Bg hoa sinh 2 phan 2 0207

Tao acid 5 - amino levulinic ALA Stf tdng hdp ALA xay ra d ty the, ndi ma succinyl CoA dtfdc tao thanh trong cac phan tfng ciia chu trinh acid citric.. Khi hemoglobin bi phan huy se giai

CHlJdNG 4

CHUYEN HOA HEMOGLOBIN

MUC TIEU

1 Trinh bay va giai thich dtfdc tien trinh va cd chd cua qua trinh sinh tdng hdp hemoglobin.

2 Trinh bay va giai thich dtfdc tien trinh va cd che ciia qua trinh thoai hda hemoglobin.

3 Neu va giai thich dtfdc nhtfng benh ly gay ra do rd'i loan chuyen hda hemoglobin.

1 SINH TONG H0P HEMOGLOBIN

1.1 Sinh tdng hcfp hem

Hem cd cau triic gdm nhan protoporphyrin III ket hdp vdi Fe"+.

Stf tdng hdp hem xay ra trong hau het te bao ngoai trtf hong cau trtfdng thanh vi khong cd ty the.

Khoang 85% stf tdng hdp hem xay ra d te bao tien hong cau trong tuy xtfdng

1.1.1 Tong hcfp nhan protoporphyrin III

Hai nguyen lieu khdi dau cho qua trinh tdng hdp nhan porphyrin ttf do tao hem la

succinyl CoA va glycin Succinyl CoA la mot cha't trung gian ciia chu trinh acid citric, con glycin

la mot acid amin Qua trinh tdng hdp nhan protoporphyrin qua cac giai doan sau:

1.1.1.1 Tao acid 5 - amino levulinic (ALA)

Stf tdng hdp ALA xay ra d ty the, ndi ma succinyl CoA dtfdc tao thanh trong cac phan

tfng ciia chu trinh acid citric Glycin dtfdc hoat hda bdi pyridoxal phosphat (vitamin B6)

Succinyl CoA ket hdp vdi glycin, loai CoA tao thanh acid a - amino -P - ceto adipic Chat nay

nhanh chdng bi khtf carboxyl de tao thanh acid 5 -amino levulinic (ALA) vdi stf xiic tac ciia

enzym ALA synthetase vdi coenzym la pyridoxal phosphat:

Acid a-amino p-cetoadipic

Succinyl CoA

Glycin

1.1.1.2 Tao porphobilinogen

ALA dtfdc tao thanh se di chuyen den bao ttfdng Tai day, hai phan ttf ALA ngtfng tu vdi

nhau (loai 2 phan ttf H20) va dong vdng pyrol tao thanh porphobilinogen vdi stf xiic tac ciia enzym ALA dehydratase (porphobilinogen synthase), enzym nay bi tfc che bdi chi kim loai (Pb).

Bon phan ttf porphobilinogen ket hdp vdi nhau, loai 3NH3 tao thanh mot tetrapyrol mach

thing va chat nay lai tidp tuc loai NH3 va dong vong, cac nhan pyrol ndi vdi nhau blng ciu ndi

-CH2 cd the tao thanh uroporphyrinogen I (enzym xiic tac ia uroporphyrinogen synthetase) va

uroporphyrinogen HI (enzym xuc tac la uroporphyrinogen cosynthetase).

Hai chat nay chi khac nhau ve vi tri ciia 2 nhdm the d nhan pyrol TV.

Binh thtfdng, dong phan dtfdc tao thanh hau nhtf deu la uroporphyrinogen III Khi cd rdi loanchuyen hda porphyrin mdi tao thanh uroporphyrinogen I

1.1.1.4 Tao coproporphyrinogen III , ,

~-Uroporphyrinogen III chuvdn thanh coproporphyrinogen III nhd stf khtf carboxyl cua tot

ca cac gdc acetat (A) d mach nhanh dd chuydn thanh cac gdc metyl (M) vdi stf xiic tac cuaenzym uroporphyrinogen decarboxylase

IV >NH HN<^ II

N III

,M

Coproporphyrinogen III

Coproporphyrinogen III rdi bao ttfdng vao ty thd d day, nd bi khtf carboxyl va oxy hoa

di chuydn hai nhdm thd propionat (- CH2 - CH2 - COOH) d2nhan pyrol I va II thanh 2nhdm

vinyl (- CH = CH2) tao thanh protoporphyrinogen III vdi stf xiic tac cua enzym

coproporphyrinogen oxydase (chi tac dong tren cd cha't la coproporphyrinogen III).

Protoporphyrinogen III tidp tuc bi oxy hda dd chuydn cau noi - CH2 - gitfa cac nhan pyrol thanh clu ndi methenyl (-CH=), tao protoporphyrin HI Enzym xiic tac laprotoporphyrinogen oxydase

,M

V

Protoporphyrin 111 (IX)

5 ty thd, protoporphyrin III kdt hdp vdi Fe2+ tao hem, nhd stf xuc tac cua enzym hem

synthase (ferrochelatase) Transferin cua huydt ttfdng (f3 globulin chtfa Fe +) lam nhiem vu van

chuyen sat den cac cd quan tao mau.

Qua trinh tdng hdp globin cung theo cd chd chung cua qua trinh sinh tong hdp protein

Nguyen lieu la cac acid amin cung stf tham gia cua nhidu ydu to khac nhtf acid nucleic (ADN va ARN), vitamin (acid folic, B12), cac cha't cung cap nang ltfdng (ATP, GTP).

1.3 Stf ke't hdp gitfa hem va globin dd tao thanh hemoglobin

" Sau khi dtfdc tong hdp xong, hem rdi ty thd ra bao ttfdng de kdt hdp vdi globin.

Stf kdt hdp gitfa hem va globin dtfdc thtfc hien qua lien kdt pho'i tri gitfa Fe cua hem vdi

nitd imidazol (histidin) ciia globin

Qua trinh tdng hdp hemoglobin xay ra chii ydu dcd quan tao mau nhtf tuy xtfdng va cac

hong cau non.

2 THOAI HOA HEMOGLOBIN

H6ng clu ngtfdi cd ddi song trung binh khodng 120 ngay, trong thdi gian nay Hb khong bi

bien doi Khi hong du chet, Hb se dtfdc giai phdng va bi thoai hda Trong didu kien sinh If d

ngtfdi trtfdng thanh binh thtfdng, cd ttf 1-2 x 108 hdng clu bi thoai hda trong 1gid.Trtf Fe va

globin, nhffng san pham thoai hda ciia porphyrin khong dtfdc cd the stf dung trd lai.

Stf thoai hda Hb xay ra chii yeu d nhffng te bao thuoc he tho'ng vdng noi mo nhtf gan,

lach, tuy xtfdng

Khi hemoglobin bi phan huy se giai phdng globin va hem:

- Globin chuyen hda theo con dtfdng thoai hda ciia protein noi bao de tao acid amin,

- Hem se thoai hda Ian ltfdt tao thanh sac td mat:

2.1 Tao biliverdin

Dtfdi tac dong ciia enzym hem oxygenase, vdng porphyrin cua hem bi md gitfa nhan pyrol

I va II bang each oxy hda va loai Cdcau ndi methenyl a dtfdi dang carbon monoxid (CO), giai

phdng sat dtfdi dang Fe3+ tao thanh biliverdin (sac td mat mau xanh).

