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MCB63X: PRINCIPLES OF BIOCHEMISTRY

Course Instructors

Alain Viel, Rachelle Gaudet

Course Description

Principles of Biochemistry integrates an introduction to the structure of macromolecules and a biochemical approach to cellular function. Topics addressing protein function will include enzyme kinetics, the characterization of major metabolic pathways and their interconnection into tightly regulated networks, and the manipulation of enzymes and pathways with mutations or drugs. An exploration of simple cells (red blood cells) to more complex tissues (muscle and liver) is used as a framework to discuss the progression in metabolic complexity. Students will also develop problem solving and analytical skills that are more generally applicable to the life sciences.

In this updated version of the course, learners will also explore how alteration of these metabolic pathways relates to the development and progression of some human diseases.

Research

HarvardX pursues the science of learning. When you participate in this course, you will also participate in research about learning. Read our research statement to learn more.

Recommended Texts and Software

There is no required textbook. You may find this textbook, freely available from the NCBI, to be a useful resource. You can use the book by searching for the topic of interest.

Course Structure

This is a self-paced course.

Grading

There are 2 different graded components of the course:

    1. End of session (EOS) assessments. These occur after each topic and are worth a total of 50% of your grade.
    2. End of unit (EOU) assessments. These occur at the end of each unit are worth a total of 50% of your grade.

Assessments are not timed. You may leave in the middle of an assessment and come back later to complete it. All assessments are due by the close of the course run (November 24, 2020).

All other components of the course (such as PyMOL exercises) are not for credit.

Certification

You must sign up for a Verified Certificate in order to be eligible to earn a certificate.

If you achieve a cumulative score of 70% or greater (out of 100) and sign up for a Verified Certificate before the deadline, you will receive a certificate for the course. When you reach this point, you will see a "Request Certificate" option appear on the Progress page!

COURSE OUTLINE

UNIT 0: PRELIMINARIES

UNIT 1: INTRODUCTION TO BIOCHEMISTRY

1.1: Introduction

Objectives: Students should be able to

      • Explain how the chemical properties of carbon explain the structural diversity of organic molecules
      • Predict the evolution of a biochemical reaction
      • Determine the factors driving the equilibrium, directionality and spontaneity of biochemical reactions
      • Understand how matter and energy flow between living systems
      • Learn the classification of living organisms based on their abilities to extract and transform external sources of energy into usable chemical energy

End of session assessment: Introduction

End of Unit 1 Assessment

UNIT 2: STRUCTURAL BIOCHEMISTRY

2.1: Protein Structure

2.2: Protein Folding

Objectives: Students should be able to

      • Draw the chemical structure of each of the 20 natural amino acids
      • Describe the three basic building blocks of protein structure (α-helix, β-sheet and loop)
      • Describe the forces and interactions that promote protein folding
      • Evaluate, based on their knowledge of protein structure, whether a given protein structure model is likely to represent a native physiological protein structure.
      • Make predictions about the effect of mutations on protein structure and folding

End of session assessment: Protein structure and folding

Learning PyMOL *optional and ungraded!*

Objectives: Students should be able to

      • Understand the purposes of different representations of protein structures
      • Use PyMOL to navigate and illustrate protein structures

2.3: Enzyme Catalysis

2.4: Enzyme Kinetics

Objectives: Students should be able to

      • Explain how the interaction between enzyme and substrate affect the velocity of a reaction
      • Apply the fundamental principles of Michaelis-Menten enzyme kinetics
      • Predict the mode of action and the impact of different classes of inhibitors on enzyme kinetics
      • Understand the kinetics of enzymes acting on several substrates
      • Design mutations hypothesized to affect different enzyme kinetic parameters

End of session assessment: Enzymes

2.5: Lipid structure and membrane assembly

Objectives: Students should be able to

      • Explain the assembly of fatty acids into structural lipids
      • Describe the chemical and physical properties of lipids and how they lead to the assembly of biological membranes
      • Make predictions about the impact of changes in lipid structure and composition on properties of membranes
      • Describe the types of interactions between proteins and membranes
      • Summarize the roles of membrane-associated proteins on membrane properties

End of session assessment: Lipids

2.6: Carbohydrate structure

Objectives: Students should be able to

      • Recall the classification and the structure of monosaccharides
      • Explain the structural reason behind the central role of glucose
      • Understand how the chemical structure of monosaccharide leads to the formation of complex and branched carbohydrates
      • Describe structural and functional properties of extracellular carbohydrates

