Bg hoa sinh 2 phan 1 958

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 carbohydra

TRƯỜNG ĐẠI HỌC VÕ TRƯỜNG TOẢN

Lofi ndi dau

4 Chuyen hoa cua cac monosaccarid khac

5 Su* chuyen hoa cua glucose d mot so trang thai

6 Lien quan chuyen hoa cua gluose

7 Van chuyen glucose qua mang te bao

8 Dieu hoa chuyen hoa glucose va glycogen-hoat dong ciia hormon

va nhffng nhan to khac trong qua trinh chuyen hoa

9 Roi loan chuyen hoa glucid

Trang

Pham Thanh Trang

Tran Thi Tudng Linh

Tran Thanh Nhan

1 2

4 4 6 16 20 22 24 24 25

26

31 31 32 42 50

Chtftfng 2 Chuyen hoa lipid

1 Sir tieu hoa va hap thu lipid trong thtfc an

2 Suf thoai hoa lipid

3 Suf sinh tdng hop lipid

4 Suf chuyen hoa cholesterol

Chu'o'ng 3 Chuyen hoa protein va acid

amin-Sinh tong hcfp protein

1 Bien hoa protein

2 Thoai hoa acid amin

3 Tong hdp acid amin

4 Sinh tdng hdp protein

Chu'o'ng 4 Chuyen hoa hemoglobin

1 Sinh tdng hop hemoglobin

2 Thoai hoa hemoglobin

3 Roi loan chuyen hoa hemoglobin

Chu'o'ng 5 Chuyen hoa acid nucleic

1 Thoai hoa

2 Tdnghdp

Tran Thi Tudng Linh

59 59

62

84 80

102 102 105 108

112 112 114

Pham Thanh Trang

3 Benh lien quan den roi loan chuyen hoa nucleotid 128

Chu'o'ng 6 Lien quan va dieu hoa chuyen hoa

1 Lien quan gitfa cac qua trinh chuyen hoa

2 Dieu hoa chuyen hoa

Chufcfng 7 Su* trao doi ntftfc va cac chat dien giai

1 Nude trong cd the

2 Cac chat vo cd trong cd the

3 SU trao doi nUdc va cac chat dien giai

Chuftfng 8 Thang bang acid - base

1 Cd so hoa ly cua thang bang acid - base

2 Cachedemcuacdthe

3 SU dieu hoa thang bang acid - base ciia cd the

4 R6'i loan thang bang acid - base

Chu'o'ng 9 Hoa sinh than va nutfc tieu

1 Than

2 Nufdc tieu

3 Thuf nghiem tham do chuc nang than

Chu'o'ng 10 Hoa sinh gan

1 Thanh phan hoa hoc cua gan

2 Cac chuc phan hoa sinh cua gan

3 NhUng xet nghiem hoa sinh he thong gan mat

Chu'o'ng 11 Hoa sinh mau

1 DaicUdng

2 Tinh chat ly hoa ciia mau

3 Thanh phan hoa hoc ciia mau

Dap an

Tai lieu tham khao

Tran Thanh Nhan 133

133 138

Tran Thi Tudng Linh 146

146 150

153

Tran Thi Tudng Linh 159

159 161

163

164

167 172

178

183 184

191

Tran Thanh Nhan 196

196 196

199 210 212

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 vat cao 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 cac dich 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-a-amylase p-a-amylase cd trong mot so thUc vat, a-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

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 biet la 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 chuyenthanh 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 Cac acid 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 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)

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 giaidoan 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)

2 G3P

© Oxi hoa va phosphoryl hoa

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

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-OHCHj NADHH+ NAD+ CH3

Acid pyruvic Acid lactic

Trong qua trinh len men rtfdu, acid pyruvic bi khir thanh etanol.

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 nangItfdng cho te' bao hoat dong

Nang Itfdng tao ra dtfdc tap trung vao cac lien ket phosphat giau nang ltfdng trong phan ttf

ATP.

Glucose-1 -©

Glucose

vADPGlucose-6-©

Hinh 1.3 Nang ltfdng tao ra qua qua trinh thoai hda glucose theo con dtfdng dtfdng phan.

Trong dieu kien hie'u khi cd du oxy, 1 phan tu" glucose thoai hda hoan toan se cho 26 ATP

va 4 NADH2 (# 12 ATP) = 38 ATP Neu ttf glucose cua glycogen la 39 ATP.

Qua tinh toan tren ta tha'y thoai hda glucose mot each hoan toan den C02 va H20 (nghia la

cd stf ket hdp vdi chu trinh citric va chudi oxy hda krrtf te' bao) se cung cap mot ltfdng ldn nang

ltfdng dtfdi dang ATP cho te bao.

Tuy nhien stf thoai hda glucose bang con dtfdng dtfdng phan trong dieu kien ye'm khi (san

pham tao thanh la acid lactic) cung cd y nghia ve phtfdng dien nang ltfdng, bdi vi tuy nd tao itATP, song san pham thu dtfdc la acid lactic se dtfdc cd the stfdung lai de tai tao glucose cho quatrinh thoai hda tiep theo Vi vay con dtfdng nay van dong vai trd quan trong ve phtfdng dien cungcap nang Itfdng (dac biet la to' chtfc cd khi cd hoatdong)

-+ ATP (x 2)

+ 12 ATP ( x 2)

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).

Hinh 1.4b Chu trinh Cori.

2.1.5 Dufing pMn (glycolysis) o* hong diu

O hong cau san pham cuo'i cung ciia con dtfdng dtfdng phan la lactat Vi d hong cau

khong cd ty the, NADH dtfdc tao ra bdi glyceraldehyd phosphat dehydrogenase khong the bi oxyhda trong chuoi ho hap va do do tie'p tuc phan tfng vdi pyruvat tao lactat va NAD+ NAD+ tie'ptuc dtfdc stf dung trong con dtfdng dtfdng phan (hinh 1.5) G

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 d cd 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.

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 3phan ttf C02 va 3 phan tuf pentose phosphat, tie'p theo la mot chuoi phan tfng bien doi de 3 phanttf pentose phospphat tren tao thanh 2 phan ttf glucose-6-phosphat va mot phan ttf

M» W^-"^^^ su thoai hoa tiep nhCmg san

phosphat, fructose-6-phosphat, fructose-l,6-diphosphat (hinh 1.7).

