I CNG AMINO ACID

Nguyn Phc Long

Thuc tnh ha hc t nhin ca amino acid

Tt c peptide v polypeptide u c to nn t qu trnh trng hp -amino acid. Trong , c 20 -amino acid tham gia tng hp nn cc protein ca con ngi. Mt vi amino acid khc cng tn ti trong c th dng t do hay hp cht nhng khng to thnh peptide hay protein. Cc amino acid khng to protein ny c nhng chc nng rt c bit, v d nhin l cc amino acid thit yu cng c kh nng ny. V d, tyrosine c trong thnh phn hormone tuyn gip, glutamate l mt cht dn truyn thn kinh,

Hnh 6.1: Cng thc phn t ca Alanine, Glutamine, Phenylalanine Cc -amino acid trong peptide hay protein (ngoi tr proline) c mt nhm COOH v mt nhm NH2, hai nhm chc ny cng nh vo mt nguyn t carbon bt i xng c cu trc t din, hay cn gi l C. Ngoi ra, mi amino acid u c mt gc R ring bit, chng cng nh vo C(ngoi l i vi glycine, gc R ca n l mt nguyn t Hydro).

Hnh 6.2: Cu trc hai hnh th tn ti ca glycine trng thi kh. Lu kh nng quay ca nguyn t nguyn t carbone. Nhng nm gn y, Joseph Krzycki v ng nghip ca mnh i hc Ohio khm ph ra mt dn xut ca lysine l pyrrolysine trong mt s loi sinh vt c, (archaeal species) nh

Methanosarcina barkeri chng hn. Pyrrolysine v selenocysteine u c tm thy trong cu trc t nhin ca protein nh vo hot ng ca cc phn t RNA p ng c bit. Chnh s hin din 2 amino acid ny trong mt s protein khin cho cc nh khoa hc thc mc, liu hc thuyt v protein ca chng ta hon chnh cha, v c bao nhiu loi amino acid khc na c th hin din trong protein m chng ta cha pht hin c?

Phn loi cc amino acid

Ngi ta da vo gc R phn loi cc amino acid. Nu phn chia da vo tnh cht ca gc R th ta c hai nhm amino acid, l nhm a nc v nhm k nc. Nhm amino acid k nc khng hoc kh tan trong nc, do vy phn ln cc amino acid ny s nm phn ni (interior) ca protein. Nhm amino acid ny khng ion ha cng nh hnh thnh lin kt hydro. Nhm amino acid a nc c lin kt cht ch vi mi trng nc v thng to lin kt hydro vi mi trng v gia cc amino acid vi nhau. Do tnh cht c bit nh vy, cc amino acid a nc tn ti m mt ngoi ca amino acid hay trong trung tm phn ng ca cc enzyme.

Hnh 6.3: Cch nh ch ci Hy Lp i vi cc amino acid.

Lin kt peptide
Lin kt peptide c hnh thnh t phn ng polymer ha amino acid to thnh peptide v protein c dng R-CO-NH-R. Mt s hormone hay neurotransmitter, khng sinh v tc nhn chng u (antitumor agents) c bn cht l peptide mt chui ngn gm mt s amino acid.

Hnh 6.4: M t s hnh thnh lin kt peptide( trn), mt tetrapeptide (hnh gia) v dng cng hng ca n hnh di.

Nhm chc -COOH v -NH2 ca amino acid c kh nng ion ha. Trong dung dch nc, hai nhm ny tn ti di dng c biu din theo phng trnh v d di y:

Trng hp glycine trn, c Ka l 1,6 x 10-10 v do vy ta cng tnh c Kb ca n khi bit Ka x Kb = 10-14 trong dung dch nc. Lu , hng s acid Ka ca glycine l lc acid ca ion NH3+ v Kb l hng s base ca ion COO-.

Hnh 6.5: ng cong chun ca enzyme ribonuclease A ti 25oC. Nng ca KCl l 0.01M (ng mu xanh dng), 0.03M (ng mu ) v 0.15M (ng mu xanh l cy). Ti iu kin sinh l c th, pH = 7,39, nhm carboxyl s tn ti dng anion cn nhm amine s c proton ha tr thnh dng cation. Ngoi ra, amino acid c gc R khng phn

cc cng tn ti dng trung ha pH ny. Do vy, amino acid gi l cht lng cc (zwitterion): C nhit nng chy cao v b phn hy. Khng bay hi.

Mi amino acid s c mt hng s acid ring ca mnh, thng c vit di dng Ka hay pKa. Tng i s in tch ca mi amino acid, peptide hay protein s ph thuc vo pH ca mi trng xung quanh, v n c trng cho tng loi nn thng c dng xc nh chng bng phng php in di. im pH m tng i s in tch ca amino acid bng 0 ngi ta gi l im ng in (isoelectric poitn, pl)

Hnh 6.6: Minh ha cc trng hp ca hin tng to lp trng thi ion ca cc cht lng cc. Lu anode l cc dng, catode l cc m.

