Bg hoa sinh 2 phan 1 958

TRƯỜNG ĐẠI HỌC VÕ TRƯỜNG TOẢN KHOA DƯỢC  BÀI GIẢNG MƠN HỌC HĨA SINH Đơn vị biên soạn: XÁC NHẬN CỦA BCN KHOA DƯỢC Hậu Giang – Năm 2013 MUC LUC Trang Lofi ndi dau Muc luc Chu'o'ng Chuyen hoa glucid Pham Thanh Trang Dai ciTdng Thoai hoa glucose 16 Tdnghdp Chuyen hoa cua cac monosaccarid khac 20 Su* chuyen hoa cua glucose d mot so trang thai 22 Lien quan chuyen hoa cua gluose Van chuyen glucose qua mang te bao 24 Dieu hoa chuyen hoa glucose va glycogen-hoat dong ciia hormon 25 24 va nhffng nhan to khac qua trinh chuyen hoa 26 Roi loan chuyen hoa glucid Chtftfng Chuyen hoa lipid Sir tieu hoa va hap thu lipid thtfc an Tran Thi Tudng Linh 31 31 Suf thoai hoa lipid 32 Suf sinh tdng hop lipid Suf chuyen hoa cholesterol 42 50 Chu'o'ng Chuyen hoa protein va acidaminSinh tong hcfp protein Bien hoa protein Tran Thanh Nhan 59 59 Thoai hoa acid amin 62 Tong hdp acid amin 84 Sinh tdng hdp protein 80 Chu'o'ng Chuyen hoa hemoglobin Sinh tdng hop hemoglobin Tran Thi Tudng Linh 102 102 Thoai hoa hemoglobin 105 Roi loan chuyen hoa hemoglobin 108 Chu'o'ng Chuyen hoa acid nucleic Thoai hoa Tdnghdp Pham Thanh Trang 112 112 114 Benh lien quan den roi loan chuyen hoa nucleotid Chu'o'ng Lien quan va dieu hoa chuyen hoa Lien quan gitfa cac qua trinh chuyen hoa 128 Tran Thanh Nhan 133 138 Dieu hoa chuyen hoa Chufcfng Su* trao doi ntftfc va cac chat dien giai Tran Thi Tudng Linh 150 153 Tran Thi Tudng Linh 159 159 161 Cachedemcuacdthe SU dieu hoa thang bang acid - base ciia cd the R6'i loan thang bang acid - base Chu'o'ng Hoa sinh than va nutfc tieu 146 146 Nude cd the Cac chat vo cd cd the SU trao doi nUdc va cac chat dien giai Chuftfng Thang bang acid - base Cd so hoa ly cua thang bang acid - base 133 163 164 Ngo Kien Due 167 Than 167 Nufdc tieu 172 178 Thuf nghiem tham chuc nang than Chu'o'ng 10 Hoa sinh gan Thanh phan hoa hoc cua gan Cac chuc phan hoa sinh cua gan NhUng xet nghiem hoa sinh he thong gan mat Chu'o'ng 11 Hoa sinh mau Ngo Kien Due 183 183 184 191 Tran Thanh Nhan 196 DaicUdng 196 Tinh chat ly hoa ciia mau Thanh phan hoa hoc ciia mau 196 199 Dap an 210 Tai lieu tham khao 212 CHLfCfNG CHUYEN HOA GLUCID MUC TIEU Viet dUdc sd va xac dinh vai tro ciia nhirng dtfcmg chuyen hoa chinh ciia glucid Neu dtfdc y nghia va moi lien quan giffa dtfdng dutmg phan va chu trinh pentose Neu dtfdc dac diem chuyen hoa glucid d cac mo Trinh bay dtfdc cac qua trinh tdng hdp glucid cd the Trinh bay dtfdc chuyen hoa ciia frutose, galactose, mannose Trinh bay dtfdc chuyen hoa ciia glucid cac trtfdng hdp sau an, doi Trinh bay dtfdc su* dieu hoa va nhtfng roi loan ciiachuyen hoa glucid l.DAICl/CfNG Chuyen hoa glucid la mot nhirng qua trinh chuyen hoa quan trong cd the song, chii yeu nham cung cap nang Itfdng cho te bao hoat dong Ngoai stf chuyen hoa cung cap nhieu san pham chuyen hoa trung gian quan Qua trinh chuyen hoa glucid co lien quan chat che vdi su" chuyen hoa cac chat khac cd the, nhat la do'i vdi chuyen hoa lipid, acid amin va acid nucleic Nhu cau glucid ciia ngtfdi trtfdng la 300 - 500g 24h Khi tang Itfdng lipid va protid khau phan an thi nhu cau glucid co the giam thap Trong cd the ngtfdi va dong vatcao cap, glucid ton tai dUdi dang: - Dang du" trtf la glycogen, tap trung chu yeu d gan va cd - Dang van chuyen la glucose ttf mau va cacdich ciia cd the - Dang tham gia cau tao 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 cac hat ngu coc, cii Glycogen: co cac to chtfc va cd dong vat Cellulose: co rau va mot so'qua Cac disaccarid: thtfdng gap la saccarose (dtfcmg mia), lactose (dtfdng sira), maltose (mach nha) Cac monosaccarid co 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 cac monosccarid Enzym thuy phan tinh bot va glycogen la amylase ciia nUdc bot va dich Cd hai loai amylase la aamylase va (3-amylase p-amylase cd mot so thUc vat, a-amylase co 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 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 oligosaccaridase ciia mot non Cac disaccarid 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 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 hap thu ciia cac monosaccarid: galactose(HO) > glucose (100) > fructose (43) > mannose (19) > pentose (15-19) Stf hap thu cd cd che: (1) stf kkuech tan dctn gian, phu thuoc vao gradient ndng cua monosaccarid giffa te bao mang ruot va mau; (2) stfvan chuyen tich ctfc, khong phu thuoc vao gradient ndng ma phu thuoc vao nang Itfdng cung cap, cd che' xay 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 ciia cac cation dac bietla K+ lam tang lap thu glucose Stf hap thu cac hexose tdi tfu nhat 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 cd the iguon carbohydrat nho la galactose, mannose va pentose, nhtfng chat cd kha nang chuyen glucose Ngoai cd the c6n cd nhirng phan khong phai carbohydrat cd kha nang tao glucose nhtf: (1) cac acid amin dtfdc xem la mot nhtfng nguon nguyen lieu de tdng hdp carbohydrat (2) lipid, cdc acid beo khong cd kha nang chuyen 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 C02 va H20 (dtfdng pyruvat), qua trinh xay 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, vtfdt gidi han ltfdng glucose thiia se dtfdc chuyen acid beo a dtf trtf dtfdi dang triglycerid 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 mucopolysaccharid va glycoprotein) - Glucuronic acid (tham gia cac phan tfng khtf doc -detoxication) - Galactose (trong phan ciia glycolipid va lactose) phan ciia cac - Sir dung tdng hdp acid beo va acid amin (1) Cd nhieu acid amin khong cd khau phan an nhtfng van xuat hien phan protein ciia mo cd the, la nhtfng acid amin cd the ttf tdng hdp Cacacid amin dtfdc tdng hdp ttf khung carbon la glucose hay chat chuyen hoa ciia glucose (2) Qua trinh chuyen glucose acid beo xay vtfdt qua gidi han dtf trtf d dang glycogen THOAI HOA GLUCOSE Trong te bao ciia cac to chtfc, glucose ttf dtfdc tao mot phan thoai hoa glycogen (it) hoac tebao lay ttf mau ngoai bien vao Glucose chi cd the di vao dtfdng thoai hoa no 6" dang glucose-6-phosphat Ttf glucose-6-phosphat cd the theo nhieu 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 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 dtfdng dtfdng phan la phan tfng phosphoryl hda glucose 6* C-6 bdi hexokinase Tie'p theo glucose-6-phosphat dtfdc isome hda 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 phan ttf ATP va stf hien dien ciia Mg""" Dtfdi tac dung ciia aldolase, fructose 1,6-diphosphat bi phan doi hai manh3C la glyceraldehyd-3-phosphat (G3P) va dihydroxyaceton phosphat (DHAP) Chi cd G3P tie'p tuc thoai hda Stf can bang phan hai loai triose-phosphat dtfdc dieu khiIn bdi triosephosphat