Bài giảng Hóa sinh 2: Phần 1 - Trường ĐH Võ Trường Toản

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Phần 1 của tập bài giảng Hóa sinh 2 gồm 3 chương đầu tiên, cung cấp cho sinh viên những nội dung tổng quan về: chuyển hóa glucid; chuyển hóa của các monosaccarid khác; điều hòa chuyển hóa glucose và glycogen-hoạt động của hormon và những nhân tố khác trong quá trình chuyển hóa; chuyển hóa lipid; chuyển hóa protein và acid amin - sinh tổng hợp protein;... Mời các bạn cùng tham khảo chi tiết nội dung bài giảng!

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Nội dung Text: Bài giảng Hóa sinh 2: Phần 1 - Trường ĐH Võ Trường Toản

TRƯỜNG ĐẠI HỌC VÕ TRƯỜNG TOẢN KHOA DƯỢC  BÀI GIẢNG MÔN HỌC HÓA SINH 2 Đơn vị biên soạn: XÁC NHẬN CỦA BCN KHOA DƯỢC Hậu Giang – Năm 2013
MUC LUC Trang 1 Lofi ndi dau 2 Muc luc Chu'o'ng 1. Chuyen hoa glucid Pham Thanh Trang 4 4 1. Dai ciTdng 6 2. Thoai hoa glucose 16 3. Tdnghdp 4. Chuyen hoa cua cac monosaccarid khac 20 5. Su* chuyen hoa cua glucose d mot so trang thai 22 6. Lien quan chuyen hoa cua gluose 24 24 7. Van chuyen glucose qua mang te bao 8. Dieu hoa chuyen hoa glucose va glycogen-hoat dong ciia hormon 25 va nhffng nhan to khac trong qua trinh chuyen hoa 26 9. Roi loan chuyen hoa glucid Chtftfng 2. Chuyen hoa lipid Tran Thi Tudng Linh 31 31 1. Sir tieu hoa va hap thu lipid trong thtfc an 32 2. Suf thoai hoa lipid 42 3. Suf sinh tdng hop lipid 50 4. Suf chuyen hoa cholesterol Chu'o'ng 3. Chuyen hoa protein va acidamin- Sinh tong hcfp protein Tran Thanh Nhan 59 59 1. Bien hoa protein 62 2. Thoai hoa acid amin 84 3. Tong hdp acid amin 80 4. Sinh tdng hdp protein Chu'o'ng 4. Chuyen hoa hemoglobin Tran Thi Tudng Linh 102 102 1. Sinh tdng hop hemoglobin 105 2. Thoai hoa hemoglobin 108 3. Roi loan chuyen hoa hemoglobin Chu'o'ng 5. Chuyen hoa acid nucleic Pham Thanh Trang 112 112 1. Thoai hoa 114 2. Tdnghdp
3. Benh lien quan den roi loan chuyen hoa nucleotid 128 Chu'o'ng 6. Lien quan va dieu hoa chuyen hoa Tran Thanh Nhan 133 1. Lien quan gitfa cac qua trinh chuyen hoa 133 2. Dieu hoa chuyen hoa 138 Chufcfng 7. Su* trao doi ntftfc va cac chat dien giai Tran Thi Tudng Linh 146 1. Nude trong cd the 146 2. Cac chat vo cd trong cd the 150 3. SU trao doi nUdc va cac chat dien giai 153 Chuftfng 8. Thang bang acid - base Tran Thi Tudng Linh 159 1. Cd so hoa ly cua thang bang acid - base 159 2. Cachedemcuacdthe 161 3. SU dieu hoa thang bang acid - base ciia cd the 163 4. R6'i loan thang bang acid - base 164 Chu'o'ng 9. Hoa sinh than va nutfc tieu Ngo Kien Due 167 1. Than 167 2. Nufdc tieu 172 3. Thuf nghiem tham do chuc nang than 178 Chu'o'ng 10. Hoa sinh gan Ngo Kien Due 183 1. Thanh phan hoa hoc cua gan 183 2. Cac chuc phan hoa sinh cua gan 184 3. NhUng xet nghiem hoa sinh he thong gan mat 191 Chu'o'ng 11. Hoa sinh mau Tran Thanh Nhan 196 1. DaicUdng 196 2. Tinh chat ly hoa ciia mau 196 3. Thanh phan hoa hoc ciia mau 199 210 Dap an 212 Tai lieu tham khao
CHLfCfNG 1 CHUYEN HOA GLUCID MUC TIEU 1. Viet dUdc sd do va xac dinh vai tro ciia nhirng con dtfcmg chuyen hoa chinh ciia glucid. 2. Neu dtfdc y nghia va moi lien quan giffa con dtfdng dutmg phan va chu trinh pentose. 3. Neu dtfdc dac diem chuyen hoa glucid d cac mo. 4. Trinh bay dtfdc cac qua trinh tdng hdp glucid trong cd the. 5. Trinh bay dtfdc chuyen hoa ciia frutose, galactose, mannose. 