Nu dung dch kim mnh ta s c nng II > III, amino acid s dch chuyn v pha anod. Nu dung dch l acid mnh th nng III > II, amino acid dch chuyn v catod. Nu nng II v III bng nhau th khng c s dch chuyn no v hai cc ca in trng, ha tan nh nht. (Hay thng hiu l tng in tch bng 0)

im ng in ca cc amino acid n gin c th tnh theo cng thc sau:

Hnh 6.7: M t ng cong chun ca glycine

Trong cc trng hp phc tp, v d trong trng hp ca acid aspartic, ta phi vit cc qu trnh cn bng ca n nh hnh di y xc nh im trung ha in ca n l cn bng no ri mi p dng cng thc trn:

im trung ha in ca n nm gia cn bng (1) v (2), do vy im ng in c tnh nh sau:

Hnh 6.8: im ng in ca mt s amino acid.

Hnh 6.9: Minh ha s thay i in tch theo pH ca Glutamate v Lysine theo chiu tng dn ca nng [OH-].

 ngha chc nng ca gc R

Hnh 6.10: Kh nng to lin kt disulfide ca cysteine to thnh cystine. Gc R quyt nh tnh cht v vai tr ca bt k amino acid no. Cc amino acid khng phn cc s cu thnh nn li ca protein v c bo v khi mi trng nc bn ngoi. Ngc li, cc amino acid phn cc s to nn phn v v trung tm phn ng ca cc phn t protein c hot tnh xc tc. Vng imidazole ca histamine l mt v d. N c th ng vai tr l cht cho hay nhn proton pH sinh l, v l do ny m n thng xut hin ti vng hot ng ca cc enzyme. Mt trong nhng kh nng c bit khc na ca histamine l tr thnh cht m pH trong hemoglobin (H+ n t s phn ly ca carbonic acid), nh vy m hemoglobin c th m bo c chng nng trao i kh ca mnh. Hay nhm OH ca serine v theronine cng nh nhm SH ca cysteine khin cho cc amino acid ny c th ng vai tr l cht i nhn (nucleophiles) trong qu trnh xc tc. Nhm SH ca cysteine cn c kh nng to cu ni -S-S- vi phn t cysteine khc, to nn vng lin kt ph c vai tr quan trng trong vic nh hnh cu trc khung cng nh cu trc vng hot ng ca protein, nh th th ca insulin chng hn.

Hnh 6.11: Mt s chui peptide quan trng trong c th. Thuc tnh quang hc ca amino acid

Hnh 6.12: Thit b v nguyn l quay cc ca cc ng phn i quang (chiral) ni chung. Nguyn t carbon c 4 nhm lin kt khc nhau to thnh hnh t din c gi l mt ng phnchiral. Trong cc amino acid thit yu, ch c glycine khng phi l mt ng phn chiral v n c 2 nguyn t hydro trong phn t (phm iu kin 4 nhm khc nhau). ng phn chiral c kh nng c bit l xoay mt phng nh sng lch sang phi (dextrorotatory) hoc sang tri (levorotatory). Tt c cc amino acid trong protein ca c th u c cu hnh

thuc h L-glyceraldehyde (ngha l thuc h xoay tri). V vy chng l cc L-amino acid. Cc D-amino acid tn ti trong t nhin nhng khng c trong cu trc ca protein, c khi c tm thy trong cc khng nhm khng sinh polypeptide. Ngoi danh php D&L, ngi ta cng s dng danh php R&S (rectus & sinister), tuy t gp hn v thng c s dng trong phn t c nhiu nguyn t Carbon i quang. Lu l khng phi tt c cc ng phn L u l ng phn S v ngc li, khng phi tt c ng phn D l ng phn R. Hai cch nhn nh ng phn ny khng thc s tng ng. V d, L-threonine c th gi l (2S, 3R)-threonine; L-isoleucine l (2S,3S)-isoleucine.

Hnh 6.13: (trn) Minh haL amino acid v D amino acid. (di)L-amino acid (bn tri) v L-glyceraldehyde (bn phi). Hnh biu din ng phn D-L l dng Fisher Lu l cc gc R thm (nh tryptophan) trong amino acid c kh nng hp th tia cc tm v hp thu tt nht bc sng 280nm.

Hnh 6.14: hn cp ca cc gc v nhm ha hc v cch c ng phn i quang S & R. Hnh trnly H lm chun v hn cp theo th t t NH2 n CO2- v cui cng l

CH3,c theo chiu hn cp gim dn (ngc chiu kim ng h) do vy Alanine l ng phn quang hc S. Mt im na cng ht sc quan trng l c tnh ca gc R cng quyt nh hot tnh sinh hc ca amino acid (kh nng to lin kt hydrogen, kh nng gn gc phosphate,)

Hnh 6.15: Kh nng tham gia phn ng v v tr phosphoryl ha ca 3 amino acid.