End of session assessment: Carbohydrates

End of Unit 2 Assessment

UNIT 3: CELLULAR BIOENERGETICS

3.1: Glycolysis

3.2: Unique features of glycolysis in red blood cells

Objectives: Students should be able to

      • Recall the steps of ATP synthesis by glycolysis
      • Explain the contribution of fermentation to glycolysis
      • Describe how glycolytic intermediates impact oxygen binding, and protect red blood cells against reactive oxygen species

End of session assessment: Glycolysis

3.3: Bacterial energetics

Objectives: Students should be able to

      • Predict the biochemical impact of linear and branched fermentation pathways
      • Explain the metabolic switches in bacteria exposed to changes in their environments
      • Contrast and compare aerobic and anaerobic respiration
      • Correlate the complexity of the human microbiota and human health

End of session assessment: Bacterial energetics

3.4: The citric acid cycle

3.5: Electron transport

3.6: ATP synthesis

Objectives: Students should be able to

      • Describe the production of reduced electron carrier during the citric acid cycle
      • Describe each steps of the production of ATP by oxidative phosphorylation
      • Correlate the number of ATP molecules produced with the point of entry of electrons in the electron transport chain
      • To compare the yield of ATP synthesis by substrate level phosphorylation and oxidative phosphorylation

End of session assessment: Oxidative phosphorylation

3.7: Regulation of glycolysis in liver cells

3.8: Regulation of blood sugar by the liver

Objectives: Students should be able to

      • Explain the role of allosteric enzymes as valves controlling the flux of intermediates in a pathway
      • Determine how transient covalent modification affects enzymes controlling key steps in metabolic pathways
      • Explain the hormonal regulation of metabolic pathways
      • Predict how changes in blood glucose level affect the biochemical and hormonal regulations of metabolic pathways including glycolysis, gluconeogenesis, glycogen synthesis and, glycogen degradation

End of session assessment: Regulation by the liver

End of Unit 3 Assessment

UNIT 4: TISSUE-SPECIFIC METABOLISM

4.1: Liver metabolism

Objectives: Students should be able to

      • Identify the major energetic pathways operating in human cells
      • Describe the response of the liver to metabolic perturbations
      • Recall the physiological changes that occur during fasting and starvation

End of session assessment: Liver metabolism

4.2: Brain metabolism

Objectives: Students should be able to

      • Identify the primary metabolic regulatory hormones that operate in humans, and their main functions
      • Describe why the brain is metabolically different from many other tissue
      • Explain the response of the brain to hypoglycemia and hypoxia

End of session assessment: Brain metabolism

4.3: Muscle metabolism

Objectives: Students should be able to

      • Describe the metabolic adaptations of muscle that enable it to rapidly generate ATP for mobility
      • Differentiate between metabolism in cardiac and skeletal muscle
      • Recall how the body and muscle adapt to physical challenges of different durations

End of session assessment: Muscle metabolism

End of Unit 4 Assessment

UNIT 5: SYNTHESIS AND DEGRADATION OF BIOMOLECULES

5.1: Nucleic acid metabolism

Objectives: Students should be able to

      • Compare the synthesis of purines and pyrimidines
      • Compare the recycling and degradation pathway of nucleotides
      • Recall the different steps of the urea cycle
      • Describe the metabolic basis and treatment of gout

End of session assessment: Nucleic acid metabolism

5.2: Carbohydrate metabolism

Objectives: Students should be able to

      • Describe the processing of complex and simple dietary carbohydrates
      • Compare the biochemical transformations of the simple sugars feeding the glycolytic pathway
      • Recall the different steps of the pentose phosphate pathway and its role

End of session assessment: Carbohydrate metabolism

5.3: Fatty acid metabolism

Objectives: Students should be able to

      • Demonstrate how fatty acid synthase catalysis leads to the production of fatty acids with an even number of carbons
      • Predict the energy inputs and energy yield of fatty acid anabolism and catabolism
      • Relate genetic deficiencies in fatty acid metabolism to human diseases

End of session assessment: Fatty acid metabolism

5.4: Cancer and metabolism

Objectives: Students should be able to

    • Describe the relationships between metabolic and cell signaling pathways in cancer pathogenesis
    • Describe the role of redox balance in cell proliferation
    • Describe how Positron Emission Tomography (PET) works

End of session assessment: Cancer and metabolism

End of Unit 5 Assessment