단백질의 다양성 ( 그림 5.1) 5.1 아미노산 - 아미노산 이름 및 약어 ( 표 5.1), 표준아미노산 ( 그림 5.2), - 일반구조 ( 그림 5.3): α- 탄소원자, 곁사슬, 카르복실기, 아미노기 - 프로린은 고리모양 ( 곁사슬과 아미노질소사이 ) -pH7 에서 양쪽성 : 같은 수의 양전하와 음전하를 동시에 갖는 중성분자를 쯔비터이온 또는 양성이온이라 함 (1) 아미노산의 종류 중성의 무극성 - 방향족과 지방족 - 벤젠은 가장 간단한 방향족 탄화수소 ( 그림 5.4) - 시스테인의 술프히드릴 (-SH) 은 산화되어 이황화물형성 * 산성아미노산 - 생리적 pH 에서 산성 염기성 - 물분자에서 양성자를 받아 암모늄이온 (NH 4 + ) 가 된다 - 콜라겐내 리신은 강력한 교차결합함 - 히스티딘은 부분적으로 이온화되는 약염기로 작용 ; 완충액으로 작용

Chapter 5 Section 5.1: Section 5.1: Amino Acids Section 5.2: Section 5.2: Peptides Section 5.3: Section 5.3: Proteins Section 5.4: Section 5.4: Molecular Machines Biochemistry in Perspective Biochemistry in the Lab Amino Acids, Peptides, and Proteins Overview From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Proteins are molecular tools  They are a diverse and complex group of macromolecules Figure 5.1 Protein Diversity From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Proteins can be distinguished by the number, composition, and sequence of amino acid residues  Amino acid polymers of 50 or less are peptides; polymers greater than 50 are proteins or polypeptides  There are 20 standard amino acids From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  19 have the same general structure: central (  ) carbon, an amino group, carboxylate group, hydrogen atom, and an R group (proline is the exception)  At pH 7, the carboxyl group is in its conjugate base form (-COO - ) while the amino group is its conjugate acid form (-NH 3 + ); therefore, it is amphoteric Figure 5.3 General Structure of the  - Amino Acids From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Molecules that have both positive and negative charges on different atoms are zwitterions and have no net charge at pH 7  The R group is what gives the amino acid its unique properties From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Amino Acid Classes  Classified by their ability to interact with water  Nonpolar amino acids contain hydrocarbon groups with no charge Figure 5.2 The Standard Amino Acids From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Amino Acid Classes Continued  Polar amino acids have functional groups that can easily interact with water through hydrogen bonding  Contain a hydroxyl group (serine, threonine, and tyrosine) or amide group (asparagine) Figure 5.2 The Standard Amino Acids From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Amino Acid Classes Continued  Acidic amino acids have side chains with a carboxylate group that ionizes at physiological pH  Basic amino acids bear a positive charge at physiological pH  At physiological pH, lysine is its conjugate acid (-NH 3 + ), arginine is permanently protonated, and histidine is a weak base, because it is only partly ionized Figure 5.2 The Standard Amino Acids From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

(2) 생물학적으로 활성이 있는 아미노산 - 여러 α- 아미노산과 그 유도체는 화학전령으로 작용 ( 그림 5.5) - 다양한 분자의 전구물질 ; 뉴클레오티드, 핵산, 헴 등 - 생체대사과정의 중간물질로 작용 : 시트룰린, 오르니틴 등 ( 그림 5.6) 요소회로 (3) 단백질내의 변형된 아미노산 - 프로트롬빈에서 발견되는 칼슘 - 결합 아미노산잔기인 감마 카르복시 글루탐산 ( 그림 5.7) - 히드록실기의 인산화 ( 티로신 등 ) (4) 아미노산의 입체이성질체 -α- 탄소에 수소, 카르복실기, 아미노기, R 기 : 이 탄소를 비대칭 혹은 키랄탄소라함 - 공간상 입체이성질체 (stereoisomer)( 그림 5.8), 거울상 이성질체 (enantiomer), - 글리세르알데히드는 광학이성질체 (optical isomer) ( 그림 5.9) ; D, L 로 표기 - 단백질에서는 L- 아미노산만 존재 - 키랄성의 구조와 기능 : L- 아미노산은 우선성나선을 형성, 이들 효소는 한 거울상이성질체의 기질만을 결합 (protease 는 α- 아미노산으로 구성된 보통 단백질만 분해 )

