Molecular Basis of Medicine

Total Contact Hours:

112 hours.

Course Director:

John V. Paietta, Ph.D., Associate Professor of Biochemistry & Molecular Biology

Course Description:

The goal of the Molecular Basis of Medicine course is to provide a strong foundation of understanding of the biochemical constituents of cells and the reactions and processes that they undergo. Its focus is biochemistry, molecular biology, and genetics for an in-depth understanding of the structure, organization, and function of living matter in molecular terms. Team-based learning modules highlight clinical correlations and the importance of understanding illness and disease at the molecular level.

Course Objectives & Integration with the Educational Objectives:

By the conclusion of this course, the student will demonstrate:

Note: A detailed set of objectives is given to students at the beginning of the course and presented section by section in their published lecture notes. A BRIEF summary of the objectives is presented below.

K1 A strong foundation in the following major topic areas:

• General biochemical principles: equilibrium, kinetics, bioenergetics, and pH
• Structure and function of proteins
• Structure, function, and replication of informational molecules (including aspects of human genetic disease)
• Metabolism of carbohydrates, amino acids, and lipids

K2 A fundamental grasp of general biochemical principles needed for the understanding of cellular biochemical processes, including the ability to:

• Interpret concepts of equilibrium (K'_eq, DG¡'), kinetics (e.g., law of mass action, rate constants), and bioenergetics
• Integrate principles of pH toward performing routine pH-related calculations

K3 The ability to identify the basic concepts of protein biochemistry, with emphasis on protein structure and function

• Starting with the properties of amino acids and followed by the peptide bond, protein structure is consecutively considered from the primary through quaternary levels. Included is a consideration of properties such as denaturation, as well as techniques used to study and characterize proteins (ranging from electrophoresis to mass spectroscopy).
• The student's understanding of basic concepts involved in protein structure and function is further expanded by detailed consideration of the following topics:
• Hemoglobin structure and function, including oxygen interactions
• Plasma proteins (e.g., albumin, blood-clotting proteins)
• Connective tissue and fibrous proteins (e.g., collagen)
• The coverage of proteins finishes with a detailed consideration of enzymology, leading to the capability to handle enzyme-related problem-solving situations. Included are the basic concepts of enzymology, with emphasis on kinetics, enzyme plots (e.g., V vs. S), and classes of enzyme inhibitors.

K4 The ability to relate the structure and function of informational molecules through an understanding of:

• Nucleotides and nucleotide metabolism.
• Structure and nomenclature of nucleotides
• Synthesis pathways and metabolism
• Metabolic defects
• Pharmacological use of nucleotide compounds
• Nucleotide assembly into polymers.
• Biochemical properties of single and double-stranded DNA
• DNA assembly into chromatin
• DNA modifying enzymes
• The process of DNA replication
• Biochemical macromolecules
• Enzymology
• The role of RNA in the information transfer process
• Different classeses of RNA
• Enzymology involved with RNA polymerases
• RNA splicing
• Alternative splicing
• Genetic code and protein synthesis
• The genetic code
• Transfer RNA
• Protein synthesis (initiation, elongation, termination)
• Antibiotics affecting this process
• Gene regulation
• Bacterial through human gene regulation fundamentals
• Properties of typical human genes
• Mutation and DNA repair
• Types of DNA damage
• Repair mechanisms
• Typical genomic rearrangements that occur in cells
• Recombinant DNA technology
• DNA cloning, blotting, sequencing, PCR and microarrays
• Clinical genetic tests

K5 The ability to apply the genetic basis of human diseases as related to how genes are transmitted in the population, including an understanding and appreciation of how to:

• Take an appropriate family history and construct a pedigree. Further, to take a given pedigree and determine the likeliest method of inheritance.
• Analyze the likely risk for family members for a given disorder (whether a single gene, chromosomal, or multifactorial)
• Identify the phenotypes of common genetic disorders
• Interpret how newborn screening can be used to diagnose disorders and the basis for successful treatment of biochemical disorders
• Predict principles of population genetics, with emphasis on:
• Hardy-Weinberg equilibrium
• Inbreeding and consanguinity
• Extend the basis of multifactorial inheritance and know the common disorders inherited in this manner
• Associate the genetic basis of cancer
• Illustrate diversity in genetic makeup as an important factor in preventative health care, diagnosis, and treatment. Understand the role of genetic counseling in such situations.