6. Trinh bay dtfdc chuyen hoa ciia glucid trong cac trtfdng hdp sau khi an, khi doi. 7. Trinh bay dtfdc su* dieu hoa va nhtfng roi loan ciiachuyen hoa glucid. l.DAICl/CfNG Chuyen hoa glucid la mot trong nhirng qua trinh chuyen hoa quan trong trong cd the song, chii yeu nham cung cap nang Itfdng cho te bao hoat dong. Ngoai ra stf chuyen hoa nay con cung cap nhieu san pham chuyen hoa trung gian quan trong. Qua trinh chuyen hoa glucid co lien quan chat che vdi su" chuyen hoa cac chat khac trong cd the, nhat la do'i vdi chuyen hoa lipid, acid amin va acid nucleic. Nhu cau glucid ciia ngtfdi trtfdng thanh la 300 - 500g trong 24h. Khi tang Itfdng lipid va protid trong khau phan an thi nhu cau glucid co the giam thap. Trong cd the ngtfdi va dong vatcao cap, glucid ton tai dUdi 3 dang: - Dang du" trtf la glycogen, tap trung chu yeu d gan va cd - Dang van chuyen la glucose ttf do trong mau va cacdich ciia cd the - Dang tham gia cau tao trong cac to chtfc cd the 1.1. Nguon glucose ciia cof the • Nguon glucose ngoai sinh: la ngudn glucid ttf thtfc an, bao gdm: Tinh bot: la thtfc an glucid chii yeu ciia ngtfdi, co trong cac hat ngu coc, cii. Glycogen: co trong cac to chtfc va cd dong vat. Cellulose: co trong rau va mot so'qua Cac disaccarid: thtfdng gap la saccarose (dtfcmg mia), lactose (dtfdng sira), maltose (mach nha) ... Cac monosaccarid co trong thtfc an vdi lUdng it, thUdng gap la glucose (nho), fructose (trai cay), mannose, ribose ... Su tieu hoa va hap thu glucid Qua trinh tieu hoa glucid t\X thUc an thUc chat la qua trinh thuy phan cac polysaccarid va disaccarid dirdi tac dung cua cac enzym cf dtfdng tieu hoa thanh cac monosccarid. Enzym thuy phan tinh bot va glycogen la amylase ciia nUdc bot va dich tuy. Cd hai loai amylase la a- amylase va (3-amylase. p-amylase cd trong mot so thUc vat, a-amylase co trong nufdc bot va dich tuy, ca hai deu thuy phan lien ket a-l->4 . P-amylase tac dung dphln dau mach nen diTdc goi la exoamylase. a-amylase thi thuy phan cac lien ket 6giifa nen co ten la endoamylase, 6he thong tieu hoa a-amylase la enzym thuy phan amylose va amylopectin (thanh phln ciia tinh bot va glycogen) cho maltose, a-amylase la enzym cln Ca2+. Vi a-amylase khong cit drfdc lien ke't a-l->6 nen san pham trong qua trinh thuy phan amylopectin la cac oligosaccarid (dextrin). Ruot chi cd the' hap thu monosaccaraid nen oligosaccarid tiep tuc dUdc thuy phan tiep bdi cac 4
oligosaccaridase ciia mot non. Cac disaccarid trong thtfc an nhtf lactose va saccarose cung vdi cac san pham thuy phan ciia tinh bot va glycogen se bi thuy phan dtfdi tac dung ciia maltase, saccarase, lactase de cho san pham cuo'i cung la cac monosaccarid chii ye'u laglucose va mot so itfructose va galactose. Stf thieu hut lactase d ruot dan den tich tu lactose gay tieu chay khi dung lactose vi lactose khong dtfdc hap thu se len men bdi vi khuan va ap ltfc tham thau tang gay hut nirdc vao long ruot. Tat ca cac monosccarid deu dtfdc hap thu hoan toan d ruot non, stf hap thu tot nhat d phan dau ciia ruot non. To'c do hap thu ciia cac monosaccarid: galactose(HO) > glucose (100) > fructose (43) > mannose (19) > pentose (15-19). Stf hap thu cd 2 cd che: (1) stf kkuech tan dctn gian, phu thuoc vao gradient ndng do cua monosaccarid giffa te bao mang ruot va mau; (2) stfvan chuyen tich ctfc, khong phu thuoc vao gradient ndng do ma phu thuoc vao nang Itfdng cung cap, cd che' nay xay ra doi vdi glucose va galactose. Stf hap thu monosaccarid d ruot non cung bi anh htfdng bdi mot so tac nhan: Thyroxin lam :ang qua trinh hap thu cac hexose hay stf thay doi ndng do ciia cac cation dac bietla K+ lam tang lap thu glucose. Stf hap thu cac hexose tdi