Glycogen Glucose

dihydroxyaceton-® glyceraldehyd-©

Pyruvic

NADH H+

Ribulose5P Xylulose 5P

acid nucleic

Ribose5P

ffinh 1.7 M6'i Hen quan giffa con Al8ng glycolysis va hexose monophosphat.

v<5i mot so' thuo'c d! dao thai qua nUdc t,eu hay mat c6

cd the' thoai hda tie'p tuc trong chu trinh pentose (hinh 1.8).

H OH

a UDP glucuronic

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 phantfng cat nhanh va cat lien ket a-l-»6, (3) phosphoglucomutase chuyen glucose-1-phosphat thanhglucose-6-phosphat, (4) glucose-6-phosphatase chuyen glucose-6-phosphat thanh glucose (hinh

Glucose 6jphosphatase Phosphoglucomutase

Hinh 1.10 Thuy phan glycogen (glycogenosis).

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)

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 theglycogen dtf trtf chii ye'u d gan va cd, ty le cao nhat d gan 2%-8% Cd chtfa l%-3% glycogennhtfng 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 laynguon 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 vaphosphorylase 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

TOfSN

twcvd tRddHQ

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)

C

O ,UDP Bo$n glycogen Glcn Glycogensynthase

UDP

c

Glycogen

Glc::r <olxz>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

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).

4 CHUYEN HOA CUA CAC MONOSACCARID KHAC

Trong thtfc an cd ba hexose chinh khac ngoai glucose dtfdc cd the hap thu va su" dung la

galactose, fructose va mannose (hinh 1.15)

Hinh 1.15 Sir dung galactose, fructose, mannose. *

4.1 Stf suf dung galactose

Nguon D-galactose chii ye'u ttf stf thuy phan lactose co nhieu trong stfa Con dtfdng chinh

de sir dung galactose la qua trinh chuyen thanh glucose-6-phosphat de tiep tuc thodi hoa bang

con dudng dtfdng phan Qua trinh chuyen galactose thanh glucose-6-phosphat gdm 4 phan tfng

UDP_Gal epimerase •

Hinh 1.16 Chuyen galactose thanh glucose-6-phosphat.

O tuyen vii trong thdi ky hoat dong cac enzym tham gia trong qua trinh tren cung cd mat

trong qua trinh tong hop lactose Lactose dtfdc tao ttf stf ket hdp UDP-galactose va glucose dtfdi

tac dung ciia lactose synthase

Trong cd the galactose khong chi can cho qua trinh tdng hdp lactose ma con tham gia vaoqua trinh tdng hdp glycolipid, glycoprotein va proteoglycan

d ngtfdi benh cd tinh di truyen la galactose huye't bam sinh (galactosemia) do thieu

enzym UDP-glucose-galactose- uridyltransferase, benh gay stf tich tu galactose va

galactose-1-phosphat trong mau va mo vdi trieu chtfng lam sang nhtf cham phat trien tri nao, due thuy tinhthe, gan to Benh gap d tre sd sinh khi bat dau dung stfa cd lactose Phai cho tre ngtfng stfa.

4.2 Stf stf dung fructose

Fructose cd nhieu trong trai cay va la san pham thuy phan ciia sucrose (dtfdng mia) Quatrinh phosphoryl hda fructose xay ra d hau het cac mo va cho fructose-6-phosphat, san phamtrung gian ciia con dtfdng dtfdng phan Ben canh qua trinh tren con co mot con dtfdng phu

chuyen fructose thanh fructose-1-phosphat bdi enzym fructokinase cd nhieu d gan, than va ruot,

fructose-1-phosphat tiep tuc bi phan doi cho dihydroxyaceton phosphat (tham gia tdng hdp

glycerol) va D-glyceraldehyd dtfdi tac dung ciia aldolase B (hinh 1.15) Qua con dtfdng phu nay

cho tha'y trong che do an cho nhieu fructose (nhtf trai cay, dtfdng mia, bia ) thi tang tdng hdp

cho acid beo, VLDL do do cd the gay tang triacylglycerol va LDL cholesterol mau

4.3 Su* stf dung mannose

Mannose cd nhieu trong san pham tieu hoa ciia cac loai thtfc an cd chtfa nhieu

polysaccarid hay glycoprotein Sau khi dtfdc hap thu mannose phosphoryl hda cho

mannose-6-phosphat va sau do tie'p tuc dtfdc isomer hda cho fructose-6-mannose-6-phosphat (hinh 1.15)

5 SlJ CHUYEN HOA CUA GLUCOSE 6 M0T SO TRANG THAI

5.1 d trang thai sau khi hap thu glucose tti he thong tieu hda (Fed state)

Carbohydrat sau khi qua qua trinh thuy giai d he thong tieu hda cho monosaccarid cd

thanh phan chii yeu la glucose Monosaccarid sau khi hap thu qua ruot se den gan va cd O gan

glucsose bi oxy hoa den C02 va H20 mot phan khac tham gia tdng hdp glycogen va triacylglycerol dtfa den mo md de dtf trtf 6 cd gluose bi oxy hoa de'n C02 va H20 de cung cap ATP va tham gia tdng hdp glycogen ciia cd Mot phan glucose de'n mo md de tdng hdp

triacylglycerol Khi de'n nao thi chii yeu glucose bi oxy hoa den C02 va H20 de cung cap ATP

5.2 6 trang thai doi (Fasting state)

Khi cd the dong vat thieu thtfc an, cd the cd nhu cau cap thiet ve stf duy tri ndng do glucose trong mau vi ndng do glucose dang giam dtfdi gidi han (khoang 2,5 mM dngtfdi) va gay

roi loan he thin kinh trung tfdng 6 ngtfdi la bie'u 16 cua trieu chtfng cua ha dtfdng huye't trong

mau nhtf hoat dong cd ye'u va khong pho'i hdp, rd'i loan nhan thtfc va &6 md hoi Ne'u ndng d6

glucose tie'p tuc giam se dan de'n tinh trang hon me.

