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Biochemistry. Amino Acids and Peptides. Amino Acids. Amino acid: a compound that contains both an amino group and a carboxyl group -Amino acid : an amino acid in which the amino group is on the carbon adjacent to the carboxyl group
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Amino Acids • Amino acid: a compound that contains both an amino group and a carboxyl group • -Amino acid: an amino acid in which the amino group is on the carbon adjacent to the carboxyl group • although -amino acids are commonly written in the unionized form, they are more properly written in the zwitterion (internal salt) form
问题 • 蛋白质氨基酸的构型是什么样的？
Chirality of Amino Acids • With the exception of glycine, all protein-derived amino acids have at least one stereocenter (the -carbon) and are chiral • the vast majority of -amino acids have the L-configuration at the -carbon
Chirality of Amino Acids • Comparison of the stereochemistry of alanine and glyceraldehyde (Fischer projection formulas)
蛋白质氨基酸分类问题 • 1.蛋白质氨基酸有哪些非极性侧链基团？（5-8） • 2.蛋白质氨基酸有哪些极性侧链基团？（5-9） • 3.蛋白质氨基酸有哪些酸性侧链基团？（5-10） • 4.蛋白质氨基酸有哪些碱性侧链基团？（5-11） • 1. 在哪些蛋白质中发现以下修饰氨基酸？-羧基谷氨酸 、5-羟赖氨酸、4-羟哺氨酸、O-磷酸丝氨酸、甲状腺素？（5-13）
20 Protein-Derived AA • Note these structural features 1. All 20 are -amino acids 2. For 19 of the 20, the -amino group is primary; for proline, it is secondary 3. With the exception of glycine, the a-carbon of each is a stereocenter 4. Isoleucine and threonine contain a second stereocenter 5. The sulfhydryl group (pKa 8.3) of cysteine, the imidazole group (pKa 6.0) of histidine, and the phenolic hydroxyl (pKa 10.1) of phenylalanine are partially ionized at pH 7.0, but the ionic form is not the major form at this pH
Uncommon Amino Acids • Each example is derived from a common amino acid by the modification shown in color • hydroxylysine and hydroxyproline are found only in a few connective tissues such as collagen • thyroxine is found only in the thyroid gland
Titration of Amino Acids Figure (a) Titration of alanine with NaOH
Titration of Amino Acids Figure (b) Titration of histidine with NaOH
氨基酸解离问题 • 1.某一氨基酸的解离过程 • 1.甘氨酸的羧基和乙酸的羧基哪一种更酸？ • 2.如果甘氨酸的羧基更酸，解释为什么？ • 3.丙氨酸的氨基和丙胺的氨基哪一个更碱？ • 4.精氨酸的胍基与赖氨酸的-氨基哪一种更碱？ • 5.如果精氨酸的胍基更碱，解释为什么？ • 6.胍基和-氨基哪一种更适合作为质子受体？ • 7.三种碱性侧链中哪一种既可作为质子供体又可作为质子受体？
Acidity: -COOH Groups • The average pKa of an -carboxyl group is 2.19, which makes them considerably stronger acids than acetic acid (pKa 4.76) • the greater acidity of the amino acid carboxyl group is due to the electron-withdrawing inductive effect of the -NH3+ group
Acidity: -NH3+ groups • The average value of pKa for an -NH3+ group is 9.47, compared with a value of 10.76 for a 2° alkylammonium ion
Basicity: Guanidine Group • The side chain of arginine is a considerably stronger base than an aliphatic amine • basicity of the guanido group is attributed to the large resonance stabilization of the protonated form relative to the neutral form
Basicity: Imidazole Group • The imidazole group on the side chain of histidine is a heterocyclic aromatic amine
氨基酸解离计算问题 • 1.如何根据pKa和pH计算共轭碱/共轭酸（质子受体/质子供体）比例？ • 2.如何根据pKa和pH计算离子总电荷（净电荷）？ • 3.如何计算等电点？ • 4.如何根据等电点判断蛋白质酸碱性
Ionization vs pH • Given the value of pKa of each functional group, we can calculate the ratio of each acid to its conjugate base as a function of pH • Consider the ionization of an -COOH • writing the acid ionization constant and rearranging terms gives
Ionization vs pH • substituting the value of Ka (1 x 10-2) for the hydrogen ion concentration at pH 7.0 (1.0 x 10-7) gives • at pH 7.0, the -carboxyl group is virtually 100% in the ionized or conjugate base form, and has a net charge of -1 • we can repeat this calculation at any pH and determine the ratio of [-COO-] to [-COOH] and the net charge on the -carboxyl at that pH