Fe tach ra ket hdp vdi mot protid van chuyen la transferin, dtfdc mau dtfa den tuy xtfdng

Biliverdin nhanh chdng bi khtf d cau no'i - CH= tai vi tri y( cong Hd Cy, Nkdt hdp vdi

Hva cac no'i doi se di chuyen) tao thanh bilirubin (sac td mat cd mau vang xanh) vdi stf xiic tac

ciia enzym biliverdin reductase, co coenzym la NADPH cung cap hydro Bilirubin nay khd tan trong^ntfdc, cho phan tfng mau diazo cham va gian tidp, goi la bilirubin ttf do hay gian tiep Sau

khi tao thanh d mo ngoai vi, nd dtfdc chuyen vao mau ket hdp vdi albumin, globulin ciia huyet

thanh va theo mau den gan.Vi no la chat tan trong lipid nen co the tham qua mang te bao gan

dd dang va tach khoi albumin, globulin

Bilirubin

Hinh 4.2 Cau triic ciia sac td mat bilirubin.

2.2 Su* lien hr/p bilirubin d gan

Tai gan, bilirubin ttf do lien hdp vdi 1hay 2 phan ttf acid glucuronic tao thanh dang lien hdp bilirubinmonoglucuronat (20%) va bilirubindiglucuronat (80%).

Phan tfng xay ra gitfa 2 nhdm carboxyl (-COOH) ciia gd'c propionat (P) d mach nhanh ciia

bilirubin vdi nhdm OH ban acetal ciia acid glucuronic Acid glucuronic d dtfdi dang hoat hda

uridin diphosphat glucuronat va phan tfng lien hdp dtfdc xiic tac bdi enzym glucuronyl

transferase.

Bilirubin lien hdp tan dtfdc trong ntfdc, cho phan tfng mau diazo nhanh va trtfc tiep, goi la bilirubin trtfc tiep Bilirubin lien hdp dtfdc bai tie't vao mat theo mot cd che van chuyen chu dong

rdi theo 6'ng dan mat dd vao ruot

Binh thtfdng, trong mat ngtfdi biliverdin cd mot ltfdng rat nho con bilirubin chiem khoang

2.3 Su* biS'n ddi bilirubin d ruot

druot, dtfdi tac dong ciia enzym p-glucuronidase, bilirubin lien hdp bi thiiy phan giai

phdng bilirubin ttf do Ddn dai trang, dtfdi tac dung ciia cac enzym ciia vi khua'n ydm khi

bilirubin ttf do bi khtf oxy, bao hoa cac lien kdt doi di tao thanh urobilinogen va stercobilinogen'

^ Tren 50% cac san pha'm khtf nay ciia bilirubin dtfdc tai hap thu qua tinh mach ciia- mot phan theo mau ve gan , dtfdc oxy hda trd lai tai tao bilirubin rdi lai theo mat dd vao ruot tao thanh mot chu trinh gan ruot, mot phln nhd theo mau vd than va dao thai ra ngoai theo ntfdc tieu Phan con lai ciia urobilinogen va stercobilinogen d ruot khong dtfdc tai hap thu, se dtfdc

dao thai ra ngoai theo phan.

Trong phan va ntfdc tieu, urobilinogen va stercobilinogen bi oxy hda bdi oxy ciia khong

khi tao thanh urobilin va stercobilin cd mau vang cam, tao mau cho phan va ntfdc tieu.

Binh thtfdng ntfdc tieu chtfa rat it urobilinogen va urobilin (l-4mg/24gid), con

stercobilinogen trong phan cd khoang 40-280mg/24gid.

Khi bi tac mat, phan se mat mau do bilirubin lien hdp khong xuong ruot dtfdc, nen khong

tao urobilinogen va stercobilinogen

-JTrtfdng hdp thidu men vi khulh ruot (udng nhidu khang sinh, tre sd sinh thidu enzym cua

vi khuan ruot ) Bilirubin khong bi khtf druot, dtfdc <Jao thai nguyen ven ra phan va bi oxy hda

nhanh ngoai khong khi tao thanh biliverdin, lam cho phan cd mau xanh.

8H

Hinh 4.4 Cac san pham thoai hda ciia bilirubin.

Stercobilin

Tb noi mac vong mo

Hinh 4.5 Sd dd ciia stf thoai hda hemoglobin.

3 ROI LOAN CHUYEN HOA HEMOGLOBIN

3.1 Rdi loan sinh tdng hdp hemoglobin

S" hie'u hut cac enzym chinh trong qua trinh sinh tdng ho* porphyrin gay Udong cac ne

chat cua porphyrin trong hong cau cac dich c* thi va gan ;do a nhffng benh thuoc nhom b?nh

do do khong tdng h„pV hem de' tao hdng cau lam cho benh nhan bi thieu mau tram trong.

-Benh tf dong porphobilinogen trong gan gay roi loan than kinh.

3.1.2 Ro'i loan sinh td'ng hcfp globin ,*.,.• u „„„i^;n

Tren Mc US co khoang 300 loai gen tdng hdp nen cac chuc, globin cua hemoglobin.^

G5c loai nay chi khac nhau d1vi tri tren chudi polypeptid cua globin Su hay do, nho nay khong mty ddi dang ke' cau true va Cure n.ng cua phan * hemoglobin trff trU.ng ,p

al amin valin thay cho glutamat avi tri thff 6cua chudi (3 cua globin gay benh thieu mau hon

2>Zmi Hem hay lysin thay cho giu.amat ovi tri thff 6cua chuoi pcua globin gay b?nh

thieu mau hdng cau hinh bia

3.2 Roi loan thoai hda hemoglobin

Binh thtfdng, ndng do bilirubin toan phan trong mau vao khoang 0,2 -0,8 mg/lOOml, chii

yeu ddang ttf do (85%) con dang lien hdp chi cd ddang vdt (15%) Khi bilirubin trong mau'vtfdt

qua lmg/lOOmL se khuydch tan vao cac td chtfc dac biet la da va niem mac,vang da xua't hien

khi nong dp bilirubin toan ph£n >2-2,5mg/100 ml huydt thanh Stf tang ndng do bilirubin trong mau cd the do stf tao thanh bilirubin nhieu hdn stf dao thai d gan binh thtfdng; hay trtfdng hdp

gan bi suy nen stfdao thai bilirubin giam

Sau day la mot sdbenh ly vang da do ro'i loan thoai hda hemoglobin:

3.2.1 Vang da trtfdc gan

Xay ra do nhtfng nguyen nhan lam tan huyet hay tang stf pha huy hdng cau:

- Benh do Hb bat thtfdng (HbS, thalassemia )

- Benh di truyen do thie'u enzym G6PD

- Benh miln dich (truyen nham nhdm mau, bat dong nhdm mau - Rhesus )

- Benh mac phai (sd't ret, sot xuat huye't, nhilm trung, nmem doc dung moi htfu cd)

Nhtfng trtfdng hdp nay se tao ra mot ltfdng ldn bilirubin ttf do, khong dtfdc dua phan tfng

lien hdp d gan hetnen ndng do tang cao trong mdu (# 6-7mg%).

(3 tre sd sinh, do he tho'ng lien hdp, cac thu the d mang te'bao gan chtfa hoan chinh nen

cung lam tang bilirubin ttf do trong mau gay chtfng vang da sinh ly kha phd bien, thtfdng xay ra

vao ngay thtf 2 hay thtf 3 sau khi sinh, dac biet d tre sinh non.

Trong trtfdng hdp nay se khong cd bilirubin ttf do trong ntfdc tieu vi khong tan trong ntfdc

nen khong qua dtfdc than.

Ngoai ra, do ltfdng bilirubin tang nen urobilinogen va stercobilinogen se dtfdc dao thai

nhieu ra phan va ntfdc tieu Phan se cd mau vang slm

3.2.2 Vang da tai gan

Trong trtfdng hdp viem gan, td bao gan bi ton thtfdng lam giam kha nang lien hdpbilirubin, bilirubin ttf do trong mau tang va giam stercobilin trong phan

Ngoai ra, khi viem gan cac nhu mo gan bi phil nd chen ep cac vi qudn mat gay tac mat

lam cho bilirubin lien hdp khong xuo'ng ruot dtfdc, tang cao trong mau va xuat hien trong ntfdc

tieu (sac to'mat).