tfu nhat khi cd mat cac vitamin nhom B nhtf thiamin, pyridoxin va pantothenic acid. • Nguon glucose noi sinh Nguon carbohydrat noi sinh chinh la glycogen cua gan. Ngoai glycogen trong cd the con iguon carbohydrat nho la galactose, mannose va pentose, nhtfng chat nay cd kha nang chuyen thanh glucose. Ngoai ra trong cd the c6n cd nhirng thanh phan khong phai carbohydrat cd kha nang tao glucose nhtf: (1) cac acid amin dtfdc xem la mot trong nhtfng nguon nguyen lieu de tdng hdp carbohydrat (2) lipid, cdc acid beo khong cd kha nang chuyen thanh glucose nhtfng phan glycerol itfdc xem la nguon tao glucose. 1.2. Stf dung glucose ciia cd the7 Thoai hoa De cung cap ndng lUOng cho cd the glucose bi thoai hoa hoan toan thanh C02 va H20 (dtfdng pyruvat), qua trinh nay xay ra d tat ca cac mo. Tong hop dang du trU Khi khong cd nhu cau nang Itfdng khan cap hay nhu cau tdng hdp cac san pham dac biet thi Itfdng thffa glucose se dtfdc dtf trtf dtfdi dang glycogen 6* gan va mo. Ltfdng glycogen dtf trff rong cd the co gidi nan, khi vtfdt gidi han nay ltfdng glucose thiia se dtfdc chuyen thanh acid beo a dtf trtf dtfdi dang triglycerid trong mo md. Sit dung tong hop cac thanhphan khac Mot phan glucose dtfdc stfdung de tdng hdp: - Ribose va deoxyribose can cho tdng hdp acid nucleic. - Mannose, glucosamin, galactosamin, neuramic acid(thanh phan ciia cac mucopolysaccharid va glycoprotein) - Glucuronic acid (tham gia trong cac phan tfng khtf doc -detoxication). - Galactose (trong thanh phan ciia glycolipid va lactose)
- Sir dung tdng hdp acid beo va acid amin. (1) Cd nhieu acid amin khong cd trong khau phan an nhtfng van xuat hien trong thanh phan protein ciia mo cd the, do la nhtfng acid amin do cd the ttf tdng hdp. Cacacid amin nay dtfdc tdng hdp ttf khung carbon la glucose hay chat chuyen hoa ciia glucose. (2) Qua trinh chuyen glucose thanh acid beo xay ra khi vtfdt qua gidi han dtf trtf d dang glycogen. 2. THOAI HOA GLUCOSE Trong te bao ciia cac to chtfc, glucose ttf do dtfdc tao ra mot phan do thoai hoa glycogen (it) hoac do tebao lay ttf mau ngoai bien vao. Glucose chi cd the di vao con dtfdng thoai hoa khi no 6" dang glucose-6-phosphat. Ttf glucose-6-phosphat cd the theo nhieu con dtfdng thoai hoa: (1) Con dtfdng dubngphan (glycolysis), (2) Con dtfdng Hexose monophosphat hay chu trinh pentose phosphat, (3) Con dtfdng Uronic acid. 2.1. Thoai hoa glucose theo con dtfdng duftng phan - glycolysis 2.1.1. Dtfdng phan-Glycolysis Qua trinh oxi hda glucose den pyruvat goi la qua trinh dtfdng phan (glycolysis). Phan ixng dau tien ciia con dtfdng dtfdng phan la phan tfng phosphoryl hda glucose 6* C-6 bdi hexokinase. Tie'p theo glucose-6-phosphat dtfdc isome hda thanh fructose-6-phosphat va fructose-6-phosphat dtfdc phosphoryl hda tie'p tuc dtfdi tac dung enzym phosphofructokinase cho fructose 1,6- diphospHat. Qua trinh phosphoryl hda vdi stf tham gia ciia 2 phan ttf ATP va stf hien dien ciia Mg""". Dtfdi tac dung ciia aldolase, fructose 1,6-diphosphat bi phan doi thanh hai manh3C la glyceraldehyd-3-phosphat (G3P) va dihydroxyaceton phosphat (DHAP). Chi cd G3P tie'p tuc thoai hda. Stf can bang thanh phan hai loai triose-phosphat nay dtfdc dieu khiIn bdi triose- phosphat isomerase do do ca 2 triose ttf hexose deu cd the dtfdc stf dung hoan toan. Mat khac dihydroxyaceton phosphat cd the chuyen hda theo dtfdng khac, do la khi cd stf hien dien DPNH enzym glycerophosphat dehydrogensase se khii dihydroxyaceton phosphat thanh glycerol cung cap cho tdng hdp lipid (hinh 1.1).
