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MCB63X: Principles of Biochemistry

Course Instructors:

Alain Viel, Rachelle Gaudet

Course description:

The course 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.

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. The course materials will be available until December 2015. However, material will be released in a staggered fashion. See the outline of the units (scroll down in this document) for release dates.

Grading:

There are 3 different graded components of the course:

  1. End of video assessments. These fall after each video, and are worth 60% of your grade.
  2. End of session assessments. These are regularly spaced after a topic finishes. They are worth 40% of your grade.
  3. End of unit assessments (EUAs). These are more challenging assessments, intended to help you learn more advanced methods and the interpretation of data. There is a variable number of EUAs for each of the units 2-5. There is no EUA for unit 1! You can receive up to 3 points (out of 100) extra credit for the highest scoring EUA of each unit!

All other components of the course (PyMOL exercises, pre- and post- test) are not for credit!

Certification:

The end of video and end of session assessments total 100% credit. The EUAs are cumulatively worth 12% extra credit.

If you achieve a cumulative score of 70% or greater (out of 100), 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 AND RELEASE SCHEDULE

UNIT 0: Preliminaries (Release June 16, 2015)

UNIT 1: Introduction to Biochemistry (Release June 16, 2015)

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

UNIT 2: Structural Biochemistry (Release June 23, 2015)

Protein structure

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


Enzyme catalysis
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

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

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 assessment: Protein purification
End of unit assessment: Lipids
End of unit assessment: Carbohydrates

UNIT 3: Cellular Bioenergetics (Release July 7, 2015)

Glycolysis
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

Bacterial energetics
Objectives: Student 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

The citric acid cycle
Electron transport
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 chai
  • To compare the yield of ATP synthesis by substrate level phosphorylation and oxidative phosphorylation

End of session assessment: Oxidative phosphorylation

Regulation of glycolysis in liver cells
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 assessment: Glycolysis and the citric acid cycle
End of unit assessment: Oxidative phosphorylation
End of unit assessment: Bacterial glucose catabolism

UNIT 4: Tissue-specific metabolism (Release July 21, 2015)

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

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

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 assessment: Biochemical adaptation of tissues - Role of the liverEnd of unit assessment: Biochemical adaptation of tissues - Starvation and muscle contraction

UNIT 5: Synthesis and degradation of biomolecules (Release July 28, 2015)

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

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

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

End of unit assessment: Nucleic acid metabolism