Chemistry in Focus

3rd edition Tro

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 CH 2 O, 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 CH 2 OH 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: C 2952 H 4664 O 832 S 8 Fe 4 • 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 Determine Tertiary 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