Nguon cung cap glucose mau cap thiet la nguon glycogen dtf trtf ciia gan Trong vong vai giay ltfdng glycogen ciia gan cd the thuy giai cung cap glucose dtfa vao mau, qua trinh nay la qua trinh thuy giai glucose (glycogenosis) Glycogen cua cd chtfa mot ltfdng ldn glucose dtf trtf nhtfng nd khong trtfc tie'p cung cap glucose cho mau Mac dtf glycogen ciia gan la nguon cung

cap glucose cap thiet nhtfng gan cd the lap ttfc san xuat glucose bang qua trinh tong hdp mdi glucose ttf acid amin ciia cd (acid amin dtfdc phdng thich ttf cd va chuyen tdi gan de tdng hdp glucose)- qua trinh gluconeogenesis Cung luc nay qua trinh ketogenesis bat dau, qua trinh nay xay ra dgan va chuyen acid cid beo dtfdc phdng thich ttf mo md thanh the ceton de cung cap cho

cac mo nham tranh qua trinh sir dung qua mtfc glucose Qua trinh phdng thich acid beo ttf dang dtf trtf la triacylglycerol trong mo md goi la qua trinh lipolysis Qua trinh nay xay ra vdi stf dieu

khien cua cac hormon Adrenalin va glucagon kich hoat enzym phdng thich glucose ttf glycogen ciia gan Glucagon cung hoat hda qua trinh tdng hdp mdi glucose (gluconeogenesis) Cac glucocrticoid hoat hda qua trinh giai phdng acid amin ttf cd Adrenalin va adrenocorticotropin

(ACTH) va hormon tang trtfdng se hoat hda qua trinh lipolysis (hinh 1.18).

Tranq thai do

Glycogen,

Acid beo A

6 LIEN QUAN CHUYEN HOA CUA GLUCOSE

Hinh 1.19 Lien quan chuyen hda ciia glucose.

7 VAN CHUYEN GLUCOSE QUA MANG TE BAO

Mot trong nhtfng giai doan quan trong nhat ttrong chuyen hoa glucose la van chuyen

glucose qua mang te'bao Glucose dtfdc van chuyen vao te'bao bdi cac tac nhan van chuyen Cd

nam tac nhan van chuydn glucose dtfdc tim tha'y la GLUTl, GLUT2, GLUT3, GLUT4 va GLUT5

va sau day la stfphan bo'ciia cac tac nhan van chuyen nay (Bang 1.1)

Bang 1.1 Cac tac nhan van chuyen glucose qua mang te'bao

Tac nhan van

Hau nhtf duy nhat cd d te bao than kinh (nao), cdciia bao thai

Mo nhay cam vdi insulin (nhtf cd xtfdng, cd tim, mo md)

Mang ruot, tinh dich, cd xtfdng, mo md La tac nhan van chuyen cho

fructose va ca glucose.

GLUT 2

Glucose Glucose 6 _phosph at

Glucokinase

Glycogen

Hinh 1.20 Van chuyen glucose ciia GLUT2

8 DIEU HOA CHUYEN HOA GLUCOSE VA GLYCOGEN-HOAT DONG CUA

HORMON VA NHtfNG NHAN TO KHAC TRONG QUA TRINH CHUYEN HOA

Binh thtfdng glucose mau 0,7 - 1,2 g/L hay 70-120 mg% hay 4,22 - 6,67mmol/L Dtfdnghuyet luon luon on dinh nhd stf can bang gitfa nguon cung cap va ltfdng stf dung

Nguon cung cap glucose vao mau nhtf nguon glucid ngoai sinh ttf thtfc an, nguon noi sinh

do phan giai glycogen va tan tao glucose d khoang gitfa cac budi an

Sir dung glucose d cac td chtfc nhat la mo cd, mo than kinh, mo md Sir dung glucose de tdng hdp dang dtf trtf d tat ca cac td chtfc va nhieu nhat d gan va cd.

Dieu khien chinh cac qua trinh chuyen hoa ciia carbohydrat la cac hormon

Khi cd the d trang thai sau budi an, ltfdng ldn carbohydrat chii yeu la glucose dtfdc hap thu ttf ruot (3 trang thai nay insulin la tac nhan chinh dieu khien qua trinh chuyen hda ciia

glucose Hoat dong chinh ciia insulin la gia tang qua trinh tdng hdp glycogen (glycogenosis) dgan va cd ttf nguon glucose va dong thdi cung gia tang qua trinh tdng hdp triacylglycerol d gan

va mo md (dac biet la khi mot ltfdng ldn glucose dtfdc hap thu)

Ngtfdc lai d trang thai doi hay xa btfa an hoat dong ciia insulin giam di, tac nhan chinh dieu khien cac qua trinh chuyen hda glucose liic nay la cac hormon nhtf glucagon,

glucocorticoid, adrenalin, ACTH (adrenocorticotropin), hormon tdng trtfdng Vi ltfdng glycogen

ciia gan cd gidi han nen de dap tfng nhu cau glucose ciia cd the trong liic nay cd the phai sir

dung nguon acid amin ttf qua trinh thuy phan protein ciia cd de tan tao glucose Khi do cd su*dung nguon nguyen lieu de thoai hoa cho nang Itfdng la cac the ceton ttf stf thuy phan acid beo

jiia mo md thay the' cho glucose Do do khi cd the trong tinh trang doi keo dai cd rat can thiet

ho stf song (nguon cung cap glucose ).

Insulin

Do te bao dao p Langerhans ciia tuyen tuy Insulin lam giam glucose mau do: (1) Lam

tang stf stf dung glucose d tat ca cac md nhat la te bao cd, xtfdng, tim va mo md bang each tdng

hoat dong GLUT4 van chuyen glucose qua mang te' bao va being each kich thich sinh tdng hop

cac enzym chinh ciia con dtfdng dtfdng phan (glycolysis) (2) Tang tdng hdp glycogen bang each tdng hoat glycogen synthase (3) Giam stf phan ly glycogen d gan, cd (hinh 1.20).

Ngoai ra insulin con lam tdng qua trinh stf dung glucose de tdng hdp acid beo va lipid dtf

trtf d mo md va tfc che cac hormon gay tdng glucose mau.