©Phosphoryl hoa Hexokinase ©Isomer hoa Glucose-e-phosphat Phosphoglucoisomerase OCH, /-» CH,OH OH ©Phosphoryl hoa Fructose- e-phosphat Phosphofructokinase ©Phan doi Fructose-1 >6-diphosphat Aldolase DHAP ©Isomer hoa Trios e phosphat isomerase H CH20 U c=o CHOH CHpOI CH20 Dihydroxyaceton Glyceraldehyd-3-phosphat phosphat Hinh 1.1. Dtfdng phan-Glycolysis G3P tie'p tuc bi oxi hoa va phosphoryl hda dtfdi tac dung glycerldehyd -3-phophat dehydrogenase cho 1,3-diphophoglycerat va giai doan nay tao ra mot NADH H+, trong dieu kien hie'u khi NADH H+ se di vao chuoi ho hap te bad tao ra 3 ATP. 1,3-diphophoglycerat cd xu litfdng chuyen nhdm acyl-phosphat cho ADP de tao ATP va phan tfng nay xiic tac bdi phosphoglyceratkinase. Den thdi diem nay tdng so' ATP tao ra bdi con dtfdng glycolysis la 0. Con dtfdng glycolysis that stf cho nang ltfdng d cac phan irng con lai. 3-phosphoglycerat qua giai doan isomer hda cho 2-phophoglycerat va tie'p tuc bi khtf ntfdc bdi enolase cho phophoenolpyruvat (PEP). Cuoi cung vdi xiic tac pyruvat kinase tie'p tuc qua trinh phosphoryl hda d mifc cd chat, PEP chuyen phosphat cho ADP va cho pyruvat (hinh 1.2).
n 1=0 CHOH 2 G3P CH20 © Oxi hoa va Glyceraldehyd-3- phosphat phosphoryl hoa Glyceraldehyd- 3-Phosphat o dehydrogenase II CHOH DPG CH20 © Phosphoryl hoa 1.3-diphosphoglycerat d mufc chat nen Phosphoglycerat kinase coo' CHOH 3PG CH20 3- phosphoglycerat © Isome hoa Phosphoglycerat mutase coo 2PG CH—0 CH,OH © Dehydrat hoa 2- phosphoglycerat Enolase coo PEP C—Ow CH2 Phosphoenolpyruvat 0 Phosphoryl hoa d mufc chat nen Pyruvat kinase coo I c=o I Pyruvat CH, Pyruvat Hinh 1.2. Dtfdng phan-glycolysis. 2.1.2. Chuyen hda tiep tuc cua acid pyruvic Trong dieu kien hieu khi Trong dieu kien te'bao cua to chtfc dtfdc cung cap du oxy, acid pyruvic se dtfdc chuen vao trong ty the, d do nd bi khuf carboxyl oxy hda thanh acetyl CoA. Sau do acetyl CoA tie'p tuc di vao chu trinh Krebs de tiep tuc thoai hda. Phan tfng khtf carboxyl oxy hda ciia acid pyruvic thtfc ra la mot chuoi phan tfng dtfdc xiic tac bdi mot phtfc hdp da enzym, phtfc hdp nay co stf tham gia ciia cac coenzym: thiamin pyrophosphat, NAD, FAD...
