Chemistry in Focus 3rd editionTro

Chapter 16

Biochemistry and Biotechnology

Brown Hair, Blue Eyes, and Big Mice

• Study of the molecular blueprints that are genes has increased our understanding of how we think, how we behave, and what diseases we might develop.

• We understand not only how a molecular sequence works, but how to take it from one organism and implant it in another.

• 4 type of molecules in living organisms– Lipids– Carbohydrates– Proteins– Nucleic acids

Lipids and Fats

• Lipids are cellular components that are insoluble in water, but extractable in nonpolar solvents.– Fats, oils, fatty acids, steroids, some vitamins

• They form the structural components of biological membranes and reservoirs for long-term energy storage.

• They contain twice as much energy per gram than any other class of biochemical compounds.– Efficient energy storage

Fatty Acids

• One type of lipid

• Organic acid with a long hydrocarbon tail

• General formula RCOOH:

Triglycerides• Fats and oils are a combination of glycerol

and three fatty acids.

Tristearin

• Structure/property relationships– Long hydrocarbon chains: nonpolar,

immiscible with water– Energy is extracted via oxidation of these long

chains (as in gasoline).– Chains are saturated: efficient packing, solids– Fat is conveniently stored in the body.

• Provides thermal insulation

Triolein• Main component of olive oil

• Double bonds in R groups interferes with efficient packing, liquid at room temperature

Trilinolenin

• Polyunsaturated fat: multiple double bonds in the hydrocarbon chains– Animal fats tend to be saturated.– Plant fats tend to be unsaturated.

• Variations in structure serve different purposes in the human body.

Carbohydrates• Chemical formulas are multiples of CH2O,

carbon and water

• Function in the body as short-term energy storage

• Chemical structure related to:

• Carbohydrates are polyhydroxy aldehydes, or ketones, or their derivatives.

Glucose

• This is a dynamic system, but at any instant more molecules are in the ring form.

Glucose Properties

• Hydroxyl groups mean strong hydrogen bonding with each other and with water.

• Solubility in body fluids leads to function as a quick energy source.

• Since it is partially oxidized, it yields less energy per gram than octane or lipids.

• Balance between efficient energy storage and ease of access to that energy

Fructose

• Isomer of glucose• Two CH2OH groups mean it is more

soluble in water and sweeter.– Takes less to offer same sweetness

Saccharides• Monosaccharides – carbohydrates composed of a

single ring• Disaccharides – joined monosaccharides, double ring

structures

Complex Carbohydrates• Polysaccharides

– Most common are starch and cellulose– Subtle molecular difference (the oxygen linkage

between rings and subsequent nature of resulting hydrogen bonds) means a dramatic macroscopic result.

– Human enzymes cannot cut chains of cellulose.

Proteins

• The body CAN metabolize proteins.

• The body metabolizes proteins ONLY as a last resort.

• Proteins have much more important other work to do in the body.

Protein Functions

• Compose much of the physical structure of the body (muscle, hair, skin)

• Act as enzymes to control chemical reactions

• Act as hormones to regulate metabolic processes

• Transport oxygen from lungs to cells

• Act as antibodies

• Protein molecules are long chains of repeating units of amino acids.

– Differences among amino acids arise from different R groups.

• Changing the number and order of these amino acids changes the functionality of the protein.

• The simplest R group is the hydrogen atom, and the amino acid is glycine.

The Peptide Bond

• The acidic end of one amino acid reacts with the amine side of another to form a peptide bond.

• Two linked amino acids is called a dipeptide.

• Chains with 50 units or less are polypeptides; chains with over 50 units are called proteins.

Sickle Cell Anemia

• Hemoglobin (Hb) is a medium size protein with a molecular formula that contains close to 10,000 atoms: C2952H4664O832S8Fe4

• Replacing polar glutamate with nonpolar valine at one position, on two of these chains, lowers the solubility of Hb resulting in red blood cell deformation.

Protein Structure

• The structure of a protein is finely tuned to achieve a specific function.

• We characterize protein structure in four categories:– Primary– Secondary– Tertiary– Quaternary

Primary Structure

• The amino acid sequence held together by peptide bonds

• Abbreviations like gly-val-ala-asp are used to note the sequence of the amino acid.

Secondary Structure

• The way the amino acid chain orients itself along it axis– Alpha-helix– Pleated sheet

Alpha-Helix

• Helical shape is maintained by hydrogen bonds between different amino acids along the protein chain.

• α-keratin is an alpha-helix and is responsible for the elasticity of hair and wool.

• It works like a spring.

Pleated Sheet

• Protein forms zig-zag chains that stack neatly

• Silk is pleated sheet• Inelasticity due to full

extension of protein chains

• Softness due to sliding of sheets past each other

Tertiary and Quaternary Structure• Tertiary structure is the bending and folding due to

interactions between amino acids on the chain.– Completely extended– Globular or ball-like

• Overall shape of the particular protein strand• Arrangement of subunits of the protein chain in space

is quaternary structure.

