A drug has an easier time passing through membranes when it is not charged. This means that for weak acids like aspirin, the uncharged form (HA) can cross membranes, but the charged form (A-) cannot. Similarly, for weak bases like morphine, the uncharged form (B) can permeate the cell membrane, while the charged form (BH+) cannot. The concentration of the permeable form of each drug at the absorption site is determined by the ratio of the charged and uncharged forms, which is influenced by the pH at the site of absorption and the strength of the weak acid or base, represented by the pKa of the ionizable group. The Henderson-Hasselbalch equation is a useful tool for determining the distribution of a drug across a membrane separating two compartments with different pH levels, such as the stomach (pH 1.0–1.5) and blood plasma (pH 7.4).

Biochemistry is often seen as a collection of facts or equations to be memorized rather than a cohesive set of concepts to be understood. Providing details to enhance understanding can sometimes be distracting. What is lacking is a roadmap—a guide that helps students understand how different topics are interconnected and tell a coherent story. To address this, this textbook includes a series of biochemical concept maps that visually illustrate the relationships between ideas presented in each chapter and how the information can be organized. A concept map is a tool for visualizing the connections between concepts, arranged in a hierarchical manner, with the most general concepts at the top and the more specific concepts below. These concept maps serve as templates or guides for organizing information, enabling students to integrate new knowledge with what they already know. The process of constructing concept maps is described below.

Concepts in the biochemical maps are represented by boxes and are defined as "perceived regularities in events or objects." These concepts can include abstractions (such as free energy), processes (such as oxidative phosphorylation), and compounds (such as glucose 6-phosphate). The central idea is positioned at the top of the page, with subsequent concepts drawn in boxes beneath it. The size of the text indicates the relative importance of each idea. Lines are drawn between concept boxes to indicate relationships, with labels on the lines defining the connection between two concepts. The direction of the arrowheads on the lines indicates the direction of the connection.

Unlike linear flow charts or outlines, concept maps can include cross-links that show complex relationships between ideas represented in different parts of the map or between the map and other chapters in the book. These cross-links can identify concepts that are central to multiple topics in biochemistry, helping students apply their knowledge in clinical situations and on exams like the United States Medical Licensure Examination (USMLE) that require integration of material. By visually perceiving nonlinear relationships between facts, students can better understand the interconnectedness of concepts, as opposed to relying solely on cross-referencing within linear text.

Each amino acid contains an α-carboxyl group and a primary α-amino group, except for proline, which has a secondary amino group. At physiological pH, the α-carboxyl group dissociates, forming the negatively charged carboxylate ion (−COO−), while the α-amino group is protonated (−NH3+).
A drug passes through membranes more readily if it is uncharged. Thus, for a weak acid, such as aspirin, the uncharged HA can permeate through membranes, but A− cannot. Likewise, for a weak base, such as morphine, the uncharged B form permeates through the cell membrane, but BH+ does not. Therefore, the effective concentration of the permeable form of each drug at its absorption site is determined by the relative concentrations of the charged (impermeant) and uncharged (permeant) forms. The ratio between the two forms is determined by the pH at the site of absorption and by the strength of the weak acid or base, which is represented by the pKa of the ionizable group. The Henderson-Hasselbalch equation is useful in determining how much drug is found on either side of a membrane that separates two compartments that differ in pH, for example, the stomach (pH 1.0–1.5) and blood plasma (pH 7.4).
IV. CONCEPT MAPS
Students sometimes view biochemistry as a list of facts or equations to be memorized, rather than a body of concepts to be understood. Details provided to enrich understanding of these concepts inadvertently turn into distractions. What seems to be missing is a road map—a guide that provides the student with an understanding of how various topics fit together to “tell a story.” Therefore, in this text, a series of biochemical concept maps have been created to graphically illustrate relationships between ideas presented in a chapter and to show how the information can be grouped or organized. A concept map is, thus, a tool for visualizing the connections between concepts. Material is represented in a hierarchic fashion, with the most inclusive, most general concepts at the top of the map, and the more specific, less general concepts arranged beneath. The concept maps ideally function as templates or guides for organizing information, so the student can readily find the best ways to integrate new information into knowledge they already possess. Concept map construction is described below.
A. Concept boxes and links
Educators define concepts as “perceived regularities in events or objects.” In the biochemical maps, concepts include abstractions (for example, free energy), processes (for example, oxidative phosphorylation), and compounds (for example, glucose 6-phosphate). These broadly defined concepts are prioritized with the central idea positioned at the top of the page. The concepts that follow from this central idea are then drawn in boxes (Fig. 1.13A). The size of the type indicates the relative importance of each idea. Lines are drawn between concept boxes to show which are related. The label on the line defines the relationship between two concepts, so that it reads as a valid statement (that is, the connection creates meaning). The lines with arrowheads indicate in which direction the connection should be read (Fig. 1.14).
B. Cross-links
Unlike linear flow charts or outlines, concept maps may contain cross-links that allow the reader to visualize complex relationships between ideas represented in different parts of the map (Fig. 1.13B) or between the map and other chapters in this book (Fig. 1.13C). Cross-links can, thus, identify concepts that are central to more than one topic in biochemistry, empowering students to be effective in clinical situations and on the United States Medical Licensure Examination (USMLE) or other examinations that require integration of material. Students learn to visually perceive nonlinear relationships between facts, in contrast to cross-referencing within linear text.
V. CHAPTER SUMMARY
Each amino acid has an α-carboxyl group and a primary α-amino group (except for proline, which has a secondary amino group). At physiologic pH, the α-carboxyl group is dissociated, forming the negatively charged carboxylate ion (−COO−), and the α-amino group is protonated (−NH3+).