Vitamin B12 Cobalamin

1
Vitamin B12 ( Cobalamin )

• ?????????? corrin ring ( complex tetrapyrrol
• ring structure ) ??? cobalt ion ???????????
• coenzyme form ????????? coenzyme B12 ????
• 5/-deoxyadenosylcobalamin ?? R group ????
• 5/-deoxyadenosyl group

2
????? Murray et al, 1996
3
Coenzyme B12
????? Nelson and Cox, 2000
4

• vitamin B12 ??????????????? microorganisms ,
  ???? liver
• ????? methylcobalamin ???? 5/ -
  deoxyadenosylcobalamin
• ????????? protein
• vitamin B12 bound protein
• pernicious anemia ????????????????????
  vitamin B12 ?????
• red blood cells ????????????????????????????
  ??

gastric acids ( stomach ) trypsin ( small
intestine )
hydrolysis of protein
active vitamin B12
5
Ileum ( small intestine )
blood circulation
receptor site
cobalamin - intrinsic factor complex
cobalamin
cobalamin
intrinsic factor
intrinsic factor ( glycoprotein )
transcobalamin II
parietal cells ??? gastric mucosa ( stomach )
tissues
6
Metabolism ??? Propionate
????? Murray et al, 1996
7
???????????????????????????? vitaminB12
coenzyme-dependent enzymes
????? Murray et al, 1996
8
PANTOTHENIC ACID ( VITAMIN B5 )

• ??????????????????? b - alanine ??? pantoic
  acid
• ????????????????????????? coenzyme A( CoASH ,
  CoA ), acyl carrier protein ( ACP )?? fatty
  acid synthase complex
• ????????????? acyl group carrier

9
Pantoic acid
b-alanine
Pantothenic acid
Coenzyme A( CoASH , CoA )
????? http//www.indstate.edu/thcme/mwking/vitam
ins.html
10
b-Mercaptoethylamine residue
Pantothenic acid residue
????? Voet and Voet, 1995
11
VITAMIN C ( ASCORBIC ACID )
Ascorbic acid Ascorbate Dehydroascorbic aci
d
pKa 4.2
O-
????? http//www.indstate.edu/thcme/mwking/vitam
ins.html
12
O
O
C
C
OXIDATION
C
HO
C
O
O
O
C
HO
C
O
HC
HC
HOCH
HOCH
REDUCTION
CH2OH
CH2OH
GSSG
2 GSH
L - Ascorbic acid
Dehydroascorbic acid
( biological active ?????? stable )
GSH glutathione ( reduced form ) 1
molecule GSSG glutathione ( oxidized form )
2 molecules
13
BIOSYNTHESIS ??? VITAMIN C
Glucose
D - Glucuronate
L - Gulonate
L - Gulonolactone
L - gulonolactone oxidase (??????? primates )
3 - Keto - L - gulonolactone
L - Ascorbic acid
14
?????????? VITAMIN C
???? reducing agent ??????????????????? ????
Posttranslational modification ??? collagens
hydroxylation
Proline
Hydroxyproline
prolylhydroxylase ( vitamin C ???? cofactor )
vitamin C ????????????? reducing agent
???????????? Fe2 ????????? active site ???
enzyme prolylhydroxylase
15
GLUTATHIONE TRIPEPTIDE
glu - cys - gly NADPH H
2 glu - cys - gly NADP
s
SH
s
reduced glutathione ( GSH )
glu - cys - gly
oxidized glutathione ( GSSG )
????? Murray et al, 1996