Interactions of R Groups to DetermineTertiary and Quaternary Structure

Common Proteins: Hemoglobin• Entire structure not known until late 1950s• HB folds to hold four flat molecules called heme

groups.– Pick up oxygen at lungs– Release it at cells undergoing glucose oxidation

• Interior of Hb molecule is highly nonpolar.– Repels water– Allows oxygen in and out

• Exterior is polar– Hemoglobin is soluble in water.

α-Keratin

• Composes hair and wool

• α-helix structure maintained by hydrogen bonding

• Hair– 3 α-helices in a coil held by hydrogen bonds

(easy to change) and disulfide linkages (require chemical treatment)

Lysozyme

• Acts as an enzyme• Cleaves polysaccharide

units within cell walls– Walls explode killing the

bacteria

• In nasal mucus and tears• Discovered by Alexander

Fleming in 1922

Insulin

• Acts as a hormone• Synthesized in the

pancreas• Small (51 amino acids)• Promotes entry of glucose

into muscle and fat cells, lowering blood glucose level

• Diabetics must inject insulin.

Nucleic Acids

• The templates from which all proteins are made

• Two types– DNA (deoxyribonucleic acid)

• Occurs in cell information center

– RNA (ribonucleic acid)• Occurs throughout interior of cells

Nucleotides

Nucleotides• Phosphate and sugar groups are identical in

every nucleotide.• Four different bases

– A, adenine– T, thymine– C, cytosine– G, guanine

• Codon– A group of three bases that codes for one amino acid

• With minor exceptions, the code is universal; it is identical in all organisms, from bacteria to humans.

DNA

• Occurs in chromosomes, found in the nucleus of most cells of the human body– There are 46 in humans

• Each set of DNA contains all the DNA required to specify an entire person.– Organs make those proteins specific for their

own functioning.– But the blueprint is there for everything else

too

DNA Replication

• Mechanism elucidated by Watson, Crick, and Franklin in 1953

• Complementary base units are formed (with the help of enzymes) after the double-helix unzips.– Two daughter DNA strands formed

• Daughter DNA molecules are identical in every way to the parent.

Protein Synthesis

• Genes are sections of DNA, thousands of base pairs long.

• When the gene for a protein is needed, that section of DNA unwinds.

• A messenger RNA (mRNA) is formed, which is a complement to the unwound section.

• expression

• mRNA goes to a ribosome where protein synthesis occurs.

• Cells express only the proteins specific to their function.

Viruses• Definition lies somewhere between life and

non-life.– Difficult to kill, do not respond to antibiotics

• Require the machinery of a host cell to reproduce– Virus inserts it own DNA into the

chromosomes of the host.– Host then expresses viral DNA

• Common cold, flu, measles, polio, smallpox, ebola

AIDS

• HIV causes AIDS• HIV attacks immune system

cells, releasing its RNA.• Reverse transcriptase forms

viral DNA from the RNA• An enzyme inserts the DNA

into the chromosomes of the host cell.

• Cell dies, releasing daughter HIVs

Recombinant DNA Technology• Employs restriction enzymes which cut DNA in

specific places

• DNA pieces can be separated by gel electrophoresis.– Even single genes can be isolated.

• A DNA strand from one organism (a human) can be introduced into another (a bacterium).

• Bacterium are cultured, replicating DNA.

• This is a source for the protein coded for by that DNA.

Pharmaceuticals

• Insulin– Animal insulin is not tolerated by all diabetics.– The gene that codes for the production of

human insulin was copied and expressed by a bacteria.

– Human insulin factory– Most diabetics take genetically engineered

insulin today.

• Human growth hormone

Agriculture

• Bacteria, without the protein that accelerates ice crystal formation on crop leaves, have been engineered.

• What impacts might this (and similar technologies) have on the environment?

Genetic Screening and Disease Therapy

• Can we screen for genes that may indicate predisposition to disease?– And should insurance companies have

access to this information?

• Genetic engineering techniques might one day be used to treat genetic disease directly.– CF, Huntington’s disease, MD

CLONING

• When egg DNA is modified, whole new organisms can develop.

• Science fiction is now possible in reality.

• Embryonic cloning has been achieved in animals.

• By nuclear transfer, cloning of adult organisms has been achieved in animals.

Therapeutic Cloning and Stem Cells

• Reproductive cloning is generally viewed as unethical.• Therapeutic cloning is regarded as acceptable.

– Goal is to produce embryonic stem cells that are genetically identical to the adult donor

– These are the master cells normally present in embryos, days after the fertilization of an egg.

• Therapeutic cloning offers the potential to make stem cells that are a perfect genetic match to the donor of the DNA from whom the stem cells are cloned.– No rejection by the immune system– Fraught with controversy