Section 5.1: Amino Acids  Biologically Active Amino Acids  Amino acids can have other biological roles 1. Some amino acids or derivatives can act as chemical messengers  Neurotransmitters (tryptophan- derivative serotonin) and hormones (tyrosine-derivative thyroxine) Figure 5.5 Some Derivatives of Amino Acids From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids 2. Act as precursors for other molecules (nucleotides and heme) 3. Metabolic intermediates (arginine, ornithine, and citrulline in the urea cycle) Figure 5.6 Citruline and Ornithine From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Modified Amino Acids in Proteins  Some proteins have amino acids that are modified after synthesis  Serine, threonine, and tyrosine can be phosphorylated   -Carboxyglutamate (prothtrombin), 4-hydroxyproline (collagen), and 5-hydroxylysine (collagen) Figure 5.7 Modified Amino Acid Residues Found in Polypeptides From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Amino Acid Stereoisomers  Because the  -carbon (chiral carbon) is attached to four different groups, they can exist as stereoisomers  Except glycine, which is the only nonchiral standard amino acid From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  The molecules are mirror images of one another, or enantiomers  They cannot be superimposed over one another and rotate plane, polarized light in opposite directions (optical isomers) Figure 5.8 Two Enantiomers From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Molecules are designated as D or L (glyceraldehyde is the reference compound for optical isomers)  D or L is used to indicate the similarity of the arrangement of atoms around the molecule’s asymmetric carbon to the asymmetric carbon of the glyceraldehyde isomers  Chirality has a profound effect on the structure and function of proteins Figure 5.9 D- and L-Glyceraldehyde From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

(5) 아미노산의 적정 - 이온화그룹함유 ( 표 5.2) - 아미노산의 적정 시 아미노산의 구조 ( 그림 5.10a) - 알라닌은 적정 시 2 개의 양성자를 잃는다. - 등전점. 등전점구하는 식 - 이온성곁사슬을 갖는 아미노산의 적정 ( 그림 5.10b); 예 글루탐산, 히스티딘 - 문제 리포트 (6) 아미노산의 반응 * 펩티드결합형성 - 그림 펩티드결합은 매우 단단하고 동일한 평면상에 존재 ( 그림 5.12) - 아미노산의 C-N 결합이 다른 형태의 C-N 결합과 짧다 : 부분적으로 이중결합의 공명혼성임 - 펩티드의 1/3 이 자유롭게 회전불가능 - 일부분에서 R 기가 반대편에 나타남 ( 그림 5.12?) 시스테인의 산화 -SH 기가 반응성이 매우 높다 - 산화되 시스틴형성 ( 그림 5.13)

Section 5.1: Amino Acids  Titration of Amino Acids  Free amino acids contain ionizable groups  The ionic form depends on the pH  When amino acids have no net charge due to ionization of both groups, this is known as the isoelectric point (pI) and can be calculated using: pK 1 + pK 2 pI = 2 From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Alanine is a simple amino acid with two ionizable groups  Alanine loses two protons in a stepwise fashion upon titration with NaOH  Isoelectric point is reached with deprotonation of the carboxyl group Figure 5.10 Titration of Two Amino Acids: Alanine From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Amino acids with ionizable side chains have more complex titration curves  Glutamic acid is a good example, because it has a carboxyl side chain group  Glutamic acid has a +1 charge at low pH  Glutamic acid’s isoelectric point as base is added and the  - carboxyl group loses a proton  As more base is added, it loses protons to a final net charge of -2 Figure 5.10 Titration of Two Amino Acids: Glutamic Acid From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Amino Acid Reactions  Amino acids, with their carboxyl, amino, and various R groups, can undergo many chemical reactions  Peptide bond and disulfide bridge are of special interest because of the effect they have on structure Figure 5.11 Formation of a Dipeptide From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Peptide Bond Formation: polypeptides are linear polymers of amino acids linked by peptide bonds  Peptide bonds are amide linkages formed by nucleophilic acyl substitution  Dehydration reaction  Linkage of two amino acids is a dipeptide Figure 5.11 Formation of a Dipeptide From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  N-terminal amino acid has the free amino group; the C- terminal has a free carboxyl group  Amino acid sequence leads directly to the protein’s native conformation Figure 5.11 Formation of a Dipeptide From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Linus Pauling was the first to characterize the peptide bond as rigid and flat  Found that C-N bonds between two amino acids are shorter than other C-N bonds  Gives them partial double- bond characteristics (they are resonance hybrids) Figure 5.12 The Peptide Bond From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Because of the rigidity, one- third of the bonds in a polypeptide backbone cannot rotate freely  Limits the number of conformational possibilities Figure 5.12 The Peptide Bond From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Cysteine oxidation leads to a reversible disulfide bond  A disulfide bridge forms when two cysteine residues form this bond  Helps stabilize polypeptides and proteins Figure 5.13 Oxidation of Two Cysteine Molecules to Form Cystine From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press

Section 5.1: Amino Acids  Schiff Base Formation: imine products of primary amine groups interacting with carbonyl groups  Most important examples are amino acid biosynthesis reactions  Schiff bases, referred to as aldimines, are intermediates formed by the reaction of an amino group with an aldehyde group From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 Oxford University Press