Ngoai te bao Trong te bao

Stf co cd hay kich thich than kinh khien tuy thtfdng than giai phdng adrenalin, adrenalin

kich thich gan phan giai glycogen vao mau va kich thich cd phan giai glycogen cung cap nang

ltfdng cho cd hoat dong.

Thyroxin

Hormon tuyen giap, lam tang glucose mau do: (1) tang hap thu glucose d ruot (2) tang

phan ly glycogen d gan

Glucocorticoid

Hormon vo thtfdng than, lam tang dtfdng huyet bang each: (1) tang hap thu glucose &mot

(2) tang tan tao glucose (gluconeogenesis) (3) tang phan ly glycogen (4) tfc che' tieu dung

glucose d cac mo ngoai gan

Hormon tang tntdng

Hormn tuyen yen trtfdc lam tang dtfdng huyet do giam tdng hdp va tang phan glycogen,

giam stf tham glucose vao cac mo

ACTH

ACTH kich thich vo thtfdng than tiet hormon steroid trong do co glucocorticoid

9 ROI LOAN CHUYEN HOA GLUCID

9.1 Benh tieu dUbng tuy

Cd hai dang tieu dtfdng tuy: (1) Dang 1 (type 1), con dtfdc goi la typ tre vi xay ra d tre em

va ngtfdi nho tudi (2) Dang 2(type 2) xay ra d ngtfdi ldn tudi va dac biet cd the trang map.

D6'i vdi typ 1te bao p ciia dao Langerhans tuy khong cd kha nang tiet isulin do do phtfdng

phap dieu tri la bd sung isulin Nguyen nhan gay tieu dtfdng typ 1do he thong mien dich ciia cd

the ttf tao khang the tan cong te'bao p

Doi vdi typ 2, du mot ltfOng dang ke isulin dtfdc tiet ra nhtfng khong duy tri dtfdc ndng do glucose dmtfc binh thtfdng Nguyen nhan chtfa dtfdc biet ro nhtfng trong mot so trtfdng hdp la do

te bao dich ciia khong dap tfng vdi insulin Do do phtfdng phap didu tri trong tieu dtfdng typ 2la

dieu chinh ch£ dp an thich hdp va dimg dtfdc pham kich thich tang tiet isulin cua te bao tuy.

Dac diem d ngtfdi tieu dtfdng tuy:

- Ndng do glucose trong mau tang.

- Tang the ceton va acid beo ttf do trong mau

- Mat muo'i.

- Tang ltfdng ntfdc tieu, tang ure

- Mo va te bao doi nang ltfdng

Nguyen nhan (hinh 1.22)

Do thie'u insulin, kha nang van chuyen glucose qua mang te' bao bi giam va qua trinh

phosphoryl hda glucose bi giam Ndng do glucose tang cao d khu vuc ngoai te bao nhtf mau va

dich gian bao, trong khi te bao khong cd glucose de chuyen hda nen lam vao tinh trang doi nang

ltfdng te bao Te bao phai tang ctfdng thoai hda cac cd chat khac, nhat la lipid Acid beo dtfdcgiai phdng ttf mo md.

Qua trinh thoai hda lipid cu the la cac acid beo, se tao nhieu acetyl CoA Nhtfng acetyl

CoA tien lai khong dtfdc oxy hda net trong chu trinh acid citric vi thie'u oxaloacetic (san pham

dtfdc tao ra chii ye'u bdi acid pyruvic cua hda trinh thoai hda glucose) Acetyl CoA se bi if dong

lai, chuyen hda theo htfdng tao the cetonic, chat nay dtfdc dao thai qua dtfdng tieu va hdi thd Vi

tang dao thai the ceton trong ntfdc tieu se ke't hdp vdi tang thai muo'i

Glucose dtfdc dao thai trong ntfdc tieu lam tang ap Itfc tham thau-nen keo theo tang dao thai ntfdc qua than Do do benh tieu dtfdng thtfdng kern theo roi loan chuyen hda lipid va cac

chuyen hda khac ciia cd the nhtf trao ddi muo'i ntfdc, can bang acid base.

Tinh trang ddi nang ltfdng trong te bao ciia cac cd quan se dan de'n roi loan chtfc nang va thoai hda cac cdquan do nhtf: due thuy tinh the, ton thtfdng he thong mach mau, suy giam miendich, nhiem khuan

bi h, 8tMI «*» «« M» «l»y =4 "kI"« «" h»" m' " M°°e y"'

RUQt

Na° Khong co glucose ttf he tieu hoa

Glucose ft

Insulin tic che hormon

cua cac qua trinh

•°~ Mo m3

Hinh 1.23 Ket qua cua tang tiet insulin.

^ "i^^TSt£Lu enzym ga,actose uridyl transferase ngn galactose khdng

du* S^uc^ trong gan gjsuy gan co tf* gay *vong Phai cho tre ngtfng s,a

me thay the bang stfa khong cd lactose.

Mm6n Hda sinh-Tr^ng Dai hoc Yha Noi Hda sinh NXB ^^2°^

2 B6 mon Hoa sinh -Dai hoc Ydtfdc TPHCM, Hoa smh yhoc NXB Yhoc TP HCM 2003.

3B6 YTe' Vu Khoa hoc va Dao tao, Hda sinh hoc, NXB Yhoc Ha No., 2005

4VJL LDavison, Donald b Sittman, Biochemistry, 3*edition Harwa, Pubhsh.ng, 994.