K Mg2+ CH3CO^s CH3COCOOH + |)Lipoic Xipoic J^ •» > |>ipoic l/Lipoic + CO 2 S lpp Hs acid pyruvic CH3COWS Hs J/Lipoic + CoA-SH ^- Xipoic + CH3COVW S-CoA HS HSX FAD NADH? \f FADH2 NAD S JyLipoic S Trong dieu kien yem khi Trong trtfdng hdp co cd yem khi khi cd van dong ctfdng do cao hay d nhtfng vi khuan lactic >6ng trong dieu kien khong cd oxy, acid pyruvic bi khtf thanh acid lactic Lactic cooh dehydrogenase COOH C=0 ^-^v > CH-OH CHj NADHH+ NAD+ CH3 Acid pyruvic Acid lactic Trong qua trinh len men rtfdu, acid pyruvic bi khir thanh etanol. pyruvat alcol ^OOH decarboxylase H dehydrogenase 0=0 "^ *" c=o /^-^ * fH2OH I A I .../..., x . ' CH3 CO2 CH3 NADHH+ NAD+ CH3 Acid pyruvic Acetaldehyd Etanol 2.1.3. Nang Itffing tao ra qua qua trinh thoai hda glucose theo con duffing duffing phan Qua trinh thoai hda glucose theo con dtfdng dtfdng phan chii ye'u nham cung cap nang Itfdng cho te' bao hoat dong. Nang Itfdng tao ra dtfdc tap trung vao cac lien ket phosphat giau nang ltfdng trong phan ttf ATP.
Glycogen Glucose ATP vADP Glucose-1 -© Glucose-6-© Fructose-6-© ATP i ADP Fructose-1,6-di® Dihydroxyaceton-© Glyceraldehyd- 3-© I —I Glycerol- © 1,3- di© glyceric acid + t __ADP Glycerol NADHH+(x2) *• ->+ATP(x2) 3- © glyceric acid \ 2- © glyceric acid 2-© enolglycene I ^-—AD? |
2.1.4. Dufing ph&n (glycolysis) 6* co* - Chu trinh Cori Cd xtfdng la'y nang Itfdng chii yeu ttf qua trinh thoai hoa glucose bang con dtfdng dtfdng phan (glycolysis). Khi cd hoat dong gang stfc hay vdi ctfdng do nhanh glycogen ciia cd dtfdc huy dong phan giai cho glucose-6-phosphat de thoai hoa tao nang ltfdng. Nhtfng he ho hap va tuan hoan khong cung cap du oxy cho cd de oxi hoa hoan toan ltfdng glucose nay. Do do mot phan pyruvat se khong bi oxy hoa tie'p tuc ma bi khu' bdi lactat dehydrogenase ciia cd cho lactat. Sau do lactat dtfdc phdng thich vao mau va dtfdc gan stf dung de tan tao glucose. Lactat sau khi vao gan dtfdc oxy hda thanh pyruvat, pyruvat tiep tuc tham gia vao qua trinh tan tao glucose (gluconeogenesis) cho glucose. Glucose sau do dtfdc dtfa vao mau va van chuyen den cd de to'ng hdp dang glycogen dtf trtf (hinh 1.4a val.4b). Gan Mau Cd Glycogen Glucose- Glucose 6_phosphat t I Lactat -
2.2. Thoai hoa glucose theo con dtfdng hexose monophosphat (pentose phosphat) Stf oxy hda glucose theo con dtfdng nay xay ra d cac to chtfc song song vdi con dtfdng dtfdng phan, song chiem ti le thap hdn nhieu (7-10%). Tuy nhien d mot so te bao va to chtfc nhtf hong cau, gan, tuyen stfa trong thcfi ky hoat dong, to chtfc md... stf thoai hda glucose theo con dtfdng nay lai chiem tfu the. Chu trinh pentose phosphat cung la mot con dtfdng thoai hda glucose nhtfng khong tao ATP ma cd hai chtfc nang la: (1) tao NADPH cung cap cho qua trinh tong hdp acid beo va steroid va (2) tong hdp ribose cung cap cho qua trinh tong hdp nucleotid va acid nucleic. Chu trinh pentose phosphat xay ra d te bao chat va chu ye'u d gan, mo md, vo thtfdng than, tuyen giap, hong cau, tinh hoan va tuyen stfa trong thdi ky hoat dong. Chu trinh nay chiem ti le thap dcd xtfdng va tuyen stfa trong thdi gian khong hoat dong. d nhtfng mo ma chu trinh pentose phosphat hoat dong cao se sir dung NADPH do chu trinh nay tao ra de tham gia khtf trong qua trinh tong hcfp acid