生物化学资料：第1章 氨基酸

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1、UNIT I Protein Structure and Function第一单元第一单元 蛋白质的结构和功能蛋白质的结构和功能Chapter 1 Amino Acids 第第1章章 氨基酸氨基酸 OBJECTIVE AND REQUIREMENT After learning this chapter, students should have a good mastery ofnkey conception of AAs nthe general structure & classification of AAsnAAs with nonpolar side chain and its l

2、ocation in proteins nAAs with uncharged polar side chains nAAs with acidic and basic side chains namphoteric dissociation & pI of AAsAfter learning this chapter, students should have a fair knowledge of nabbreviations and symbols for commonly occurring AAsnoptical properties of AAsAfter learning thi

3、s chapter, students should have some acquaintance withnHenderson-Hasselbalch equation and its applicationI. OVERVIEW Proteins are the most abundant & functionally diverse macromolecules in living systems. proteinsMembraneproteinsCytoplasmicproteinsContrctionAntibodiesEnzymesCellularskeletonTransport

4、ationMaking ATPReceptorsAntigensChannelsPoresStructuralThe composition of AAs in protein related tothe structure & function of protein. II. STRUCTURE OF THE AMINO ACIDS300 different AAs in nature,only 20 found as constituents of mammalian proteins(coded)General structure, Differ in side chain (R gro

5、up), only the L isomer in proteins(human)Monomeric building blocks of proteins joined by covalent bond (peptide bond)rare AAs(hydroxyl-Pro,methyl-His,pyrro-Lys)General structureStereoisomerUn-ionized formzwitterionGeneral structureStereoisomerUn-ionized formzwitterionFree amino acid(protonated form)

6、 One exception to the general structure of amino acids is Pro, which has a imino group( -imino acid). Amino acids combined in peptide linkages The amino, carboxyl & C make up the backbone of Pr chains Monomeric building blocks of proteins joined by covalent bond (peptide bond)Peptide bondIt is usefu

7、l to classify the AAs according to the properties of their side chains. uncharged polar nonpolar acidic basic II-A. Amino acids with nonpolar side chains 9 AAs in total: Gly(G),Ala(A),Val(V),Leu(L), Ile(I),Phe(F),Trp(W),Met(M),Pro(P) Their R groups cant bind or give off H+ or participate in H- or io

8、nic bonds They can promote hydrophobic interactions. Glycine, Gly, G The smallest AAThe simplest structureC: un-chiral Alanine, Ala, AChemically unreactiveHydrophobicValine, Val, VChemically unreactiveHydrophobicbranchedessentialLeucine, Leu, LChemically unreactiveHydrophobicbranchedessentialIsoleuc

9、ine, Ile, IChemically unreactiveHydrophobicbranchedessentialMethionine, Met, MChemically unreactiveHydrophobic-S-CH3 -containingEssentialProline, Pro, PHydrophobicWith its aliphatic aliphatic side chain bonded back on to the amino group, it is conformationally rigid.IminopyrrolePhenylalanine, Phe, F

10、 Hydrophobic by virtue of its aromatic ringsessentialTryptophan , Trp, WHydrophobic by virtue of its aromatic ringsessentialII-A-1. Location of nonpolar AAs in proteinsWhy?What is importance?II-A-2. Proline II-B. AAs with uncharged polar side chains 6 AAs in total: Ser(S),Thr(T),Tyr(Y),Asn(N),Gln(Q)

11、, Cys(C) Their R-groups have zero net charge at neutral pH The side chains of Cys & Tyr have negative charge at alkaline pH. Ser,Thr & Tyr contain a polar hydroxyl group (H-bonds, phosphorylation) Asn & Gln contain a carbonyl group & an amide group (H-bonds),Cys contains SH(-S-S-)cystine disulfide b

12、ondII-B-2. Side chains as sites of attachment for other compoundsphosphatedGlcNAc(N-actylglucosamine)(O-actylgalactosamine)GalNAcglycatedII-C. Amino acids with acidic side chains 2 AAs in total: Asp(D) & Glu(E) Proton donors The side chains of them are fully ionized & negatively charged at physiolog

13、ical pH II-D. Amino acids with basic side chains 3 AAs in total: Arg(R),Lys(K) & His(H) -imidazole group-guanidinium group-amino group Proton acceptor The side chains of Arg & Lys are fully ionized & positively charged at physiological pH. His is weakly basic & the free state is largely uncharged at

14、 physiological pH. His-R group of a protein molecule, with a pKa of 6.06.5, is ionized within the physiological pH range(pH 68) II-E. Abbreviations & symbols for commonly occurring AAs Each AA name has an associated three-letter abbre. & a one-letter symb. The one-letter codes are determinated by th

15、e special rules.II-F. Optical properties of amino acids The C is chiral when the R group is anything other than hydrogen. All AAs but Gly are chiral molecules. HglycineCH3alanine amino acidRC+NH3COO-H The chiral molecules have 2 or more than 2 different position in space (stereoisomers or enantiomer

16、s or nonsuperimposable mirror images or D & L configuration). All chiral AAs in human protein are the L -form.D-AAs are found in some antibiotics & in plant & bacterial cell walls.L-glyceraldehyde (an L-sugar)CHOHHOCH2OHCOOHHH2NCH2OHL-serine (an L- AA)H2NCHCOOHCCH3OHHL-ThrHCNH2COOHCCH3HHOD-ThrH2NCHC