5;,,Campbe,Bioche^

6 Robert K Murray, Daryl K Granner, Victor w kuu , r

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

CAUHOITlTLLfCfNGGlA

Chon mot hay nhieu cau diing

1 Vitamin nao cd anh htfdng nhieu trong qua trinh ha'p thu va chuydn hda glucid

a BI

b B6

c B12

d C

2 Tap hdp cac phan tfng nao sau day sinh ATP trtfc tie'p

PGA-f*M'3diP Glycerat-^ 3p Glycerat -3** 2P Glycerat -^ PEP-j*-Pyruvat

4 San pham thoai hda cuoi cung ciia glucose theo con dtfdng dtfdng phan

a Xay ra d hong cau la Lactat

b Xay ra d hong cau la Pyruvat

c Xay ra d te bao cd trong dieu kien yem khi la Pyruvat

d Xay ra d te bao cd trong dieu kien yem khi la Lactat

5 O benh nhan tieu dtfdng tuy, do thie'u Isulin nen:

a Giam hoat dong glycogen synthase

b Tang hoat dong GLUT4

c Tang hoat hexokinase

d Giam tdng hdp cac enzym chinh ciia con dtfdng glycolysis

6 Cac hormon nao sau day lam tang qua trinh thuy giai glycogen d gan

a Hong cau thie'u NADPH

b Hong cau thie'u glutathion dang khtf

c Hong cau thie'u glutathion dang oxy hda

d Hong cau khong phan huy dtfdc cac goc oxy hda

9 San pham nao sau day ciia con dtfdng phan cd the tdng hdp cho lipid

a G3P

b DHAP

c DPG

d 1,3DPG

10 Tac dong de lam giam glucose mau ciia Isnulin

a Tang hoat glycogen synthase

b Tang hoat dong GLUT4

c Tang hoat hexokinase

d Tang tdng hdp cac enzym chinh ciia con dtfdng glycolysis

11 Khi cd thd dong vat dtrang thai ddi, de cung cap nham duy tri ndng do glucose cho mau thi

cac qua trinh nao sau day xay ra:

a Tang thuy giai glycogen ciia gan

b Tang thuy giai triacylglycerol

c Tang qua trinh tan tao glucose ttf acid amin

d Tang thuy giai glycogen ciia cd

12 Glycogen ciia cd khong la nguon dtf trtf cho toan cd the vi cd thieu enzym

a Phosphorylase

b Phosphoglucomutase

c Glucose 6 phosphatase

d Glucano transferase

CHUCfNG 2

CHUYEN HOA LIPID

MUC TBEU

1 Neu dtfdc tien trinh, cd che ciia phan tfng thuy phan va stf hap thu ciia cac hdp chat lipid.

2 Trinh bay va giai thich dtfdc tien trinh, cd che ciia stf thoai hda lipid.

3 Neu va giai thich dtfdc tien trinh, cd che'ciia stf sinh tdng hdp lipid.

4 Trinh bay va giai thich dtfdc tien trinh, cd che ciia stf sinh tong hdp va thoai hda cholesterol.

Cung nhtf glucid va protid, lipid la thanh phan cd ban ciia sinh vat

d cac ntfdc cong nghiep phat trien, >40% nhu cau ve nang ltfdng dtfdc cung cap bdi

triglycerid ttf thtfc an Triglycerid cung cap hdn Vi nhu cau ve nang ltfdng ciia mot sd' cd quan,

dac biet la gan, tim, va mo xtfdng

Ve mat sinh ly lipid cd the chia thanh hai loai:

Lipid dtf trtf: chu yeu la triglycerid, ton tai trong cd the vdi ltfdng thay doi Lipid dtf trtf dtfdc

tao thanh mot phan do thtfc an, mot phan cd nguon goc noi sinh do qua trinh tdng hdp ttf glucid

hay protid Khi ddi, cd the ngtfdi va dong vat stf dung md dtf trtf ttf cac te bao md.

Lipid cau tao (lipid mang): chii ye'u la phospholipid va cholesterol; la thanh phan khong thay

ddi, chiem khoang 10% trong ltfdng kho ciia cac td chtfc.

Nhtfng nghien ctfu ve chuyen hda lipid da xac dinh lipid cd hai chtfc nang chinh la san sinh nang

Itfdng va xay dtfng cau true te' bao va mo Ngoai ra, mot so' lipid phtfc tap con gitf cac vai tro quan trong nhtf cd lien quan den dac tinh ciia mang te bao, kha nang hoa tan ciia nhtfng chat

khong phan ctfc trong cac dich ciia cd the; cac hormon steroid va prostaglandin gitf vai tro sinh lydac biet trong viec dieu hoa qua trinh chuyen hda

1 SI/ TIEU HOA VA HAP THU LIPID TRONG THtfC AN

1.1 Su* tieu hoa lipid

1.1.1 Stf thuy pMn triglycerid (triacylglycerol)

Triglycerid la chat tieu bieu ciia lipid ddn gian cd trong thtfc an goi la chat beo

Stf tieu hda lipid thtfc chat la stf thuy phan triglycerid xay ra theo ttfng giai doan d hanh

a trang nhd tac dung ciia enzym lipase cung vdi stf tham gia ciia cac tac nhan nhu ttfdng hda lamat va muo'i mat.

Trtfdc khi thuy phan, lipid dtfdc nhu ttfdng hda bdi muo'i mat cd trong dich mat, vi d trang

thai nhu ttfdng lipid cd dien tich tiep xiic ldn, lam tang tac dong ciia lipase va dtfdc phan tan dtfdinhtfng hat nho de cd the khue'eh tan de dang qua mang ruot

Muo'i mat la hdp chat ltfdng ctfc, tac dong nhtf mot chat dien hoat sinh hoc chuyen chat

beo trong thtfc an thanh nhtfng mixen hdn hdp ciia muo'i mat va triglycerid

Lipase la nhtfng enzym ciia hanh ta trang dtfdc tiet ra ttf tuyen tuy, cd tac dung thuy phan lienke't ester ciia acid beo va glycerol

Lipase tach cac acid beo ttf phan tii glycerid vdi toe do khac nhau tuy thuoc vao vi tri ciia

acid beo trong phan tir triglycerid Enzym nay cat mot each dac hieu lien ke't ester 1,3 (a,a ciia

triglycerid nen stf thuy phan lien ke't ester d vi tri 2 (P) can phai co stf dong phan hda de chuyen

lien ke't ester ttf vi tri 2 len vi tri 1.

Triglycerid 1,2 diglycerid 2-monoglycerid 1-monoglycerid glycerol

Hinh 2.1 Sd do ciia stf thuy phan triglycerid.

Stf thuy phan triglycerid khong hoan toan nen tao thanh mot hdn hdp cac san pham trung

gian gdm cd triglycerid, diglycerid, monoglycerid, glycerol va acid beo.