Ionization vs pH • We can also calculate the ratio of acid to conjugate base for an -NH3+ group; for this calculation, assume a value 10.0 for pKa • writing the acid ionization constant and rearranging gives
Ionization vs pH • substituting values for Ka of an -NH3+ group and the hydrogen ion concentration at pH 7.0 gives • at pH 7.0, the ratio of -NH2 to -NH3 + is approximately 1 to 1000 • at this pH, an -amino group is 99.9% in the acid or protonated form and has a charge of +1
Henderson-Hasselbalch • We have calculated the ratio of acid to conjugate base for an -carboxyl group and an -amino group at pH 7.0 • We can do this for any weak acid and its conjugate base at any pH using the Henderson-Hasselbalch equation
Henderson-Hasselbalch • using the Henderson-Hasselbalch equation, we can calculate the percent of charged or uncharged form present and the net charge on serine at pH 3.0, 7.0, and 10.0
Isoelectric pH • Isoelectric pH, pI: the pH at which the majority of molecules of a compound in solution have no net charge • the pI for glycine, for example, falls midway between the pKa values for the carboxyl and amino groups • given in the following tables are isoelectric pH values for the 20 protein-derived amino acids
（作业题） • 1。 • 1）写出谷氨酸在pH由强酸性变成强碱性过程中的解离过程， • 2）在等电点时分子以何种形式存在？ • 3）计算其等电点 • 4）作滴定曲线 • 5）pH为1、3、5、7、9、12时氨基酸向电场中什么方向移动？ • 2。计算4肽Lys-Ser-Asp-Ala的pI 答案：pI=6.4
氨基酸分离纯化问题 • 1.根据氨基酸的电荷特性分离氨基酸的方法有那些？ • 2.为什么纤维素、淀粉、琼脂等都能作为氨基酸电泳的支持物？
Electrophoresis • Electrophoresis: the process of separating compounds on the basis of their electric charge • electrophoresis of amino acids can be carried out using paper, starch, agar, certain plastics, and cellulose acetate as solid supports • in paper electrophoresis, a paper strip saturated with an aqueous buffer of predetermined pH serves as a bridge between two electrode vessels
Electrophoresis（Process) • a sample of amino acids is applied as a spot (the origin) on the solid support strip • an electric potential is applied to the electrode vessels and amino acids migrate toward the electrode with charge opposite their own • molecules with a high charge density move faster than those with a low charge density • molecules at their isoelectric point remain at the origin • after separation is complete, the strip is dried and developed to make the separated amino acids visible
肽键的问题 • 1.肽键具有什么形式？（5-37） • 2.肽键具有什么样的几何形状？（5-40） • 3.写出一个三肽的结构式：Ser-Met-Asn（5-41） • 4.定义肽、二肽、多肽、蛋白质 • 5.肽类有那些生物学功能？举例说明。（5-42）
Polypeptides • In 1902, Emil Fischer proposed that proteins are long chains of amino acids joined by amide bonds to which he gave the name peptide bonds • Peptide bond: the special name given to the amide bond between the -carboxyl group of one amino acid and the -amino group of another
Peptides • peptide: the name given to a short polymer of amino acids joined by peptide bonds; they are classified by the number of amino acids in the chain • dipeptide: a molecule containing two amino acids joined by a peptide bond • tripeptide: a molecule containing three amino acids joined by peptide bonds • polypeptide: a macromolecule containing many amino acids joined by peptide bonds • protein: a biological macromolecule of molecular weight 5000 g/mol or greater, consisting of one or more polypeptide chains
Geometry of Peptide Bond • the four atoms of a peptide bond and the two alpha carbons joined to it lie in a plane with bond angles of 120° about C and N • to account for this geometry, Linus Pauling proposed that a peptide bond is most accurately represented as a hybrid of two contributing structures • the hybrid has considerable C-N double bond character and rotation about the peptide bond is restricted
Writing Peptides • By convention, peptides are written from the left, beginning with the free -NH3+ group and ending with the free -COO- group • the repeat pattern, starting from the N-terminal amino acid, is N ---> a-carbon ---> carbonyl carbon etc.
End Chapter 5（1）