Urobilinogen ctfng cd the tang trong ntfdc tieu vi ton thtfdng gan lam giam kha nang tai tao bilirubin ttf urobilinogen, chat nay bi tf dong d gan, tran vao mau va dao thai ra ngoai theo

ntfdc tieu.

3.2.3 Vang da sau gan

Trong trtfdng hdp dtfdng dan mat bi tac (do bi soi mat, u dau tuy tang ), bilirubin lienhdp khong xuo'ng ruot dtfdc, bi tf lai d gan, tran vao mau va tang len rat cao, chiem ty le >80%

bilirubin toan phan Bilirubin lien hdp tan dtfdc trong ntfdc nen qua dtfdc cau than va thai nhieu

ra ntfdc tieu (cd sac to'mat trong ntfdc tieu)

Urobilinogen cd the tang do tf trong gan, tran vao mau va xuat hien nhieu / ntfdc tieu.Bilirubin lien hdp khong xuo'ng ruot dtfdc nen se khong cd urobilinogen va stercobilinogen dao thai ra ntfdc tidu va phan -> phan cd mau trang xam nhtf dat set.

TAI LIEU DOC THEM

1 Bo mon Hda sinh-Trtfdng Dai hoc Y ha Noi Hda sinh, NXB Y hoc Ha Noi, 2001.

2 Bo mon Hda sinh - Dai hoc Y dtfdc TPHCM, Hda sinh y hoc NXB Y hoc TP HCM 2003.

3 Bo Y Te, Vu Khoa hoc va Dao tao, Hda sinh hoc, NXB Y hoc Ha Noi, 2005.

4 Victor L Davison, Donald b Sittman, Biochemistry, 3th edition, Harwal Publishing, 1994.

5 Waiter X.Balcavage, Michael William King, Biochemistry (Examination &broad review)

6 Peter NCampbell Biochemistry Illustrated, 4th edition, Churchill hvmgston, 2000.

1 Robert K Murray, Daryl K Granner, Victor W Rodwell, Harper's Illustrated Biochemistry

27th edition-Lange Medical Books/Mcgraw-Hill, 2006.

CAUHOITtfLl/ONGGIA

Chon tap hdp cau tra 161 dung

1 Nhtfng nguyen nhan lam tan huydt hay tang stf pha huy hdng clu gay vang da la:

a Benh do Hb bat thtfdng (HbS, Thalassemia )

b Benh di truyen do thie'u enzym GePD

c Benh mien dich

d Benh mac phai (sot ret, sot xuat huydt, nhiem trung )

2 Phan tfng lien hdp bilirubin d gan:

a tao thanh dang lien hdp bilirubinmonoglucuronat (80%) va bihrubindiglucuronat (20 *) b.'xay ra gitfa 2nhdm carboxyl (-COOH) cua gdc propionat (P) dmach nhanh cua bilirubin

vdi nhdm OH ban acetal cua acid glucuronic

c Acid glucuronic ddang hoat hda uridin diphosphat glucuronat.

d dtfdc xiic tac bdi enzym glucuronyl tranferase

3 Bilirubin ttf do (gian tiep)

a khd tan trong ntfdc

b cho phan tfng diazo nhanh

c van chuydn trong mau ddang ket hdp vdi albumin, gobulin

d tham qua mang te bao gan de dang

4 Hay chon cac ydu td cd lien quan ddn cac benh ly sau day do roi loan chuyen hoa

hemoglobin:

1 Vang da trtfdc gan

2 Vang da tai gan

3 Vang da sau gan

a Bilirubin ttf do trong mau tang

b Bilirubin lien hdp trong mau tang

c Cd sac td mat trong ntfdc tieu

d Cd nhieu urobilinogen va stercobilinogen dao thai ra

CAU HOI NGHIEN CtfU BAI HOC

1 Trinh bay va giai thich qua trinh thoai hda bilirubin d ruot

2 Nguyen nhan va trieu chtfng ciia benh ly vang da trtfdc gan do rdi loan thoai hda hemoglobin

3 Neu cac hau qua do roi loan thoai hda hemoglobin trong trtfdng hdp bi tac mat.

CHUCfNG 5

CHUYEN HOA ACID NUCLEIC

1 'Vidt dtfdc sd dd stf thoai hoa base acid nucleic, base punn, base pynmidin.

2 Trinh bay dtfdc sd do tdng hdp nhan purin va pyrimidin.

3 Mo ta dtfdc qua trinh tdng hdp DNA, RNA.

4 Phan tich dtfdc cac rdi loan chuyen hda

Ta't ca cac te' bao cua cd thd sdng ddu co kha nang tdng hdp acid nucleic can thidt cho ta' bao

do do knina yeu cau phai c6 acid nucleic trong thtfc an Acid nucleic trong thtfc an khong co ynghia

2 lm.2 vdi cd thd Acid ribonucleic cua td bao luon ddi mdi nhanh chdng, no tang trong te bao

cung vdi sa tdng hdp protein Stf ddi mdi AND trong cac mo thi cham hdn nhieu, stf dot md, xay ra

trong cac te bao dang phat trien, te bao tai sinh.

1 THOAI HOA

Acid nucleic "% Nuc|e0,jd ^ ^ f Nucleosid ^ ^ Base nitd +Pentose

Nuclease la phosphodiesterase co trong dich tuy Nucleotidase la mot phospha.ase va

nnrleosidae la mot phosphorylase, ca hai enzym co trong dich mot.

^W^oi stf dung trd lai cho qua trinh phosphoryl hda hay dtfdc thai ra trong ntfdc tieu

^ VjTe ttfItfc fn tham gia dang kd vao qua trinh tdng hdp acid nucleic cho cd thd.

BTePurin va pyrimUUn dtfdc phdng thich trong qua trinh tieu hda caacid nucleic phan ldn

dtfdc thoai hda va dao thai, mot phdn dtfdc stf dung lai de tong hdp acid nucleic.

1.1 Thoai hoa cac base purin

Thnni hoa chinh cua base purin theo sd do sau: , , , >

J i " vat cd vu thoai hda base vdi hai loai phan tfng chtf yeu la KM amin thay phan va oxTho" (htah 5.1) 0ngtfdi, linh trtfdng, chim va mot sd bo sat san pham thoai hoa cuo,

L ctfabase purin 14 acU, uric va dtfdc dao thai ra ntfdc tidu Ndng dp acid unc trong mau ngtfd,

^Z^llTLg/lOOml Ltfdng acid uric trong ntfdc tidu 0,3-0,8g/24h Ltfdng acid unc trong

2 Shay ddfthfo chddo an,' dL biet tang vdi chddo n £u purin.gan than, th,t, cua) Trong benh gout, benh tang bach cau acid uric trong mau cd the tang den 7-8g/100ml.

O rnpt^so dong vat cd xtfdng sdng khac, acid uric bi thoai hda tidp tuc thanh allantoin nhd

u at oxydase O cac loai ca co xtfdng san pham cuo'i cung la allantoat d loai ca cd sun va dong vat

ltfdng ctf san pham cuo'i cung la ure Nhirng dong vat bien khong cd xtfdng so'ng san pham cuoi cung

la NH4 (hinh 5.1).

1.2 Thoai hoa cac base pyrimidin

Stf thoai hda base pyrimidin xay ra chu yeu d gan theo sd do sau:

NH;

N

NH Cytosin

ex NH Uracyl

HN \cAnH'

Dihydrothymin

:0-NH-CH?CH2COOH

NH2—CO b_Ureidoisobutyric

CH3NH2CH2CH2COOH

b_Aminoisobutyric

Hinh 5.2 Thoai hoa base nhan pyrimidin.