beo, steroid, acid amin va gluthathion. Dac biet d hong cau chu trinh pentose cung cap NADPH de khtf glutathion d dang oxy hoa tao glutathion dang khtf. Phan tfng nay rat quan trong vi glutathion dang knur cd vai trd phan huy H202, vi H202 lam giam thdi gian "song va gay ton hai mang te bao hong cau dan den tieu huyet. Mot benh cd tinh chat di truyen do thieu mot enzym trong con dtfdng pentos phosphat la glucose-6-phosphat dehydrogenase (G-6-DP), dan den thieu NADPH va dac biet d te bao hong cau va gay ra tieu huyet (hemolytic anemia) khi benh nhan suf dung cac thuoc tao ra cac goc cd tinh oxy hda nhtf thuoc sot ret primaquin, aspirin, sulfonamid hay khi benh nhan an cac loai dau. 12
Hs ^0H ^ C — COOH l NADP NADPHH i i HCOH HCOH HCOH HOCH I 0 ±J. HOCH l 0 HOCH i HCOH HCOH HCOH I I HC- HC HCOH I CH20—0 CH20—H | _C=0 1 O HCOH | HOCH HC- HCOH CH20—0 CH20—0 Ribose-5-phosphat Xylulose-5-phosphat TPP Transketolase Mg2- Transketolase CH2OH _C_=0 s\ H C=0 CH2OH HCOH HOCH (HCOH)2 HC=0 CH20—0 CH20—0 GIyceraIdehyd-3-phos phat Goc glycoaldehyd " SedoheptuIose-7 CH2OH l HOC H C=0 OH HcOH J HCHOH ;oh HCOH | l l Trasnsaldolase HCOH HC ' CH20—0 CH20—0 Erythrose-4-phosphat Fructos e-6-phos phat JU- Hinh 1.6. Con dtfdng hexose monophosphat. Con dtfdng nay la mot chu trinh trong do ctf 3 phan ttf glucose-6-phosphat di vao se tao 3 phan ttf C02 va 3 phan tuf pentose phosphat, tie'p theo la mot chuoi phan tfng bien doi de 3 phan ttf pentose phospphat tren tao thanh 2 phan ttf glucose-6-phosphat va mot phan ttf 13
M» W^-"^^^ su thoai hoa tiep nhCmg san phosphat, fructose-6-phosphat, fructose-l,6-diphosphat (hinh 1.7). Glucose Glycogen NADH H+ acid nucleic Ribulose5P Xylulose 5P Ribose5P dihydroxyaceton-® glyceraldehyd-© Pyruvic ffinh 1.7. M6'i Hen quan giffa con Al8ng glycolysis va hexose monophosphat. v
CH20-® CH20H UDP.gh. CH2QH 0 H (gGlucosemutase H/j °vh pyrophosphorylase h *——0 ^o /OH i O- H OH H OH UTP (g),® H~0H Glucose-6-phosphat Qucose-1-phosphat UDP-glucose NADt UDP-glucose ) NADH2 ^ dehydrogenase CH,OH UDP H OH H OH H OH NAD+ a. gluconic a. glucuronic a. UDP glucuronic NADH2 CH2OH l H0C c=o HOC |11 o hoch" He—' HCOH HOCH l CH20—0 CH2OH Xylulose a. Ascorbic Hinh 1.8. Con dtfdng uronic. 2.4. Thuy phan glycogen (glycogenosis) Trong qua trinh thuy phan glycogen, ca lien ket ot-l->4 va cc-l-»6 deu dtfdc thuy giai. Cd 4 phan tfng vdi stf tham gia ciia enzym: (1) phosphorylase tuy phan lien ket a-1,4 (2) cac phan tfng cat nhanh va cat lien ket a-l-»6, (3) phosphoglucomutase chuyen glucose-1-phosphat thanh glucose-6-phosphat, (4) glucose-6-phosphatase chuyen glucose-6-phosphat thanh glucose (hinh 1.9, 1.10). Trong cd vi thieu enzym glucose 6-phosphatase nen glycogen ciia cd khong la nguon cung cap glucose trtfc tiep cho nguon glucose mau, tuy nhien nd lai la nguon cung cap nang Itfdng cho stf co cd do glucose 6-phosphat di vao thoai hda theo con dtfdng dtfdng phan. O 1>6-glucosidase >. Hinh 1.9. Cat nhanh trong thuy phan glycogen Glycogen Pi ^ Phophorylase Glucoset-Phosphat Glucose 6_phosphat Glucose Glucose 6jphosphatase Phosphoglucomutase Hinh 1.10. Thuy phan glycogen (glycogenosis). 15