17、OOHCCH3HHOL-allo-ThrHCNH2COOHCCH3OHH D-allo-ThrThe characters of AA stereoisomers(1)the same exact chemical structures (2)the mirror images of each other (3)boiled and freezed etc. at the very same temperatures (4)react in the same way with other molecules. (5)they do everything the same, except for

18、 their optical rotation of plane-polarized light. III. ACIDIC & BASIC PROPERTIES OF AAsUn-ionized formzwitterionweakly acidicweakly basicSome AAs contain an ionizable R-groupAA zwitterions are amphoteric. An acid is a proton donor. A base is a proton acceptor. Whether they react as acids or bases, i

19、t depends on the pH of solution. There are the quantitative relationship betw. the pH of the solution & HA & A-. It is described by the Henderson-Hasselbach equation(the H-H equation).III-A. Derivation of the equationWeak acid Salt form or conjugate baseproton HA A- + H +Consider the release of a pr

20、oton by a weak acid represented by HA:By definition, the dissociation constant of the acid,Ka, is:Ka H+ A- HA (1)The larger the Ka, the stronger the acid(the most of the HA has dissociated into H+ & A- , vice versa.)pH pKa + log A-/HARearrangement of eqution(1) gives: 1/H+ 1/KaA-/HATaking the logari

21、thm of this equation gives: log 1/H+ log 1/Ka+ log A-/HA(the Henderson-Hasselbach equation)III-B. Buffer A buffer solution is a solution able to absorb a certain quantity of acid or base without undergoing a strong variation in pH. There is at least an acid-base conjugate pair in buffer solution. Ma

22、ximum buffering capacity occurs at a pH equal to the pKa, The effective buffering region is within approximately 1 pH unit of the pKa. (shown in the following Fig.) Fig.Titration Curve of acetic acidUtility of the buffer solutionThe buffer systems in human blood , e.g., plasmatic carbonates, phospha

23、tes or proteins etc. Numerouse buffers be used in laboratories , e.g., Tris-HCl buffer, Boric acid -KCl buffer, Tris-glycine buffer, etc. III-C. Titration of an amino acid AAs are the dipolar ions at the neutral pH. The carboxyl group of an amino acid can be dissoci-ated(deprotonated) in base soluti

24、on, vice versa. AA solution is titrated by using the standard solution of NaOH, HCl, respectively. There is an inflection point in the titration curve at the special pH. Titration CurvepKapI.pH=pKa + lgproton acceptor proton donorIII-C-1. Dissociation of the carboxyl groupWhere the COOH of FORM is t

25、he proton donor, & the COO- of FORM is the proton acceptor. III-C-2. Application of the H-H equation The H-H equation can be used to calculate the dissociation constant & the pH. For example, K1, the dissociation constant of the carboxyl group(-COOH) of an amino acid(Ala).K1 H+ ( is the fully proton

26、ated form of an amino acid. is the isoelectric form of an amino acid.)pH pK1 + log /Where the NH3 of FORM is the proton donor, & the NH2 of FORM is the proton acceptor. III-C-3. Dissociation of the amino group The -NH3+ is the second titratable group of Ala. Its acidity is much weaker than the -COOH

27、.The K2 of the -NH3+ much smaller than the K1 of the COOH. That is, the pK2 is larger than the pK1. Release of proton from the -NH3+ (the form ) results in the fully deprotonated form(). III-C-4. pKs of the alanineThe sequential dissociation of protons from the COOH & the -NH3+ of Ala is summarized

28、in the Fig. Each titratable group has a pKa that numerically equeal to the pH at which exactly of the protons have been removed from that group. The pKa of COOH Is pK1, & The pKa of NH3+ is pK2.III-C-5. Titration curve of the alanineIt is possible to plot the full titration curve of a weak acid by a

29、pplying the H-H equation to each dissociable acidic group. Fig. shows the change in pH that occurs during the addition of base to the fully protonated form of Ala() to produce the completely deprotonated form (). Note the following about the titration curve of AA.a. Buffer pairs: buffering pH region

30、 -COOH/-COO- around pK1 -NH3+/-NH2 around pK2b. When pH=pK equal amounts of two forms pH=pK1 Form& Form pH=pK2 Form& Formc. Isoelectric point(pI): pI is the pH at which an AA is electrically neutral. pI calculation: the neutral AAs: pI=(pK1+pK2)/2 the acidic AAs : pI=(pK1+pK2)/2 the basic AAs : pI=(

31、pK2+pK3)/2 III-C-6. Net charge of AAs at neutral pH At physiologic pH, the C of all AAs attaches a negatively charged group(-COO-) & a positively charged group(-NH3+) .the R chains of acidic & basic AAs have potentially charged groups.What is Net charge of AAs at neutral pH？ AAs are defined as ampho

32、teric or ampholytes. Whether AA acts as an acid or a base, it depends on the pH of solution.III-D. Other applications of the H-H equation Analyze how the pH of a physiologic solution responds to changes in the concentration of a weak acid &/or its “salt”. Analyze the abundance of ionic forms of acidic & basic druges. The permeability of drugs(the uncharged drugs pass through membranes more readily).IIII. CONCEPT MAPSIIIII. CHAPTER SUMMARY basic strcture of AA Classification Buffer Henderson-Hasselbalch equation Chiral or optical activityThanks!