San pham thoai hda cudi cung cua pyrimidin la ure va p-alanin (ttf uracil) va aminoisobutyrat (ttf thymin) (hinh 5.2)

P-2 TONG HCfP

7 ,.» u^ tu~^ nhu rnn nhat trien cua te bao va mo, dac biet khi

Trong cd the nucleotid dtfdc tong hdp theo nhu cau pnai in

^ , • ^.>, ** „ hr^ nnrleotid la: (1) con dtfdng tong hop moi, (2) con

td bao phan chia Cd hai con dtfdng tong hdp nucieotia id.y &

dtfdng ^dn dung laV b^ang qua trinh phosphoribosyl hoa base hay nucleosid.

2.1.1 PRPP (5'-phosphoribosyI-l-Pyrophosphat) la cha't trung gian cd vai tro quan tron* tron*

PRPP dtfdc tao thanh ttf ribose-5-phosphat va adenosin triphosphat (ATP).

Ribose-5-phosphat + ATP -> PRPP + AMP

NguSn ribose-5-phosphat dtfdc cung cap ttf qua trinh chuyin hoa glucose hay ttf qua trinh

thoai hoa nucleosid.

PRPP dtfdc suf dung cho ca qua trinh tong hdp mdi va qua trinh tan dung lai Ndng do PRPP

trong te bao luon dtfdc dieu hoa va thtfdng d mire thap, qua trinh tong hdp PRPP dtfdc xiic tac bdi

PRPP synthetase va can Pi Binh thudng ndng do Pi trong te bao d mtfc thap nen hoat dong PRPP

synthetase thap, nhtfng khi Pi tang thi hoat dong enzym tang dang ke Ngtfdc lai ADP tfc chd hoat

dong PRPP synthetase.

2.1.2 Tong ho*p mdi nucleotid nhan purin

NguSn cacbon va nita di tSng hap nhan purin Nguon nay la glutamin, glycin, aspartat,

cacbon dioxid, va cacbon ciia folat Nhan purin dtfdc tdng hdp tren mot phan td PRPP (hinh 5.3)

C02 (ttf he ho hap)

A/j/V-MethenyLW10_Formyl/^ ^V^NH tet'rahydrofolattetrahydrofolat

Amin cua glutamin

Hinh 5.3 Nguon cacbon va nitd dung tdng hdp nhan purin.

Tong hap inosin 5'-monophosphat (IMP) IMP dtfdc tdng hdp qua 11 btfdc va stf dung 6 lien

kdt phosphat giau nang ltfdng (hinh 5.4) Day la qua trinh ton nhieu nang ltfdng.

TSng hap AMP va GMP tic IMP Ttf IMP qua qua trinh gan them nhdm amin cua aspartat cho

AMP Cung tir IMP qua qua trinh oxy hda va gan them nhdm amin cua glutamin cho GMP Ve mat

nang ltfdng thi GTP dtfdc suf dung cho qua trinh DVIP-»AMP va ATP dtfdc stf dung cho qua trinh

IMP->GMP Cd che nay giiip can bang ltfdng nucleotid adenin va guanin (hinh 5.5).

O ,/C

Hinh 5.5 Tdng hdp AMP va GMP ttf IMP.

Dieu hda qua trinh tong hap mdi nucleotid bang ca che tic chenguoc (feedback).

Hai enzym xiic tac ciia hai phan tfng dau tien trong qua trinh tdng hdp IMP la PRPP

synthetase va PRPP^ amidotransferase bi tfc che ngtfdc bdi IMP, GMP va AMP (Mnh 5.6).

Giai doan tong hdp adenylosuccinat ttf IMP bi tfc che bdi AMP va giai doan tong hdp XMP

bi tfc chd bdi GMP (hinh 5.6)

Ribose_ 5-phosphat

Q-<

AMP-0-< 0-< IMP

GMP-RIBOSE PHOSPHAT PYROPHOSPHOKINASE

(PRPP SYNTHASE)

PRPP

0 0-

0-PRPP GLUTAMYL

AMIDOTRANSFERASE

-GMP-

Hinh 5.6 Bieu hoa tong hdp AMP va GMP

2.1.3 Con dtfcmg "tan dung lai" nguon nucleosid hay base nittf <ti to'ng hdp nucleotid nhan

PUrln TU nguSn base purin cua qua trinh thoai hoa nucleotid co hai enzym chuyen biet xac tac

qua trinh vfn chuye'n ribose phosphat tfr PRPP sang base purin ttf do Hypotoniasg«an»,

Xil^««i^ xuc tac qua trinh tao nucleotid tt base guanin hay »W«^ va e^»

bi tic che' m IMP hay GMP Adenin phosphoribosyl transferase xuc tac gun doan tao AMP nf

adeninSnL5^ Nucleosid du*c phosphoryl hda bft nucleosid kinase thanh nucleoid 5'

monophXhat Tuy nhien con dUo^ng nay khong quan trong 3dong vat co vu Nucleoid bnase „

dong vat co vii chi co adenosin kinase.

Adenin

PHOSPHORIBOSYL TRANSFERASE

Hinh 5.7 Con dtfdng tan dung lai base nitd de tdng hdp nucleotid.

Gan la ndi tong hdp va cung cap chinh base nhan purin va nucleosid nhan purin cho qua trinh phosphoribosyl hda dcac to chtfc khong cd kha nang tong hdp mdi nucleotid Vi du nhtf nao, hong cau va bach ciu da nhan sii- dung ngudn base purin de tao nucleotid purin chtf khong tong hdp nhan

purin.

2.1.4 Tong hop mdi nhan pyrimidin

Nguon cacbon va nita su: dung cho tong hap nhan pyrimidin Nguon nay gdm glutamin,

aspartat va cacbon dioxid Khac vdi purin, nhan pyrirnidin khong dtfdc tdng hdp ttf PRPP ma sau khi

tong hdp hoan chinh nhan pyrimindin mdi ke't hdp vdi PRPP tao nucleotid (hinh 5.8).

Carbamyl phosphat

Tong hap uridin 5'-monophosphat (UMP) Giai doan dau tien la tdng hdp carbamoyl

phosphat Carbamoyl phosphat dtfdc tdng hdp trong te bao chat ttf glutamin va cacbon dioxid, ngoai

ra carbamoyl phosphat con dtfdc tdng hdp dty the te bao gan (chat trung gian cua qua trinh tdng hdp

ure) (hinh 5.9).

Tit UMP tong hap CTP va dTMP

Ttf UMP den CTP qua hai giai doan: (1) chuyen UMP thanh UTP nhd phosphat kinase, (2)

nhdm amino ciia glutamin ket hdp UTP cho CTP (hinh 5.9)

De tdng hdp dTMP nhd enzym ribonucleotid reductase khu" UDP thanh dUDP, tiep tiieo enzym thimidylat synthase xiic tac chuyen nhdm methyl cua N5,N10 methyltetrahydrofolat de tao

TMP (hinh 5.9).

C02 + Glutamin + ATP

© Carbamoylphosphat

Orotat

Dihydroorotat dehydrogenase

o

COO"

COO| Phosphoribosyl fj TN

transferase I H R-5-©

(OA)

NADPH H+ NADP+

Ribonucleotid reductase

Hinh 5.9 Tong hdp nhan pyrimidin.

Dieu hda sinh tong hap nucleotid pyrimidin

Nucleotid pyrimidin tfc che ngtfdc enzym aspartat transcarbamoylase va dihydro orotase.

