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 3D-structure or function; usually this is done by X-ray 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.