Scientific Principles of Medicine
Tip #1 – Use the Learning Objectives
For example, Lecture 2 from September 30 (2014) identified the following LOs:
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Describe the regulation of gluconeogenesis and list the steps in glycolysis it bypasses to form
glucose
Describe the steps and regulation of glycogen synthesis and degradation
Understand the hormonal and metabolic adaptation to starvation
Describe the role of the pentose phosphate pathway in RBC survival along with lipid and nucleic
acid metabolism
Be able to diagnose a glycogen storage disease from a clinical scenario
Describe the metabolic pathways that become important when glucose is persistently elevated in
the plasma and their clinical significance
 STEP 1: Start with the “big picture” and work your way down to the details. For example,
looking at the second LO, I could say:
Regulation of glycogen phosphorylase is largely accomplished by phosphorylation. The addition of a
phosphate group coverts the inactive phosphylase b to an active phosphylase a. In addition, this enzyme
is also regulated allosterically. The form in the muscle is activated by AMP and inhibited by ATP. The form
of phosphorylase in the liver is inhibited by glucose. The mode of allosteric regulation tailors the overall
regulation of the enzyme to the needs of specific tissues.
Glycogen synthesis and degradation is largely controlled by the phosophorylation state of the enzymes,
with fine tuning by the allosteric signals listed above. The phosphorylation levels of proteins within the
cell are directly controlled by response to hormones.
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When there is demand from glucose protein phosphorylation occurs, signalling the release of
glucose from glycogen in the liver. Therefore the phosphorylated state of glycogen
phosphorylase must be the active form of the enzyme so that glucose is released from glycogen.
To insure that both synthetic and degradative pathways are not active at the same time we would
expect that the phosphorylated state of glycogen synthase must be inactive.
During periods of high blood sugar levels, hormonal signalling causes the storage of glucose in
glycogen by leading to dephosphorylation of enzymes in the cell. This dephosphorylation
activates glycogen synthase and inactivates glycogen phosphorylase, again insuring that only one
direction is active at a time.
(From Glycogen & Integrated Regulation available at:
https://oli.cmu.edu/jcourse/workbook/activity/page?context=c09b5b0780020ca6015536bdfb7a8b11)
 STEP 2: Identify or organize the details and other important parts of the process.
You can write out the steps, draw a diagram, or even try to recreate a diagram from lecture or
your readings. An example might be:
Glycogen regulation by phosphorylation of enzymes. Glycogen phosphorylase is active when phosphorylated. In
contrast, the phosphorylation of glycogen synthase inactivates the enzyme. Dephosphorylation leads to a reversal
in the regulation; inactivation of glycogen phosphorylase and activation of glycogen synthase.
(From Glycogen & Integrated Regulation available at:
https://oli.cmu.edu/jcourse/workbook/activity/page?context=c09b5b0780020ca6015536bdfb7a8b11)
 STEP 3: Check for understanding and elaborate. Ask yourself “Why is this important?”
and “So what?” or “Then what?” or explain how it relates/connects to another related
topic/concept.
Still using LO#2, I might say:
The coordinated regulation of glycolysis and gluconeogenesis fits perfectly with the direct hormonal
control of glycogen metabolism to insure the liver cell responds appropriately to hormonal signals. For
example, the production and release of glucose when glucagon or epinephrine are present, or the
storage and, if required, the oxidation of glucose when insulin is present.
Tip #2 – Create concept maps, flows charts, or tables to help you organize the information.
There are a lot of details and steps involved in some of the processes and pathways and giving the
information a structure and identifying key characteristics will help with long term memory and retrieval.
Table source: https://oli.cmu.edu/jcourse/workbook/activity/page?context=c09b5b0780020ca6015536bdfb7a8b11
 Once you feel comfortable with the information in the diagram, chart, or table, use Question Stems
to check your understanding and apply the knowledge.
Tip #3 –Understand the basic principles. Ensure that you truly understand the basics and are able to
describe the interactions, variations, etc. For example – consider: what happens when glucose is not available?
What role do lipids play then? What are the pathways for breaking down lipids? For making lipids?
 If you need help understanding the basic concepts, check out the tutorials for Glycolysis and
Cellular Respiration at “Hand-written Tutorials” - http://www.handwrittentutorials.com/
 Check out the Biochemistry Open + Free Course from Carnegie Mellon –
https://oli.cmu.edu/jcourse/lms/students/syllabus.do?section=c09b4f9e80020ca6009f966fedf
a5e80 - be sure to use the review questions/activities (labeled: Did I get this?)
 Animations explaining some of the processes:
https://oli.cmu.edu/jcourse/workbook/activity/page?context=c09b5b6480020ca6004d67ca28
9f3b47
 A quick overview of metabolic pathways: http://www2.ufp.pt/~pedros/bq/integration.htm
 Practice MC questions: http://umed.med.utah.edu/testfiles/topics.cfm?CID=6