3. TONG HOfP 3.1. Ta^i tao glucose (gluconeogenesis) Be tao nang ltfdng phan ldn cac to chtfc cd the chuyen hda cac nguon carbon khac ngoai glucose nhtf cac dtfdng khac glucose, triacylglycerol, acid amin, pyruvat... Tuy nhien nguon carbon can ban va duy nhat ma nao va he thong than kinh trung tfdng sir dung la glucose. Mot so mo khac cung suf dung glucose la nguon can ban nhtf cd, phan tiiy than, tinh hoan va hong cau. Vi vay cac te bao phai cd kha nang ttf tong htfp glucose ttf nhtfng nguyen lieu khac de duy tri nong do glucose mau nam trong gidi han va gidi han nay d ngtfdi ttfdng doi hep, ltfdng glucose mau nay nham duy tri hoat dong cd the dac biet la nao va he than kinh trung tfdng va cung cap cho qua trinh to'ng hdp glycogen dtf trtf. Nhu cau glucose ciia nao ngtfdi ttfdng do'i ldn khoang 120g/ngay so vdi to'ng ltfdng glucose suT dung ciia toan bo cd the la 160g/ngay. To'ng Itfdng glucose cd trong glycogen dtf trtf ciia toan bo cd the d bat ky thdi diem nao la 190g va ltfdng glucose trong toan bo dich cd the la 20g. Do do ltfdng glucose dtf trtf ciia cd the chi du cung cap cho nhu cau glucose trong mot ngay. Vi vay khi thdi gian nliin doi keo dai tren mot ngay hay khi cd the phai hoat dong d ctfdng do cao (vi du nhtf mot cuoc chay marathon) ltfdng glucose dtf trtf gan nhtf can kiet va glucose phai dtfdc to'ng hdp mdi (ttf cac nguyen lieu khac), qua trinh tdng hdp mdi glucose dtfdc goi la tan taoglucose (gluconeogenesis). Tan tao glucose (gluconeogenesis) dtfdc dinh nghia nhtf la qua trinh sinh to'ng hdp glucose ttf nguon nguyen lieu cd cau tao 3 va 4 carbon. Cac thanh phan chinh tham gia tan tao glucose la lactat, san pham ttf qua trinh dtfdng phan xay ra d cd xtfdng va hong cau; acid amin, ttf nguon thtfc an hay ttf qua trinh phan giai protein ciia cd trong thdi gian doi va xa bffa an, trong 20 acid amin dprotein trtf lysin va leusin cac acid amin con lai deu san sang tham gia qua trinh to'ng hdp cho glucose; alanin, ttf chu trinh gluose-alanin d cd; propionat, san pham ttf qua trinh thoai hda acid beo hay acid amin; glycerol, san pham trong qua trinh thoai hoa lipid. Va qua trinh nay xay ra trong phan te' bao chat ciia te bao (hinh 1.11). 16
Glucose t Glucose-6-phosphat t Fructose-6-phosphat t Fructose-1 -6-diphosphat Dihydroxyaceton Glyceraldehyd-3-phosphat phosphat t t t t Phosphoenolpyruvat Glycerol-3-phosphat Oxaloacetat Succinyl CdA Methylmalonyl CoA A A Glycerol Propionyl CoA Hinh 1.11. Qua trinh tan tao glucose (gluconeogenesis). Qua trinh tan tao glucose (gluconeogenesis) xay ra chinh d gan, ngoai ra con cd mot con dtfdng phu xay ra d phan vo than. Glucose dtfdc tao mdi chii ye'u cung cap cho nao, mo than kinh va cd xtfdng. Ngoai ra mot phan se cung cap cho qua trinh tdng hdp cac hexoamin,'cac polysaccarid phtfc tap va cac ilycoprotein hay glycolipid. J.2. T6ng hop glycogen Hai to chtfc tdng hdp glycogen manh nhat trong cd the la gan va cd. Trong cd the glycogen dtf trtf chii ye'u d gan va cd, ty le cao nhat d gan 2%-8%. Cd chtfa l%-3% glycogen nhtfng vi khoi ltfdng cd ldn nen tdng ltfdng glycogen ciia cd la nhieu nhat. Glycogen ciia gan la dang dtf trtf chung cho toan cd the ngtfdc lai glycogen trong cd chi dtf trtf rieng cho cd ma thoi. O cd xtfdng glycogen la nguon nang ltfdng chinh cung cap cho qua trinh co cd. Gan lay nguon nang ltfdng chinh ttf qua trinh thoai hoa acid beo, rieng nguon