MEDICAL BIOCHEMISTRY

SIU School of Medicine BIOCHEMISTRY pH and Structural Biology Faculty: J.W. Shriver Problem Unit 1 - Page 1 MEDICAL BIOCHEMISTRY Problem Unit One 1999/2000 pH and … … Structural Biology Module 1: Acid/Base Properties of Biomolecules Module 2: Amino Acids, Peptides, and Proteins Module 3: Structural Biology and Disease SIU School of Medicine BIOCHEMISTRY pH and Structural Biology Faculty: J.W. Shriver Problem Unit 1 - Page 2 Faculty: Dr. John W. Shriver Department of Biochemistry and …
Module 1: Acid/Base Chemistry of Biomolecules INTRODUCTION: Water makes up about 70% of a typical cell by weight. It is one of two solvents in which most of biochemistry occurs, the second being the lipids of membranes. Water is a very unusual substance and plays a central role in defining life as we know it. Its large dipole moment means that it is a highly polar liquid (at 37°C) and thus serves as an excellent solvent for other polar (and hydrophilic ) molecules. A po- lar molecules are not easily dissolved in water and are referred to as hydrophobic. Hydrophobic molecules are excluded from an aqueous environment because they cannot interact well with water and therefore lead to a structuring of water in their vicinity (an unfavorable process). Since hydrophobes generally mix well, they separate to minimize their interface with water and form a second distinct environment - the greasy, oily environment of lipids ( lipophilic ). The biochemical system can be viewed as two different environments: the aqueous, polar environment (e.g. cytoplasm); and the hydrophobic, or lipophilic, non-aqueous environment (e.g. membranes). Hydrophobic compounds are uncharged, nonpolar species and generally contain largely aliphatic and aromatic organic groups. Hydrophilic compounds are polar and include sugars, salts, acids and bases, and polar organic groups such as amino, carboxyl, and alcohol groups. Many molecules become charged (i.e. they become ions ) when dissolved in water. Most notable of these are the acids and bases. Positive ions are referred to as cations, and negative ions are anions. The predominant cations in blood plasma is Na + (making up about 150 meq/L out of a total of 170). The predominant anions are Cl - and bicarbonate (HCO 3 - ). In contrast the predominant cations in cytoplasm are K + and Mg ++ , and the anions are inorganic and organic phosphates and negatively charged proteins. Acids and bases become charged in water through release or acceptance of a proton. Acid/base balance in a living organism is critical since it defines the relative charge on many molecules including proteins important in cellular function. In many clinical situations, acid/base balance must be modified and controlled by the physician to ensure the health of a patient. Many of the properties of proteins and other biomolecules have their origin in the acidic and basic character of functional groups on the biomolecule. Common biological phenomenon, as well as experimental techniques used in both clinical and research laboratories, make use of the acid/ base properties of biomolecules. These include such common techniques such as ion exchange chromatography and electrophoresis. The establishment and maintenance of pH gradients in membranes, and the partitioning and compartmentation of biomolecules and drugs in cells and subcellular particles are at least in part dependent on the acid/base properties of the molecules that are involved. In order to understand the function of these molecules, it would be best to obtain a working knowledge of pH and proton dissociation. Several concepts and terms must be understood at a level sufficient to work problems that require calculating for example, pH, conjugate acid, conjugate base concentrations, pK a , isoelectric points, and buffering capacity. OBJECTIVES: You will need to understand pH, H + ion concentration, the Hender- son-Hasselbalch equation, K a , pK a , ionization, protonation-deprotonation, and conjugate acid and conjugate base. An understanding of chemical equilibria will be required. Examples of the types of questions…
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