2.1.5 Con dtfdng "tan dung lai" nguon base nitd de tdng hgfp nucleotid nhan pyrimidin

Cac base nitd nhan pyrimidin ttf qua trinh thoai hoa nucleotid la uracil va thymin.

• Uracil co the dtfdc chuyen thanh UMP qua 2 phan tfng:

Phan tfng dau tien dtfdi tac dung cua uridin phosphorylase

Uracil + Ribose 1-phosphat -> Uridin + PiPhan tfng thtf hai dtfdc xuc tac bdi uridin kinase

Uridin + ATP -^ UMP + ADP

• Cytidin cung dtfdc phosphoryl hoa bdi uridin kinase.

• Thymin dtfdc chuyen thanh dTMP qua hai giai doan:

Thymin phosphorylase chuyen thymin thanh thymidin

Thymin + deoxyribose 1-phosphat -* thymidin + PiThymidin kinase chuyen thymidin thanh dTMP

Thymidin + ATP -> dTMP + ADP

2.1.6 Tong hdp deoxyrubonucleotid

Deoxyribonucleotid dtfdc tao thanh bdi qua trinh knur ribonucleotid Cac deoxyribonucleotid

dtfdc tao thanh do qua trinh khir bdi ribonucleotid reductase la dADP, dCDP, dGDP, dUDP Rieng

dTMP dtfdc tao ttf dUMP vdi xuc tac cuathymidylat synthase.

2.2.Tdng htfp acid nucleic

2.2.1 Tong hcfp ADN

Tdng hdp ADN la mot qua trinh tai ban xay ra d hau het te bao va dac biet phtfc tap d te bao

co nhan Qua trinh nay dtfdc nghien ctfu dau tien d mtfc enzym bdi Kornberg Qua nghien ctfu ciia

Kornberg va nhieu tac gia khac ngtfdi ta gia thiet stf tai ban ADN qua nhieu giai doan theo trinh ttf

sau (hinh 5.10):

Giai doan mot dau

Nhan dien diem khdi dau (ori) cua qua trinh tai ban: tai diem khdi dau xay ra stf ket hdp cua

protein nhan dien diem khdi dau vdi mot doan ADN (ori) Vi du d E.Coli diem md dau la doan ori

Cse ket hdp vdi protein dnaA tao phtfc hdp khdi dau Stf ket hdp gitfa ori va protein giiip xac dinh

diem khdi dau cua qua trinh tai ban ADN.

Dtfdi tac dung ciia helicase sdi doi ADN dtfdc thao xoan Tren cac doan ADN ddn sau khi

dtfdc thao xoan cd nhieu phan nr SSB protein gan vao nham gitf cau triic sdi ddn khong bi xoan kep

trd lai.

ADN primase xiic tac tdng hdp nhtfng sdi ARN mdi ngan khoang 10-200 nucleotid tren chuoi

cham Cac mau ARN mdi nay can cho stf tdng hdp cac doan okazaki

Giai doan keo ddi

Sdi nhanh (leading strand) dtfdc tdng hdp lien, tuc dtfdi tac dung cua ADN polymerase.

Tren sdi cham (lagging strand) ADN polymerase IH xiic tac tdng hdp nhirng doan okazaki (1000-2000 nucleotid) noi tiep vdi ARN mdi Sau do ARN mdi dtfdc tach ra va cac doan okazaki

nay no'i lai vdi nhau nhd enzym ADN ligase.

Giai doan ket thiic

Ngtfdi ta con biet rat it ve giai doan nay

Chuoi nhanh

(Leading strand)

Polymerase

Helicase Primase

Ligase

Hinh 5.10 Tong hdp AND.

Protein ket hdp diem khdi dau

(Ori_.bin.ding protein)

•• SSB (DNA binding protein)

Chuoi cham

(Lagging strand)

Cac thtfdng tdn co the xay ra tren ADN

Stf sai lam khi kep doi trong qua trinh tdi ban co the tich luy tao dot bien, 6 E Coli ty le sai

lam la 10"9- 10"10 Nhtfng may man la phan ldn cac sai lam xay ra tren ADN khong ma hda protein

va them vao do cac sai lam nay cd the dtfdc stfa chtfa.

Sai lam tao ra do cac tdc nhan moi trtfdng, do cac yeu to vat ly va hoa hoc Cac thtfdng tdn

nay dtfdc chia lam 4 loai.

Bien doi tren mot base

- Khtf purin

- Khu* amin cua cytosin va uracil

- Knur amin ciia adenin va hypoxanthin

- Alkyl hoa base

- Them vao hay mat di mot nucleotid

- Sirdung thanh phan cd cau tao ttfdng ttf base nitd de tdng hdp nucleotid

Bien doi tren hai base

- Tia UV tao dimer gitfa 2 thymin

Mat doan

- Do btfc xa ion hda

- Do chat phdng xa

- Do cac goc oxy hoa ttf do

Xuat hien cac lien ket

- Gitfa cac base trong cung day hay gitfa hai day

Cac he thonp; sufa chfla thtfdng tdn

Dd stfa chtfa cac sai sot va thtfdng tdn xay ra tren cac ADN , te bao co hang loat cac enzym,

protein tham gia trong qua trinh nay Ngtfdi ta chia thanh bo'n he thdng suTa chtfa nhtf sau:

Su-achXasti kep doi khong dung trong qua trinh tdi ban

6 E Coli cd 3protein (Mut S, Mut Cva Mut H) tham gia xac dinh sai lam tren chuoi ADN.

Tie'p theo cac enzym ligase, polymerase, SSB loai bo sai lam va tao lai chuoi.

Hinh 5.11 SuTa chtfa stf kep doi khong dung

He thong stia chUa theo each cat nucleotid

' He thdng nay stfa chtfa cac thtfdng tdn ca'u triic mot doan tren ADN Cac enzym tham gia nhtf

exonuclease, ADN polymerase va ADN ligase

XXXX

Nhan biet sai lam va thao xoan

I Cat doan oligonucleotid

-XXXX tong hdp bo sung

va gan lai

Hinh 5.12 Sufa chtfa theo eachcat nucleotid

Stia chila theo each cat base

Stfa chtfa cac thtfdng tdn nhtf khtf purin, cac base khong binh thtfdng, cac base bi alkyl hda sir

l-° dime cic enzym tham §ia M thong stfa chtfa nay la ADN glycosylase, nuclease ADN

polymerase va ADN ligase

Hinh 5.13 Sufa chtfa theo each cat base.

He thdng siia chita theo each cat chuoi doi.

Hai protein can cho he thdng stfa chtfa nay la Ku va ADN-PK (ADN protein kinase) se gan

vao hai dau ciia doan ADN giiip tach rdi hai dau, tiep theo hai dau nay dtfdc thao xoan Cac

nucleotid sai se dtfdc cat bo bdi exonuclease, sau do ADN ligase se gan hai doan lai

Hinh 5.14 Stfa chtfa theo each cat chuoi doi.

2.2.2 Tong hdp ARN (transcription)

ARN polymerase phu thuoc ARN la enzym phu trach tdng hdp ARN, khong can mdi de batdau tdng hdp, nd gan vao mot vi tri khdi dau dac biet tren chuoi ADN khuon goi la promoter va stf

tdng hdp dtfdc khdi dau Ddn vi sao chep dtfdc dinh nghia la mot vung tren doan ADN khuon co

chtfa cac vi tri dau hieu cho stf khdi dau, keo dai va dau hieu ket thuc ARN dtfdc tdng hdp co chieu

ttf 5'-3'.

