids have two hydrophobic (“water-hating”) fatty acid tails and one hydrophilic (“water-loving”) phosphate attached to the glycerol. (See Figure 3.21.)  As a result of this structure, phospholipids orient themselves so that the phosphate group faces water and the tail faces away.

In aqueous environments, these lipids form bilayers, heads facing outward, tails facing inward. (See Figure 3.22.)  Cell membranes are structured this way.

Carotenoids and steroids

Carotenoids and steroids are specialized lipids with chemical structures that are very different from those of triglycerides and phospholipids.  They are all derivatives of a simple molecule, isoprene, polymerized into chains.

Carotenoids trap light energy.

Carotenoids are light-absorbing pigments found in plants and animals.

One, beta-carotene, is a plant pigment used to trap light in photosynthesis. In animals, this pigment—when broken into two identical pieces of vitamin A—is required for vision.

Steroids are signaling molecules.

Steroids are organic compounds with a series of fused rings. (See Figure 3.24.)

Cholesterol is an example. It is a common part of animal cell membranes.

Cholesterol is absorbed from food and synthesized in the liver.

In addition to being a membrane constituent, it also is an initial substrate for synthesis of the hormones testosterone and estrogen.

Some lipids are vitamins

Vitamins are small organic molecules essential to health.

Vitamin A, for example, is made from beta-carotene. It is important for normal development, maintenance of cells, and night vision. (See Figure 3.23.)

Vitamin D is important for absorption of calcium in the intestines.

Vitamin E is an antioxidant. It protects membranes.

Vitamin K is a component required for normal blood clotting.

Wax coatings repel water

Waxes are highly nonpolar molecules. They protect our hair, birds’ feathers, and insects' eggs from both the damaging effects of excess water, and the damaging effects of water loss.

Waxes are saturated long fatty acids bonded to long fatty alcohols via an ester linkage.

A fatty alcohol is similar to a fatty acid except the last carbon has a hydroxyl group (—OH) instead of a carboxyl group (—COOH).