glycogen ciia gan chii yeu cung cap cho glucose mau va van chuyen den cac mo khac de thoai hoa tao nang ltfdng. Do do gan dtfdc xem la to chtfc dieu hoa glucose ciia cd the vdi vai tro dieu hoa Itfdng glucose mau thong qua dieu hoa qua trinh tdng hdp va phan giai glycogen bang enzym glycogen synthase va phosphorylase. De thich hdp vdi vai tro tren gan chtfa ltfdng ldn glycogen, 2% den 8% trong ltfdng gan. 6 gan mtfc toi da ciia qua trinh tdng hdp glycogen v^jcua^jjui-^ftifrTJhan giai tRddHQ TOfSN twcvd VIEN 17
glycogen ttfdng dtfdng nhau, nhtfng d cd thi ciia qua trinh phan giai glycogen cd the gap 300 Ian qua trinh tdng hdp glycogen. Cac enzym ciia qua trinh tdng hdp va phan giai glycogen d gan va cd nhtf nhau nhtfng noi tiet td dieu khien lai khac nhau. Nguyen lieu de tdng hdp glycogen ciia te bao la glucose. Cac td chtfc lay glucose ttf mau tuan hoan, con td chtfc gan ngoai Itfdng glucose do mau dtfa den (sau khi an) con mot ltfdng ldn glucose do te bao gan ttf tdng hdp ttf cac monosaccarid ngoai glucose, cac acid amin, glycerol, acid lactic... (khi an thtfc an chtfa nhieu cac monosaccarid khac, khi doi, khi van cd nhieu ...). Glucose ttf do d mau tuan hoan, sau khi qua mang tebao bi phosphoryl hda thanh glucose-6-phosphat, sau do dtfdc dong phan hda thanh glucose-1-phosphat de tham gia tdng hdp glycogen. Tong hop mach thang La qua trinh tap cac lien ket 1,4 glucosid gitfa cac phan tu: glucose de keo dai mach thang ciia phan tu* glycogen (hinh 1.12). Glucose ATP Hexokinase ~j |^ADP Glucose-6-phosphat \ / it Phosphoglucomutase Glucose-1-phosphat / \| UTP UDP- Glc pyrophosphorylase CPPj UDP-Glc O, UDP Bo$n glycogen Glcn c Glycogensynthase UDP Glycogen Glc::r l. Hinh 1.12. To'ng hdp mach thang ciia glycogen. Tong hop mach nhanh La qua trinh tao cac lien ket oc-l->6 glucosid trong phan ttf glycogen. Trong qua trinh chuoi thang, khi chudi thang da kha dai enzym amylose (1-^4, l->6) transglucosesidase se cat mot doan dau cua mach thang (it nhat la 6 phan tu* glucose) sau do chuyen den gan vao OH cua C6 cua phan tii glucose cua cung chuoi hoac chudi khac. Sau do mach nhanh mdi tao thanh lai dtfdc keo dai. 3.3. Tong hcfp lactose Disaccarid duy nhat dtfdc tdng hdp d cd the ngtfdi va dong vat cao cap la lactose. Lactose dtfdc tdng hdp d tuyen stfa ciia phu ntf d thdi ky cd thai va cho con bii. Nguyen lieu de tdng hdp lactose la glucose ttf mau hoac do phan huy glycogen (hinh 1.13). 18
Heroskinase Glucose -• G-6-P ATP ADP Phosphoglucomutase Phosphorylase Glycogen G-l-P. UTP ADP Pi UDP glucose \// se \ uridyl P-P UDP-G UDP ATP epimerase / * Lactose synthetase UDP-gal ^—• Lactose Glucose'' Hinh 1.13.Tong hdp lactose. 3.4. Tong ho"p glycoprotein Giai doan dau tien trong qua trinh tdng hdp glycoprotein la tdng hdp chuoi oligosaccarid gan vdi lipid. Phan lipid tham gia la dolichol phosphat, tiep theo la qua trinh tdng hdp chuoi oligosaccarid. Qua trinh tren xay ra d ltfdi noi chat, btfdc ke tiep chuoi oligosaccarid ciia oligosaccarid-DPP se dtfdc chuyen sang lien ket vdi mot polypeptid (hinh 1.14). 19
—Dolichol UDP-HfelcNAd |c CHgXg^-Dolichol UMP UDP—(GlcNAd UDP Q>--Dolichol 5 GD P—/Man\ —Dolichol 4 Doi—(Jy~\ Man, 4 GDP •4 Dol-^> 4GDP-/ManN 3>—Dolichol UDP-ZqiA gXf^-Dolichol Asn-X-Ser/Thr-polypeptid ) •