2.2.2.1 Cac giai doan ciia mot qua trinh tdng hcfp ARN

Giai dan khdi dau

ARN lien ket vdi promoter ADN tai vi tri -35 tao thanh phtfc hdp dong Sau do ARN

polymerase di chuyen de'n vi tri -10 tao thanh phtfc hdp md Mot vung ciia chudi xoan kep dtfdc

thao xoan ARN polymerase tien hanh tdng hdp ARN

Giai doan keo ddi

ARN di chuyen dan doc chieu dai ciia doan ADN theo chieu 3'-5", ARN dtfdc tdng hdp co

chieu 5'-3\ Giai doan keo dai chudi dtfdc tiep tuc den khi polymerase gap doan ket thuc

Giai doan ket thuc

Dau hieu ket thuc la mot doan cac nucleotid A va doan cd chtfa cac nucleotid cd tinh chat bdsung tao thanh kep doi xoan kep tren ADN khuon Sau khi ARN tdng hdp mot loat cac U, doan ARN trtfdc do cd the ttf bd sung thanh doan kep doi gap khiic thi ARN ngtfng tdng hdp va dtfdc giai

phdng khoi ADN.

Tao lien ket

•AAAAAAAA

Dau hieu Ket thuc

2.2.2.2 Su* hoan thien cac ARN sau qua trinh sao chep

Cac ARN ttf qua trinh sao chep la cac tien ARN Cac phan tir nay phai trai qua qua trinh

hoan thien de tao cac ARN trtfdng thanh

Stf hoan thien ARN thong tin (ARNm)

Qua trinh bien ddi ARNm gdm cac giai doan sau: :

- Cat cac doan itron (doan khong ma hda)

.•'•- - Taomu 7-methylguanosind dau 5'.

- Gan them duoi poly A

5 Mu

OTOT^S

Hinh 5.17 Stf hoan thien ARNm.

Stf hoan thien ARN van chuyen (ARNt)

Qua trinh hoan thien gdm cac btfdc sau:

- Cat bo cac doan itron ndi lien exon

- Cat cac nucleotid d dau 5'va 3'.

- Gan them CCA d dau 3'.

- Thay ddi mot sdbase

Stf hoan thien ARN ribosom (ARNr)

28S.

TienRNAr 45 S

5-8 S 18S

*-"28'S

Hinh 5.18 Stf hoan thien ARNr.

3 BENH LIEN QUAN DEN ROI LOAN CHUYEN HOA NUCLEOTID

3.1 Rdi loan thoai hoa nucleotid purin

3'L1* ^Tolig benh gout, acid uric trong mau co thd tang 7-8g/100ml din ddn stf ke't tinh va ling

dong urat trong cac td chtfc sun, bao gan, tui nhay cua cac khdp, th^n, doi khi ca trong da va cd.

Xung quanh chd tf dong urat ke't tinh la td ehiic viem, hinh thanh to chtfc hat bao quanh cac mo

chtfc va bang each nay tao cac hat gout to nho khac nhau thtfdng gap dcac khdp ngon chan ngon

tay gay viem khdp man tinh va bien dang khdp Thtfdng cac benh nhan co khuynh htfdng xd ctfng dong mach va tang huyet ap Neu uric ket tinh nhieu trong than co the gay suy chtfc nang than.

Nguyen nhan:

Acid uric tang do cac nguyen nhan sau:

• 0 vai benh nhan, PRPP synthase khong dap tfng vdi cd che tfc che' ngtfdc (feedback) cua

purin nucleosid diphosphat.

• Do thieu hut mot phan HGPRT (hypoxanthin-guanin phosphoribosyl transferase) nen din

tdi tang ltfdng PRPP trong te bao va din theo stf gia tang tdng hdp mdi nhan purin Stf thieu hut mot

phan khong gay trieu chtfng than kinh nhtf hoi chtfng Lesch-Nyhan.

Bieu tri:

Allopurinol la dtfdc pham quan trong dieu tri gout: nd tfc che'qua trinh san xuat acid uric.

(1) Allopurinol bi oxy hda bdi xanthin oxidase cho oxy purinol

(2) Oxy purinol ke't hdp chat vdi xanthin oxydase nen tfc che' kha nang oxy hda ciia enzymnay.

(3) Allopurinol phan tfng vdi PRPP vdi xiic tac ciia HGPRT giiip lam giam PRPP va do ddlam giam qua trinh tdng hdp mdi purin

Colchichin la dtfdc pham cd tinh khang viem dung cho gout, nd giiip ngan stf tap trung bach

cau d cac td chtfc viem »

3.1.2 Hoi chiing Lesch-Nyhan

Hoi chtfng di truyen do gen tren nhiem sac the X Do suy giam hoan toan hoat dong ciia

HGPRT nen gay ra tang qua trinh tdng hdp purin Vi HGPRT d benh nhan hau nhtf khong hoat

dong nen con dtfdng "tan dung lai" hypoxanthin va guanin khong hoat dong keo theo viec tangPRPP dong thdi IMP va GMP giam Dieu nay din de'n tang tdng hdp mdi purin

Trieu chtfng bao gdm: tang uric mau, tao sdi uric va dac biet la trieu chtfng than kinh nhtf

cham phat trien tri nao Trieu chtfng than kinh cd the vi nao la td chtfc stf dung con dtfdng tdng hdp

nucleotid chinh la con dtfdng "tan dung lai".

Dieu tri: allopurinol lam giam stf tao acid uric nhtfng khong cd tac dung gidm trieu chtfng thankinh Va khong co hoat tinh ciia HGPRT nen PRPP khong the phan tfng vdi allopurinol do dd khonglam giam qua trinh tdng hdp mdi purin

3.1.3 Benh Von Gierke

Do thieu nang hoat tinh ciia glucose 6-phosphatase dan de'n stf tang ribose phosphat Tangribose phosphat dan de'n tang PRPP, PRPP gay tang qua trinh tdng hdp mdi purin

J 1.4 B^nh giam uric mau

Giam" uric mau dong thdi vdi tang dao thai hypoxanthin va xanthin do suy giam xanthinoxydase nguyen nhan ttf tdn thtfdng gan hay khie'm khuye't tren gen Trieu chtfng la tang xanthin

trong ntfdc tieu va soi xanthin.

3.1.5 Roi loan gay suy giam midn d|ch

* Do suy giam adenosin deaminase (ADA)

Khi suy giam ADA ltfdng deoxyadenosin va adenosin se cao do khong dtfdc tie'p tuc thoai hda

chuyen thanh deoxyinosin va inosin Ndng do cao dATP (do giam thoai hda) se tfc che'ribonucleotidreductase va do do tfc che tdng hdp DNA Cac te' bao bach cau dac biet la te bao B va te' bao T se

giam do khong tang sinh binh thtfdng gay suy giam mien dich.

Trieu chtfng suy giam mien dich xua't hien khi benh nhan dtfdc 6thang tudi la nhiem khua'n

man tinh va cham phat tridn Va benh nhan thtfdng cheft sau 18 tuoi.

Dieu tri: ghep tuy xtfdng.

0 Do suy sidm purin nucleosid phosphorylase

vTec suy giam enzym nay gay tich luy dGTP Giong nhu- dATP, dGTP tfc che ribonucleotid

Trong truing hdp nay chi co te' bao Tbi giam, con te' bao Bkhong b» anh hUdng (chua ro

" ChUa co phirong phap dieu tri Benh nhan dUdc nuoi trong moi trtrong it nhiem khuan.

3.2 Roi loan thoai hoa nucleotid pyrimidin

Khong giong nhu san pha^m thoai hoa cua purin, san pham thoai hoa cua pynmidin de tan trong nude hot nen it gay cac trieu chUng hdn trong truing hdp roi loan thoai hoa San pham thoai

h6a cOa primidin tang mi tie'u trong trUdng hdp ung th.bach cau, khi chup tia Xdo co sU pha huy

ADN.

