Introduction, Review of Biomolecules

Lecture 1, Medical Biochemistry

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

Common Functional Groups

Common Condensation Reactions

Common Enzymatic Conversions

Oxidation-Reduction Phosphorylation Phosphatase

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

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

Disease Causes (cont.)

Immunologic Reactions: anaphylaxis, autoimmune disorders Nutritional Imbalances: deficiencies, excesses Endocrine Imbalances: hormonal deficiencies/excesses

Two-Way Street: Medicine and Biochemistry

Sugars/Carbohydrates

Membrane Lipids

Sterols

Fatty Acids Saturated and Unsaturated

Which Compound Would be Found in a Membrane?

Nucleic Acids: Components of RNA and DNA

DNA: double helix

Adenosine Triphosphate - ATP

Amino Acids: Protein Building Blocks

Levels of Protein Structure

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

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 3Dstructure or function; usually this is done by Xray crystallography Only about 1% of proteins have had their 3D structures determined

The Next 40 years in Medicine

Predictions made by Francis Collins M.D./Ph.D., director of the National Human Genome Research Institute

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

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

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

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.