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  1. Biochemistry on the Step 1 focuses on cellular processes, so reviewing the basics of cell biology provides important foundation

  2. This is an introductory chapter, so focus on understanding the layout of the cell, especially how organelles are organized and their core functions

  3. Though some topics will come up in later chapters (as noted), focus on clinical correlates: Step 1 classically tests these basic concepts through Pharmacology


  1. Cells separate their key machinery into smaller membrane-bound organelles

  2. The most important components of the cell are

    1. Plasma membrane (regulates communication with the world outside of the cell)

    2. Cytosol (signal and material transport, protein synthesis)

    3. Nucleus (houses DNA, transcription)

    4. Endoplasmic reticulum and Golgi (protein processing and transport)

    5. Mitochondria (site of energy production, other metabolic processes)

    6. Lysosome (breakdown of waste)

Figure 1-1.

Overview of cell structure.


  1. The plasma membrane is the point of contact with the outside of the cell

  2. It is made of a phospholipid bilayer that prevents cell contents from spilling out and regulates cellular intake—so it is important for Pharmacology

  3. Hydrophobic molecules can pass through the membrane freely

    1. Steroid hormones and thyroid hormone are common hydrophobic compounds that pass through the plasma membrane

  4. Hydrophilic and large molecules require protein channels or transporters to enter the cell

    1. Glucose transporters (GLUTs) respond to insulin differently depending on isoform

      • GLUT4 is insulin responsive (muscle, adipose tissue)

      • Some diabetes drugs target glucose/sodium cotransporters (SGLTs)

      • These will be reviewed in detail in Chapter 5

    2. Drugs only enter the central nervous system if they are hydrophobic due to the blood-brain barrier (BBB), composed of tightly packed cells

      • Antihistamines—first-generation drugs are nonpolar and pass through the BBB → drowsiness

      • Second generation are charged and remain peripheral → no CNS symptoms

  5. Cells can be polarized: The plasma membrane composition is different on cell

    1. Gut epithelium faces the gut lumen on one side and blood vessels on the other, so each side has unique signals and transporters

      • Lactase is only expressed on the luminal side

    2. Embryologic development also relies on polarity of cells to help develop and shape the organism


  1. The cytosol is a busy place, so it is important to focus on what specifically is relevant for Step 1

    1. How signals from outside the cell are processed in the cytosol vs. nucleus (Chapter 4)

    2. How protein synthesis is localized between cytosol and endoplasmic reticulum (Chapter 3)

    3. What parts of metabolism happen in the cytosol (Chapter 5)

    4. The structure and function of the ...

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