CHUYEN HOA ACID NUCLEIC
Hinh 5.7. Con dtfdng tan dung lai base nitd de tdng hdp nucleotid
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 enzym
nay.
(3) Allopurinol phan tfng vdi PRPP vdi xiic tac ciia HGPRT giiip lam giam PRPP va do dd lam 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. ằ 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 tang PRPP 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 than kinh. Va khong co hoat tinh ciia HGPRT nen PRPP khong the phan tfng vdi allopurinol do dd khong lam 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. Tang ribose 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 xanthin oxydase 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'ribonucleotid reductase 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
reductase nhtfng d mtfc do khac nhau. , . , , , * , u ,
Trong truing hdp nay chi co te' bao Tbi giam, con te' bao Bkhong bằ anh hUdng (chua ro
nguyen nhln). Trieu chtfng la nhiem khuan man tinh. _ 3
" 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
d. Tang PRPP