K6 The ability to differentiate how important biological molecules (carbohydrates, lipids and amino acids) are synthesized and function

K7 The ability to assess how energy is generated, used, and stored by the various organs of the body, emphasizing explanations of the inputs and outputs of human intermediary metabolism and the relation of metabolic regulation by hormones, feedback loops, and other mechanisms to organ systems and their demands for energy and metabolites

Consideration of each class of biological molecules begins with the basics of their structures and important properties. Students will then become familiarized with the general mechanisms for the regulation of metabolism and how amino acids, carbohydrates, and lipids feed into pathways for energy metabolism.

• Specific attention for carbohydrate sub-topics is given in the consecutive consideration of glycolysis, TCA cycle, gluconeogenesis, pentose phosphate pathway, glycogen and oxidative phosphorylation. The carbohydrate section ends with insulin signaling.
• For amino acids, both catabolism and anabolism of amino acids is considered, as well as specialized topics concerning one-carbon metabolism, aromatic amino acid derivatives, and biogenic amines. Heme biosynthesis and bilirubin are also considered in this section.
• An in-depth treatment of lipids completes the course and includes sections on lipid structures and properties, fatty acid oxidation, fatty acid synthesis, triglycerides, complex lipids, lipid transport, artheroschlerosis, and prostaglandins.
• Each major topic has a series of specific objectives. For example, with glycogen metabolism the student will demonstrate the ability to:
• Identify the structure of glycogen and the metabolic advantages of this structure
• Show how the glycogen molecule is synthesized and degraded; know the pathway and the energy involved
• Connect all the regulatory mechanisms controlling glycogen metabolism, including the control by hormones (glucagon, insulin, epinephrine)
• Analyze the net ATP needed to add a glucose monomer unit to glycogen from various glycolytic substrates (e.g., glycerol, lactate, etc.)
• A further example is the section covering complex lipids. The student will demonstrate the ability to:
• Summarize the role of glycerol-3-phosphate and dihydroxyacetone phosphate in the synthesis of phosphatidic acid to form triglycerides and glycerophospholipids
• Identify the subcellular locations of triglyceride and glycerophospholipid synthesis in cells
• Summerize the role of cAMP and hormone sensitive lipase in fat mobilization in adipose tissue
• Predict the metabolism of fats in diabetes and in the fed and fasting states, and the role of insulin and glucagon in these processes
• Contrast the differences between phosphatidylinositol synthesis and phosphatidylcholine and ethanolamine and serine synthesis
• List phosphorylated forms of phosphatidylinositol as second messengers within cells
• Associate the central role of ceramide, and precursors for its formation, in the synthesis of sphingolipids
• Describe the role of enzyme dysfunction to specific biochemical lipidosis diseases

C1 The ability to:

• Work effectively in team-based learning sessions in the course
• Read articles from the scientific literature and relate them to the analysis of a clinical problem in team learning situations (e.g., sickle cell anemia, gout, xeroderma pigmentosum, PKU, diabetes).
• Discuss in a team learning situation the biochemical foundation information related to the clinical problem under consideration
• Ask patients/families questions about aspects of their genetic conditions during lecture presentations of genetic disorders (e.g., urea cycle disorder, osteogenesis imperfecta, DNA repair defect/colon cancer)
• Give constructive feedback and evaluation of peers within their team group

P1 The ability to:

• Work professionally in team learning situations
• Complete all lecture/team learning session preparation, as well as contribute to a positive learning environment
• Demonstrate respect by formulating thoughtful questions for the patients/families giving presentations on their life experience with genetic disorders

Learning Activities:

Presentations, Team-Based Learning.

Syllabi:

• Schedule
• Course Materials

Assessment:

Three MCQ exams, Team-Based Learning.