1. Introduction, Review of Biomolecules Lecture 1, Medical Biochemistry

2. Lecture 1 Outline Review some basic chemical nomenclature and concepts Review the structural and functional features of different biomolecules Discuss the human genome project and the future of molecular medicine

3. Common Functional Groups

4. Common Condensation Reactions

5. Common Enzymatic Conversions Oxidation-Reduction PhosphorylationPhosphatase

6. Terms/Concepts to Review Hydrophobicity and hydrophilicity Aromatic and aliphatic Ionic, or electrostatic, interactions Hydrogen bonds van der Waals interactions Covalent bonds

7. Major Causes of Disease (from Table 1.1 in text) Physical Agents: mechanical trauma, temperature extremes, radiation, electric shock Chemical Agents: toxic compounds, drugs Biologic Agents: viruses, bacteria, fungi, parasites, biochemistry professors Genetic Disease Oxygen Lack: loss of blood, decreased oxygen-carrying capacity of blood, mitochondrial poisoning

8. Disease Causes (cont.) Immunologic Reactions: anaphylaxis, autoimmune disorders Nutritional Imbalances: deficiencies, excesses Endocrine Imbalances: hormonal deficiencies/excesses

9. Two-Way Street: Medicine and Biochemistry

10. Sugars/Carbohydrates

11. Membrane Lipids

12. Sterols

13. Fatty Acids Saturated and Unsaturated

14. Which Compound Would be Found in a Membrane?

15. Nucleic Acids: Components of RNA and DNA

16. DNA: double helix

17. Adenosine Triphosphate - ATP

18. Amino Acids: Protein Building Blocks

19. Levels of Protein Structure

20. Human Genome Project A rough draft is complete, >90% sequenced Represents approximately 75,000 human genes (estimated range: 30,000 to 120,000) Based on the DNA from six individuals; thus provides little information regarding genetic diversity within the population Estimated that 95% of our DNA content is not important; represents evolutionary “baggage” Highlights the need for continued sequencing of genomes from other organisms to identify essential genes and their functions

21. Proteomics Proteomics – the study of how all proteins interact with each other in a cell Estimate 50,000 to 2,000,000 human proteins The amino acid sequence of a protein can be determined from the gene sequence, but in most cases, this cannot be used to predict overall 3D- structure or function; usually this is done by X- ray crystallography Only about 1% of proteins have had their 3D structures determined

22. The Next 40 years in Medicine Predictions made by Francis Collins M.D./Ph.D., director of the National Human Genome Research Institute

23. Predictions - 2010 Primary care providers will practice genetic medicine Preimplantation diagnoses of fertilized embryos will be widely available Gene therapy will be routinely used for a few conditions

24. Predictions - 2020 Gene-based designer drugs will be marketed for some diseases Cancer therapies will target the molecular fingerprint of each tumor type Drug susceptibility will be determined before a prescription is written Genomic intervention via homologous recombination will be used to insert genes without interfering with neighboring genes

25. Predictions - 2030 Human aging genes will be fully catalogued; clinical trials designed to increase life span will be initiated Computer models of human cells will be available for research Complete genome sequencing will cost less than $1,000 per person

26. Predictions - 2040 Comprehensive genomics-based healthcare will be standard. Individualized preventive treatments will be available and effective. Gene therapies and gene-based drug therapies will be available for most diseases. Newborn testing for disease pre-disposition in adulthood will be feasible. The average lifespan will reach 90 yrs.