1.1.2 Thuy phan phospholipid

Phospholipid bi thuy phan bdi enzym phospholipase ciia dich tuy Cd nhieu loai

phospholipase, mdi loai thuy phan mot trong cac lien ket ester ciia phan tuf phospholipid: ^

- Phospholipase Al cat lien ket ester ciia chtfc alcol d Ci Enzym nay cd nhieu trong

mang ciia lach, nao, gan va nhieu trong dich tuy

- Phospholipase A2 cat lien ket ester ciia chtfc alcoi d C2 ; enzym nay cd trong noc ran

doc, dich tuy.

- Phosphodiesterase cd trong te bao ruot, cd the cat lien ke't ester gitfa acid phosphoric va cholin, giai phdng cholin va acid glycerophosphatidic hay lien ket ester gitfa acid phosphoric va

glycerol, giai phdng diglycerid va phosphocholin

- Phosphomonoesterase (phosphatase) tiep tuc thuy phan san pham thuy phan ciia phosphodiesterase, nhtf thuy phan phosphocholin giai phdng acid phosphoric va cholin.

1.1.3 Thuy phan sterid

Cholesterol ester (sterid) bi thuy phan bdi enzym cholesterol esterase ciia ruot tao thanh

cholesterol va acid beo.

1.2 Stf ha'p thu lipid

Hdn hdp lipid bi thuy phan chtfa hoan toan dtfdc hap thu qua mang ruot d dang nhQ ttfdng

nhd cac acid mat.

- Glycerol va acid beo mach ngan (< IOC) theo mau de'n gan, chii ye'u qua tinh mach ciia.

Cac acid beo di chuyen trong mau dtfdi dang ket hdp vdi albumin

- Cac acid beo mach dai, mono, diglycerid dtfdc suf dung de tdng hdp lai triglycerid d

mang ruot Cac triglycerid mdi dtfdc tdng hdp nay khuech tan qua mach bach huyet roi vao mau

de van chuyen den gan, cac td chtfc, cd, mo md dtfdi dang nhtfng hat lipoprotein goi la

chylomicron Tai cac td chtfc, phan ldn triglycerid cua chylomicron dtfdc thuy phan bdi

lipoproteinlipase thanh glycerol va acid beo Nhtfng san pham nay se dtfdc chuyen hda tiep tuc d

te bao 6 cd, cac acid beo bi oxy hda de giai phdng nang ltfdng; con d mo md, cac acid beo dtfdc

ester hda trd lai thanh triglycerid dtf trtf Khi khau phan an chtfa nhieu acid beo hdn nhu cau can

cho cd the, triglycerid tdng hdp dgan dtfdc van chuyen vao mau dtfdi dang lipoprotein tdi cac td

chtfc, dac biet la mo md de dtf trtf, va den cd de cung cap nang ltfdng Khi hormon bao hieu cd

the can nang ltfdng, triglycerid trong mo md dtfdc huy dong, thuy phan thanh glycerol va acid

beo dtfdi tac dong ciia enzym lipase nhay cam vdi hormon

2 SI/ THOAI HOA LIPID

2.1 Thoai hda glycerol

nAB

- O H

-OH -OH

Ogan va mot so td chtfc khac, glycerol dtfdc phosphoryl hda thanh glycerol 3-phosphat dtfdi tac

dung ciia enzym glycerolkinase Chat nay sau do dtfdc [O] thanh dihydroxyacetonphosphat

Dihydroxyacetonphosphat dtfdc chuyen thanh glyceraldehyd 3-phosphat dtfdi tac dung ciia enzym triose phosphat isomerase Chat nay tie'p tuc tham gia con dtfdng Embden Meyerhof hay tdng hdp glycogen Mo md khong cd enzym glycerokinase.

CH2OH

HO - C - H I CH2OH

•ATP

Glycerolkinase

ADP

CH2OH I

HO - C - H

*• I

O II

o-H - C -Oo-H O CH2-0-P-0-

Qua trinh thoai hda glucid

Hinh 2.2 Sd do qua trinh thoai hda glycerol.

2.2 Thoai hoa acid beo

2.2.1 Stf oxy hda acid beo bao hoa co so' C cmfn

2.2.1.1 Hoat hoa acid beo va van chuyen vao ty the

Trtfdc khi tham gia vao qua trinh p oxy hda, acid beo dtfdc hoat hda thanh acyl CoA:

nhdm carboxyl ciia acid beo tac dung vdi nhdm thiol ciia CoA de tao thanh mot thioester

Phan tfng hoat hda xay ra d ben ngoai ty the, vdi stf hien dien ciia ATP, Mg2+ va dtfdc xuc tac

bdi enzym acyl CoA synthase (thiokinase)

thiokinase

R-CH,-CH9-C00H + CoASH + ATP ^ R - CH2-CH2 - CO ~ SCOA + AMP + PP

Pyrophosphat dtfdc hinh thanh trong qua trinh phan tfng se lap ttfc bi thuy phan dtfdi tac

dung ciia enzym pyrophosphatase tao thanh orthophosphat:

AMP dtfdc giai phdng trong phan tfng tren se dtfdc phosphoryl hda trd lai:

Vay thtfc chat qua trinh hoat hda mot phan til acid beo da su' dung 2ATP

Cd nhieu loai thiokinase khac nhau ttfdng tfng vdi ttfng loai acid beo ngan hoac dai

Qua trinh p oxy hda xay ra d trong ty the (la ndi co nhieu enzym can thie't cho stf (3 oxy

hda) ma cac acyl CoA khong vtfdt qua dtfdc mang ty the nen phai dtfdc van chuyen vao trong ty

the nhd he thong carnitin cd nhieu trong cd va mo dong vat.

Carnitin la mot amin bac 4, mang mot chtfc alcol bac 2, cd the ester hda vdi acid bee dtfdi

tac dong ciia acylcarnitin transferase I theo phan tfng:

Acyl CoA liic nay mdi bat dau qua trinh p oxy hda.