3 2 1 Benh tang acid orotic trong ntfdc tieu

' ' Do'khiem khuye't orotat phosphoribosyltransferaseva orotidin 5'-phosphat decarboxylase nen

oroudin S'-phosphat khong dude chuye'n thanh UMP va vi the' tich luy Khi UMP giam se giam tong

hdp ADN va ARN gay trieu chtfng la thieu mau va ch$m phat tnen.

TAI LIEU DOC THEM

1 Bo mon Hoa sinh-Trtfdng Dai hoc Yha Noi Hda sinh, NXB Yhpc Ha Npi^OOL

2 Bo mon Hoa sinh -Dai hoc Ydtfdc TPHCM, Hda sinh yhoc NXB Yhoc TP HCM 2003.

3 Bo YTd, Vu Khoa hoc va Dao tao, Hda sinh hoc, NXB Yhoc Ha Noi, 2005

4* Victor LDavison, Donald b Sittman, Biochemistry, 3*edition, Harwal Publishing, 1994.

5* PNCampbell Biochemistry Illustrated, 4th edition, Churchill Hvingston, 2000

6 Robert KMurray, Daryl K Granner, Victor W Rodwell, Harper's Illustrated Biochemistry 27

edition-Lange Medical Books/Mcgraw-Hill, 2006.

CAU HOI TU LU0NG GIA

Chon mot hay nhieu cau diing

1 Nguyen nhan tang acid uric trong benh Gout la do

' a PRPP synthase khong dap tfng vdi tac dung tfc chd cua purin nucleosid diphosphat

b Do thidu hut mot phin hypoxanthin-guanin phosphoribosyl transferase

c Do tang ltfdng PRPP trong te bao

d Do tang tdng hdp mdi nhan purin

2 Cac roi loan chuyen hoa trong hoi chtfng Lesch-Nyhan

a Qua"trinh phosphoribosyl hda hypoxanthin va guanin khong hoat dong

b Giam IMP va GMP

c Giam PRPP

7 Trong qua trinh tdng hdp nhan purin, phan tfng tie'p theo cua Formyl glicinamid

ribosyl-5-phosphat la phan tfng vdi

10 Phan tfng chinh trong qua trinh thoai hda nucleotid nhan pyrimidin

a Thiiy phan phan dtfdng

b Khtf amin

c Oxy hda

d Thiiy phan lien ke't amid

Dien vao ch6 trong

11 Rdi loan do suy giam Adenosin deaminase cd bieu hien la (A) do

14.PRPP dtfdc stf dung cho qua trinh (A) va qua trinh (B)

15 Phan tfng chinh ciia qua trinh tong hdp nucleotid purin dnao, hdng cau va bach cau da nhan la

A

B

3 Giai thich dtfdc cac cd che' dieu hoa chuyen hoa d mtfc te bao.

Mac du co nhffng con dtfdng chuyen hoa rieng biet nhtfng cac chuydn hoa ciiaglucid, lipid, protein va acid nucleic deu co nhffng diem chung va co mdi lien quanmat thie't vdi nhau hinh thanh nen qua trinh chuyen hda chung ciia cd the

Sir tdng hdp va thoai hoa*cac chat trong cd the luon dtfdc kiem soat chat chebdi te'bao va dtfdc dieu hoa phu hdp vdi nhu cau ciia cd the

1 LIEN QUAN GI0A CAC QUA TRINH CHUYEN HOA

1.1 So* dd lien quan chuyen hoa cac chat

Stf lien quan giffa cac qua trinh chuyen hoa trong cd the dtfdc bieu thi qua sd dd sau

(hinh 6.1)

a-Ceto Glu

ffinh 6.1 Sd do lien quan chuyen hoa cac chat.

1.2- Sii thong nhat chuyen hda

The hien d cac mat sau :

^'^^^^^^^^^rk «in *.« -. :•-•• - Cac con dtfdng chuye'n hoa cua glucid, lipid, protem o

-acetyl CoA bi dot chay trong chu trmh acid citric tao CU2va 2

Qua qua trinh ho ha'p te bao, ^ ^ ^ ^ (khtf carboxyl bdi

rd chd va he thdng enzym chung cua qua trinh nay, tao ^ 2

decarboxylase), tach dan ttf 2H va aua 101 w2

hoa sinh hoc) tao thanh H20.

+Tich trff va suf dung nang Wcfng

Nang ltfdng giai phdng tff stf oxy hoa glucid, lipid, protein 6* cac mtfc do khac nhau nhirng deu dtTdc stf dung bang 2dang nhu* nhau la toa nhiet va dtf trff dtfdi dang

ATP Chung ta khong the phan biet diTdc nguon gdc ATP ttf chuyen hoa nao ciia cac

chat.

1.3- Su* bien doi qua lai giffa glucid, lipid va protein

Su* bien ddi qua lai giffa glucid, lipid va protein thong qua nhffng chat «nga ba

dtfdng » Nhffng chat nay vtfa la san pham thoai hoa chung, vtfa la tien chat cho stf tdng hdp cac cha't Vi du: pyruvat, oxaloacetat, acetylCoA.

Mot vi du chtfng minh la khi stf dung acetat 14C dtfa vao cd the sinh vat thi tha'y

xuat hi^n 14C trong cac phan ttf glucid, lipid, protein Dieu nay chtfng to rang acetat latien chat chung ciia glucid, lipid, protein

Pyruvat la san pham khtf amin ciia acid amin alanin Pyruvat co the dtfdc tdng hdp thanh glucid qua qua trinh tan tao glucose; dong thdi pyruvat co the chuyen hda

thanh acetyl CoA tham gia vao qua trinh tdng hdp acid beo.

Phosphoglyceraldehyd (PGA) la san pham ttf su* khu* hydro ciia glycerol co

nguon goc lipid (thanh PDA (phosphodioxyaceton) rdi thanh PGA) PGA co the tdng

hdp glucid qua qua trinh tan tao glucose hoac chuyen thanh pyruvat Pyruvat co the

dtfdc amin hda thanh acid amin la alanin.

Nhu* vay ta thay co stf bie'n ddi qua lai giffa glucid, lipid va protein Tuy nhien,

chung khong the thay the' nhau hoan toan dtTdc vi:

- Glucid la nguon nang ltfdng chii yeu ciia cd the (1 glucose di den chu trinh acid citric

cung cap 38 ATP).

- Do'i vdi lipid: co cac acid beo can thiet ma cd the khong the tdng hdp dtfdc (acid

linoleic, acid Hnolenic).

- Do'i vdi protein: co cac acid amin can thie't ma cd the khong the tdng hdp dtfdc.

Do do de cd the phat trien tot, can che do dinh dtfdng hdp ly, day du cac chat

vdi ty le nhat dinh.

1.4 Suf lien hcTp giffa cac phan tfng va cac qua trinh

Stf lien quan chuyen hoa con la stf lien hdp giffa cac phan tfng va qua trinh

- Phan tfng lien hcTp: ket hdp 2 phan tfng giai phdng (thoai hoa) va thu (tdng hdp)

nang ltfdng.

Vidu:

Glucose -^- «=^- • Glucose -6-phosphat

Phan tfng tdng hdp glucose-6-phosphat la phan tfng thu nang ltfdng va phan

tfng thiiy phan ATP la phan tfng giai phong nang ltfdng

- Cac qua trinh chuyen hda: lien quan vdi nhau qua nhffng san pham chuyen hoa

' '•" • -f Thoai hoa glucid (theo con dtfdng hexose monophosphat) cung cap

NADPHH+ cho stf tdng hdp acid beo va ribose-5-phosphat cho stf tdng hdp nucleosid,

nucleotid va acid nucleic.