isomerase do ca triose ttf hexose deu cd the dtfdc stf dung hoan toan Mat khac dihydroxyaceton phosphat cd the chuyen hda theo dtfdng khac, la cd stf hien dien DPNH enzym glycerophosphat dehydrogensase se khii dihydroxyaceton phosphat glycerol cung cap cho tdng hdp lipid (hinh 1.1) ©Phosphoryl hoa Hexokinase ©Isomer hoa Glucose-e-phosphat Phosphoglucoisomerase OCH, /-» ©Phosphoryl hoa CH,OH OH Fructose- e-phosphat Phosphofructokinase ©Phan doi Fructose-1 >6-diphosphat Aldolase DHAP ©Isomer hoa CH20 Trios e phosphat isomerase c=o H U CHOH CHpOI Dihydroxyaceton phosphat CH20 Glyceraldehyd-3-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 tao mot NADH H+, dieu kien hie'u NADH H+ se di vao chuoi ho hap te bad tao ATP 1,3-diphophoglycerat cd xu litfdng chuyen nhdm acyl-phosphat cho ADP de tao ATP va phan tfng xiic tac bdi phosphoglyceratkinase Den thdi diem tdng so' ATP tao bdi dtfdng glycolysis la Con dtfdng glycolysis that stf cho nang ltfdng d cac phan irng 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 CH20

G3P Glyceraldehyd-3- phosphat © Oxi hoa va phosphoryl hoa Glyceraldehyd- 3-Phosphat o II dehydrogenase CH20 CHOH DPG © Phosphoryl hoa 1.3-diphosphoglycerat d mufc chat nen Phosphoglycerat kinase coo' CHOH 3PG CH20 3- phosphoglycerat © Isome hoa Phosphoglycerat mutase coo CH—0 2PG CH,OH © Dehydrat hoa 2- phosphoglycerat Enolase coo C—Ow PEP CH2 Phosphoenolpyruvat Phosphoryl hoa d mufc chat nen Pyruvat kinase coo I c=o Pyruvat I CH, Pyruvat Hinh 1.2 Dtfdng phan-glycolysis 2.1.2 Chuyen hda tiep tuc cua acid pyruvic Trong dieu kien hieu Trong dieu kien te'bao cua to chtfc dtfdc cung cap du oxy, acid pyruvic se dtfdc chuen vao ty the, d nd bi khuf carboxyl oxy hda acetyl CoA Sau 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 la mot chuoi phan tfng dtfdc xiic tac bdi mot phtfc hdp da enzym, phtfc hdp co stf tham gia ciia cac coenzym: thiamin pyrophosphat, NAD, FAD K CH3COCOOH + acid pyruvic Mg2+ |)Lipoic Xipoic J^ •»> S lpp CH3CO^s |>ipoic l/Lipoic + CO Hs CH3COWS Hs J/Lipoic + CoA-SH ^- Xipoic HS + CH3COVW S-CoA HSX FAD \f FADH2 NADH? NAD S JyLipoic S Trong dieu kien yem Trong trtfdng hdp co cd yem khi cd van dong ctfdng cao hay d nhtfng vi khuan lactic >6ng dieu kien khong cd oxy, acid pyruvic bi khtf 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 etanol pyruvat ^OOH decarboxylase H 0=0 "^ I CH3 Acid pyruvic A *" CO2 c=o I CH3 Acetaldehyd alcol dehydrogenase /^-^ * ./ , x NADHH+ NAD+ fH2OH ' CH3 Etanol 2.1.3 Nang Itffing tao qua qua trinh thoai hda glucose theo duffing duffing phan Qua trinh thoai hda glucose theo dtfdng dtfdng phan chii ye'u nham cung cap nang Itfdng cho te' bao hoat dong Nang Itfdng tao dtfdc tap trung vao cac lien ket phosphat giau nang ltfdng phan ttf ATP Glycogen Glucose ATP Glucose-1 -â vADP Glucose-6-â Fructose-6-â ATP i ADP Fructose-1,6-diđ Dihydroxyaceton-â Glyceraldehyd- 3-© —I I Glycerol- © Glycerol + t NADHH+(x2) 1,3- diâ glyceric acid *ã ADP ->+ATP(x2) 3- â glyceric acid \ 2- © glyceric acid 2-© enolglycene I ^-—AD? |ieu la c*c mononucleotid ttfdng tfngenzyn xuctac ARN polymease h ADN ,ARNm dtfdcdoisinhbaztode'ngtao** ™^ ^ C i trinh philn tuan theo quy luat nen phan ttf lai AKlNm Nh, vay cac thdng tin aADN vlcau trtfc cua protein^ =^-de, da dtfdc^yen sang ARNm va ARNm dtfdc coi nhtf "°