Nhtfng acid beo mach ngan (< 12C) cd the di chuyen qua ty the ma khong can chat van chuyen

2.2.1.2 Qua trinh p oxy hda

Qua trinh p oxy hda xay ra trong ty the, gdm 4 phan tfng:

Phan tfng oxy hoa ldn 1:

Dtfdc xiic tac bdi enzym acyl CoA dehydrogenase, cd coenzym la FAD, hinh thanh mot

hen ket doi gitfa Ca va Cp, san pham tao thanh la trans -A2 enoyl CoA:

acylCoAdehydrogenase

Acyl CoA FAD FADH , tran.A2 )noy| CoA)

^ Acid beo chtfa bao hoa tao thanh trong giai doan nay cd ca'u true dang trans, trong khi

phan ldn acid beo thien nhien thuoc loai cis

FAD ket hdp vdi 1cap Htach ra ttf Ca va Cp ciia cd chat tao FADH2.

FADH2 tao thanh dtfdc oxy hda trd lai bdi enzym trong chuoi ho hap te bao.

Phan tfng ket hg"p nUdc

Stf ke't hdp ntfdc vao nd'i doi ciia trans -A2- enoyl CoA dtfdc xiic tac bdi enzym enoyl

CoA hydratase (goc OH dtfdc gan vao Cp) tao thanh p-hydroxyacyl CoA:

R PH ru nr\ o^* a Enoyl CoAhydratase

OH

P - hydroxyacylCoA

o n — o n 0

A2- Enoyl CoAk2 - - _ "2° OH

Phan tfng oxy hoa ldn 2

Dtfdi stf xiic tac ciia enzym P-hydroxyacyl CoA dehydrogenase, cd coenzym la NAD

chtfc alcol bac 2 dtfdc oxy hda thanh chtfc ceton:

P -hydroxyacyl CoA dehydrogenase '

Phan tfng phan cat din xuat fi-cetonic (stf thio gidi)

Nhdm thiol ciia CoA tac dong tai Cp ciia P-ceto acylCoA, phan cSt lien ke't gitfa Ca va Cp, tach mot phan tu* acetyl CoA ra khoi p- cetoacyl CoA Phan tfng nay dtfdc xiic tac bdi enzym P-

cetothiolase (acyl CoA acetyl transferase) va cd stf tham gia ciia mot phan tir coenzym Attf do:

Acyl-CoA acetyl transferase

Acyl CoA Acetyl CoA

P - cetoacyl CoA

Nhtf vay, ket qua ciia mot chu trinh p oxy hda la tach ra dtfdc mot phan tuf acetyl CoA va

mot phan ttf acyl CoA ngan di 2 C so vdi acid beo ban dau

Acyl CoA ngan di 2 C lai tie'p tuc bi [O] qua cac giai doan nhtf tren cho den khi toan bo

phan ttf acid beo bien thanh acetyl CoA

Phtfdng trinh tong quat ciia stf p oxy hda acid beo cd dang:

C H O + (n-1) CoASH + (n-1) FAD + (n-1) NAD+ + (n-1) H20

^ n Acetyl CoA + (n-1) FADH2 + (n-1) NADH + (n-1) H+

(n=m/2)

Vi du: neu acid beo la acid palmitic cd 16C, dtfdc hoat hda thanh palmityl CoA sau 7

vong oxy hda se tao thanh 8phan m* acetyl CoA theo phtfdng trinh phan tfng sau:

^ 8 Acetyl CoA + 7 FADH2 + 7 NADH + 7H+

Mg2+

• AMP + PP

Palmityl CoA (16C)

H20 2H _* FAD 2H _v NAD

Hinh 2.3 Sd do ciia qua trinh P - oxy hda acid palmitic.

2.2.1.3 Stf td'ng ke't nang Itfr/ng cua qua trinh thoai hda acid beo.

-♦ Hai phan tfhg p- oxy hda phdng thich 4H, trong do 2Hdtfdc chuyen chd bdi FAD

(FADH2) va 2H dtfdc chuyen chd bdi NAD (NADH + H+).

Trong chudi ho hap te' bao, stf oxy hda tie'p 1phan ttf NADH +H+ giai phon* 3ATP 1phan ttf

FADH2 giai phdng 2ATP

Nhtf vay moi^vdng Poxy hda cung cap 5ATP va tach ra mot phan tii* acetyl CoA.

♦ M6i phan tii acetyl CoA tie'p tuc bi oxy hda trong chu trinh Krebs va giai phdng

Mot phan tu" acid beo cd so' Cchan (2n), sau khi [O] de'n cung se cho:

n phan ttf acetyl CoA hay 12n phan ttf ATP

(n -1) phan ttf FADH2 va NADHH+ hay 5(n-l) ATP

♦ Nhtf vay, nang Itfdng to'ng cong thu dtfdc la [5(n -1) + 12 n] ATP

Neu trtf 2 ATP da dung trong qua trinh hoat hda acid beo, thi ltfdng ATP thu dtfdc se

Vi du: Stf [O] 1phan ttf acid stearic cd 18 C(n =9) se cung cap (17x 9) -7 ="l46 ATP

2.2.1.4 Cac con dtfoTng thoai hda ti§p tuc cua acetyl CoA

Oxy hoa d chu trinh Krebs

Sau qua trinh p oxy hda, acid beo bien thanh cac phan t& acetyl CoA.

Acetyl CoA se vao chu trinh Krebs, tiep tuc bi [O] hoan toan thanh C02 va H20.

Stf tao thanh cac the ceton

Acetyl CoA dtfdc tao thanh ttf phan tfng p oxy hda ciia acid beo cung cd the' bien &8\ thanh cac

the ceton Cac the ceton gom cd: acetoacetat, p - hydroxybutyrat va aceton.

