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Biochemistry in USMLE Step 1
  • 17 Mar 2015

At the end of my recent post, we highlighted the importance of developing a comprehensive knowledge base. Biochemistry is a highly tested, yet often neglected basic science topic that is guaranteed to appear on the USMLE Step 1. Although preparing for biochemistry may be a daunting task because of the volume of information involved in thorough understanding, know that Step 1 does not require rote memorization of every intermediate and enzyme involved in each pathway.

We will use a schematic for heme biosynthesis as an example:

(These are notes are derived from my personal Step 1 preparation. I take no responsibility for any inaccuracies or omissions that may or may not appear in this scheme).

Although many enzymes and intermediates are listed in this scheme, it is important to note that it is unnecessary to memorize all of them! In fact, it would be very inefficient to memorize each biosynthetic pathway in preparation for the USMLE. Instead, focus on the following:
  • Rate limiting steps: It is highly recommended that examinees be familiar with the rate limiting steps in each pathway (ex: D-ALA synthase above, phosphofructokinase in glycolysis, carbamoyl phosphate synthetase in the urea cycle etc). Along these same lines, sites of regulation and regulatory molecules are high-yield topics as well.
  • Cofactors required for specific enzymes: Cofactor and vitamin deficiencies are often encountered in disease states. As an example, recall that B12 and folate are required for erythropoiesis, and that deficiencies of these molecules result in differential physical exam and lab findings.
  • Enzymes implicated in disease: This is perhaps one of the easiest aspects of biochemistry. Inborn errors of metabolism are one of the few subjects that may be tested in “one-step” questions. Knowing the single gene mutation that causes an enzyme deficiency leading to SCID, or von Gierke’s, or acute intermittent porphyria (see above) can score quick points on Step 1.
Remember to focus your preparation on the finite number of topics tested on the USMLE. Step 1 does not test clinical management (although Step 2 and 3 do), drug dosing, or trade names. For biochemistry, know rate limiting enzymes, important cofactors, and enzymes that play a role in disease pathogenesis.
  • 17 Mar 2015