+ Thoai hoa glucid (theo con dtfdng hexose diphosphat) cung cap oxaloacetic

giup ngtfng tu acetyl CoA (san pham ciia stf oxy hoa acid beo) vao chu trinh acid citric.

+ Chu trinh acid citric lien quan vdi chu trinh ure qua aspartat (aspartat dong vai tro trung gian chuyen van nhdm NH3 cho chu trinh ure).

+ Chu trinh acid citric cung cap succinyl-CoA cho qua trinh tao Hem

1.5 Quan he chuyen hoa giffa cac bao quan trong te bao

Ty the:

- la ndi xay ra qua trinh chuyen hoa nang ltfdng manh me

- la ndi cung cap nang ltfdng (ATP) cho cac bo phan khac ciia te bao, dam bao cho

cac hoat dong ciia te bao.

Nhan te bao:

- tdng hdp ARN cho stf tdng hdp protein d ribbosom.

- tdng hdp NAD cho cac qua trinh khtf hydro cua ty the va cac ndi khac.

1.6 Quan he chuyen hoa giffa cac mo

Ngoai cac qua trinh chuyen hoa chung, mdi mo deu co dac diem va chtfc nang

chuyen hoa rieng, nhtfng co lien quan Ian nhau

1.6.1 Gan (trung tarn trong moi lien quan chuyen hda giffa cac mo)

+ Co chtfc nang glycogen (tdng hdp glycogen dtf trff va phan ly thanh glucosevao mau khi can de cung cap cho cac mo)

+ Qua trinh p-oxy hoa acid beo bao hoa xay ra chii yeu cf gan

Hinh 6.2 Quan he chuyen hoa giffa cac mo.

Chii thich: OA: oxaloacetat; CT: chu trinh.

1.6.2 Nao

Nao can dtfdc cung cap thtfdng xuyen glucose va oxy Nguon nang hrdng chii

ye'u cung cap cho nao la ttf glucose mau thoai hoa theo con dtfdng hexose diphosphat

hieu khi Khi doi, cac the ceton (acetoacetat va (3- hydroxybutyrat) thay the' glucose

cung cap nang ltfdng cho nao.

1.6.3 Co*

Nguon nang ltfdng chtf ye'u cung cap cho cd la stf oxy hoa glucose, acid beo va

the ceton LtTdng glycogen d cd chiem khoang 1/3 tdng glycogen cd the Ltfdng

glycogen nay dtfdc chuyen thanh glucose-6-phosphat nhanh chong rdi thoai hoa tie'ptuc theo ca 2 con dtfdng hieu khi va yem khi

Cd khong giai phdng glucose ttf do vao mau do khong co

Hinh 6.3 Quan he chuyen hda giffa gan va cd.

Chu thich: G6P: glucose-6-phosphat.

Khi cd nghi, acid beo va the ceton dufdc stf dung lam chat dot Cd tim stf dung

acetoacetat nhieu hdn so vdi glucose

1.6.3 Mo md

La ndi dtf trff triglycerid Tai day xay ra qua trinh tdng hdp va phan giai

triglycerid (hinh 6.4).

Hinh 6.4 Qua trinh tdng hdp va phan giai triglycerid d mo md.

Chu thich: AB: acid beo; VLDL (very low density lipoprotein): lipoprotein ty trong

rat thap; TG: triglycerid

2 DIEU HOA CHUYEN HOA

Mot dac didm ciia cd thd sdng la kha nang ttf didu hda Stf didu hda dtfdc thd

hien d hai mtfc do khac nhau: mtfc te' bao (didu hda chuydn hda) va toan cd the (kiem

soat chuydn hda nhd hormon, than kinh) Cd che' cua stf didu hda bao gid cung la cd

che' phan ttf Trong mot te' bao, cd che' didu hda chu ydu la anh hiring den hoat tinh

cua enzym hoac anh hiring den sinh tdng hdp enzym.

2.1 Dieu hoa nhd* ctf che lam thay ddi hoat tinh cua enzym

(Xem phdn 4chtfong 6: Enzym va xuc tdc sinh hoc, Hoa sinh hoc tap 1, NXB Yhoc

2.2 Didu hoa nho- ctf che' anh htftfng den suf sinh tdng htfp enzym: quan niem vdoperon

Ngirdi ta da biet cac vi khua'n tdng hdp nhffng enzym thich hdp cho minh tuy

thuoc vao mdi trtfdng dinh dtfdng.

Co 2 loai enzym:

- Enzym cau tao: la nhffng thanh phan cd ban ciia hoat dong td bao, vi du

enzym ciia stf dtfdng phan

Nhffng enzym nay dtTdc san xua't vdi mot ltfdng khong thay ddi mac du cac dieu kien chuyen hda thay ddi.

-Enzym cam tfng: cac enzym nay trai lai chi dtfdc tdng hdp vdi mot ltfdng can

thie't khi te bao can de'n.

Jacob va Monod (1961) dtfa ra mo hinh operon de giai thich cd che didu hda tdng hdp ciia enzym nhtf sau: mot operon la mot tap hdp ciia cac gen tao thanh motddn vi chtfc nang Mot operon gdm (hinh 6.5):

+Cac gen cau true (cistron): chtfa ma tdng hdp protein dac trung.

+Mot gen khdi dong P(promotor): la ndi gan ARN polymerase Gen khdi dong

cd 2 trung tarn: mot trung tarn gan ARN polymerase va mot trung tarn gan phtfc hdp

CRP-AMP vdng (CRP = C-reactive protein: la protein thu nhan AMP vdng).

+ Gen dieu khien O (operator): gen nay sat vdi gen P cd chtfc nang chi huy stf

hoat dong ciia cac gen cau true hoac lam ngtfng hoat dong ciia cac gen nay Operator

khi dtfdc ket hdp vdi chat kim ham R (represseur) san xuat ra bdi gen dieu hda se

ngan chan qua trinh phien ma Trong trtfdng hdp nay operon se khong hoat dong:

operon dong (hinh 6.5)

+ Gen dieu hda R (regulator): gen nay tdng hdp ra chat kim ham R (ban chat la

1protein) Cha't kim ham co 2 ai ltfc: hoac ke't hdp vdi gen O, hoac ke't hdp vdi cha't

cam tfng Ai ltfc cua chat kim ham do'i vdi gen O diXdc thay ddi bdi tac dung ciia cha't

cam tfng hoac chat dong kim ham (corepressor) Khi cha't kim ham ket hdp vdi chat

cam tfng thi gen O dtfdc giai kim ham va qua trinh phien ma cac gen cau true dtfdc

tien hanh Trong trtfdng hdp nay goi la operon mo* (hinh 6.6).

Gen dieu hoa

Gen dieu hoa Gen P Gen O

ARNm

Chat cam tfng Protein kim ham R

Protein cau true

Hinh 6.6 Stf dieu khien tong hdp protein :he thong operon md.

- Operon lactose

Ly thuye't vd operon ciia Jacob va Monod da dtfdc chtfng minh bang thtfc

nghiem khi nudi cay E coli Trong mdi trtfdng khong cd lactose hoac khong cd mot

chat cam tfng khac thi khong tha'y cd stf tdng hdp cac enzym chuydn hda lactose Khi

co mat lactose hay mot cha't cam tfng khac (nhtf isopropylthiogalactosid), cha't kim

ham ket hdp vdi lactose (hoac cha't cam tfng khac) tao phtfc hdp "cam tfng-kim ham"

khong gan dtfdc vao gen O Ltfc nay cd stf phien ma cac gen ca'u true tao ra cac

ARNm de cd stf tdng hdp ba enzym chuydn hda lactose la: (3-galactosidase, permease

va acetylase (hinh 6.7)