CH3 - C - CH3

II 0

Qua trinh tao thanh the ceton qua cac giai doan sau:

- Hai phan tu* acetyl CoA ngtfng tu vdi nhau tao thanh aceto acetyl CoA, dtfdi tac dong

ciia enzym P-cetothiolase

- Aceto acetyl CoA ngtfng tu vdi 1 phan tii acetyl CoA nffa tao thanh metylglutaryl CoA (HMG CoA) dtfdi tac dong cua enzym HMG CoA synthetase Sau do, chat

P-hydroxy-p-nay phan tich de cho trd lai acetyl CoA va acetoacetat dtfdi tac dong cua enzym HMG CoAlyase.-

- Acetoacetat bi khuf thuan nghich de tao thanh p-hydroxybutyrat dtfdi tac dong ciia

enzym p-hydroxybutyrat dehydrogenase Acetoacetat bi khu' nhdm carboxyl dtfdi tac dong ciia

enzym acetoacetat decarboxylase de tao thanh aceton

Hinh 2.4 Sd do stf tao thanh the ceton ttf acetyl CoA

Acetoacetat, P -hydroxybutyrat dtfdc tao thanh d gan, vao mau roi chuyen de'n cac to

chtfc Tai day, chung dtfdc bie'n do'i thanh acetyl CoA va bi oxy hda trong chu trinh acid citric de

cung cap nang tong cho mo, dac biet la cd xtfdng, cd tim va vo thtfdng than Nao thtfdng stf

dung.nangltfdng ttf glucose, cb thi thay bang nang ltfdng tilr cac cha't tren khi bi doi keo dai hay

Binh thtfdng, n6ng do aceton dtfdc tao thanh ttf acetoacetat ra't thap Khi ddi glucid hav

khi bi benh tieu dtfdng khong dieu tri, ndng do cha't nay trong mau tang, do stf gia tang nhip d6

oxy hoa cac acid beo dtf trtf tao ra nhieu acetoacetat Aceton dtfdc bai xua't qua khi thd ra va

ntfdc tieu Trtfdng hdp nang cd the dan de'n nhiem acid huyet va hon me.

Do do, stf tao thanh cac the' ceton benh ly la hau qua cua stf ma't can do'i gitfa hai qua

trinh chuyen hda glucid va lipid; hay noi each khac, do td'c do tao thanh cac cha't nay tron* gan

vtfdt qua kha nang sir dung chiing trong cac mo ngoai vi &

Cac con during chuyen hoa khac

Acetyl CoA cung cd the' dtfdc cd the' stf dung lam nguyen lieu de' to'ng hdp cholesterol

hoac tai tao acid beo.

2.3 Su* oxy hda acid beo bao hoa cd so'C le

Qua trinh oxy hda ctfng thtfc hien gidng nhtf tren, nhtfng san pha'm cuo'i cung cua stf

B-oxy hoa la propionyl CoA (thay vi acetyl CoA).

Propionyl CoA dtfdc tie'p tuc thoai hda b^ng phan tfng carboxyl hda chuye'n thanh methyl

malonyl CoA, vdi stf xiic tac cua enzym pcopionyl-CoA carboxylase, coenzym la biotin va ATP

(chat cung cap nang Itfdng); sau do chuye'n thanh succinyl CoA nhd stf xiic tac ciia methyl

malonyl CoA mutase cd coenzym la vitamin Bi2 :

Propionyl CoA carboxylase

Propionyl CoA C02 Biotin, ATP Chi

Methyl malonyl CoA

Coenzym B12 Meiyl malonyl CoA

mutase

HOOC_CH2_CH2-CO~SCoA

Succinyl CoA

/Krebs)

Hinh 2.5 Stf thoai hda tiep tuc ciia propionyl CoA.

2.4 Suf oxy hda acid beo chtfa bao hoa

Cac acid beo chtfa bao hda dtfdc oxy hda gan gidng nhtf acid beo bao hda nhtfng can bo'

sung mot so enzym.

- Trong qua trinh oxy hda, sau khi phan cat dan nhtfng mlu 2C ke ttf dau cd nhdm

carboxyl, acid beo chtfa bao hoa cd lien ket doi dang cis se tao ra cac acyl CoA chtfa bao hda

(enoyl CoA) cd lien ke't doi gitfa C3 va C4 (A3), chtf khong phai la lien ke't doi gitfa C2 va C3

(A ) gidng nhtf trong phan ttf cac chat chuyen hda trung gian ciia acid beo bao hoa.

Do do, trong qua trinh oxy hda, can cd them hai enzym phu la enoylCoA isomerase va 2,4

-dienoyl - CoA reductase.

- Vi enzym enoyl- CoA hydratase chi tac dong tren hdp chat dang trans, nen can cd them

enzyirfenoyl - CoA isomerase de bie'n ddi lien ke't doi ttf dang cis sang dang trans va chuyen ttf

vi tri A3 sang A"

Vi du: Trong stf thoai hda ciia acid oleic, oleoyl CoA trai qua ba vdng oxy hda tach ra

dtfdc 3 phan ttf acetyl CoA va mot phan ttf cis - A3 -dodecenoyl- CoA khong the chuyen hda tiep

dtfdi tac dong ciia enzym enoyl CoA hydratase

Dtfdi tac dong ciia enzym A3, A2 - enoyl- CoA isomerase, cis -A3- enoyl CoA dtfdc dong

phan hda thanh trans -A2 - enoyl CoA ; cha't nay chiu tac dung ciia enzym enoyl- CoA hydratase tao thanh P- hydroxy dodecenoyl- CoA (trans - A2 dodecenoyl - CoA).

Sau do, qua trinh oxy hda tie'p tuc gio'ng nhtf cac giai doan cua stf oxy hda acid beo baohda.

- Do'i vdi cac acid beo chtfa bao hda co nhieu lien ke't doi, nhtf acid linoleic 18:2 (A ' *),

can cd them mot enzym thtf hai de hoan thanh stf oxy hda, do la 2,4 - dienoyl CoA reductase

Vi du: Linoleoyl-CoA qua 3 vdng p oxy hda tach ra dtfdc 3 phan ttf acetyl CoA, phan

acylCoA con lai cd 12C vdi hai lien ke't doi dang cis la cis -A3 va cis - A6.

Dtfdi tac dung ciia enoyl- CoA isomerase, hdp chat nay dtfdc bie'n do'i thanh dong phantrans -A , cis - A

- Qua trinh ^oxy hda tie'p tuc de tao thanh trans A2, cis A4-dienoyl CoA va enzym 2,4

dienoyl CoA reductase se xiic tac phan tfng chuyen hdp chat nay thanh cis -A - enoyl CoA

Sau do, cd chat nay dtfdc enzym enoyl CoA isomerase bie'n ddi thanh trans - A2 enoyl CoA va

qua trinh oxy hda lai tie'p tuc nhtf binh thtfdng

- So' ltfdng ATP dtfdc tao thanh trong qua trinh oxy hda acid beo chtfa bao hoa it hdn sovdi qua trinh oxy hda acid beo bao hda cd cung so'C