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Introduction
Vitamins are an organic chemical
compound
which
the
body
requires in small amounts for the
metabolism and to protect your
health.
Vitamins assist the body in
functioning properly by helping
in the formation of hormones,
blood cells, nervous-system
chemicals and genetic growth.
An over dose can be harmful to
your health.
The Body & Vitamins
The body can only produce one
vitamin naturally by itself.
This is vitamin D. All other
vitamins that the body
requires to function properly
have to be derived from the
diet. Lack of vitamins can
have a serious affect on your
health and may end in
metabolic
and
other
dysfunctions.
Vitamin Groups
Vitamins are divided up into two
main groups which are fatsoluble vitamins and watersoluble vitamins. Fat-soluble
vitamins are usually found in
foods that contain fat.
The body stores the fat
soluble
vitamins
and
because of this, people don’t
usually need to make a
special effort to include
them in their diet.
Vitamin Groups
Water soluble vitamins
can’t be stored in the
body for a long time and
have to be replenished
everyday.
In some cases when it’s
not possible to obtain
these vitamins in a
regular diet, they have
to be acquired by other
vitamin supplements.
Water-Soluble Vitamins
• Water soluble
• Readily excreted – expensive urine
• Can be lost from food by
cooking/storage
• Typically work as part of enzymes in
metabolism
• Relatively high absorption rate
• Severe deficiencies rare
Thirteen complete Vitamins
Water soluble Vitamins
Fat-Soluble Vitamins












Vitamin B1 (Thiamin)
Vitamin B2 (Riboflavin)
Vitamin B6 (pyridoxine)
Vitamin B12
(Cyanocobalamin)
Vitamin Biotin (Vitamin H)
Vitamin C (Ascorbic Acid)
Vitamin P (Bioflavonoids)
Niacin (Niacinamide)
Vitamin A & Beta carotene
Vitamin D
Vitamin E
Vitamin F (unsaturated fatty
acids)
 Vitamin K (Menadione)
Vitamin K cycle
GLU
residue
R
NH
CH
O2 + CO2
CH2
CH2
R
+
H2O +H
CO2 -
NH
CH CH2
carboxylase
C= O
GLA
residue
CH
CO2CO2-
C= O
R
R
K(red)
K(epox)
vitamin K
reductase
epoxide
reductase
K(ox)
D
i
e
t
coumarins

Ca

Thrombin Activation
vWF
WOUND
collagen
endothelium

Thrombin
Pro-Thrombin
platelet
Va
Xa


 
Ca

 


Ca

 
Gla
Gla
Gla Gla
S
S
S
S
proteolytic cut
PL surface
ProNH2
NH2
COOH
COOH
C
i
r
c
u
l
a
t
i
o
n
The common pathway
*Xa
Va
prothrombin
Common
pathway
V
fibrinogen
*thrombin
XIII
CLOT
XIIIa
Fibrin monomer
Fibrin polymer
O
O
H3C
CH2
N
H3C
CH2
H
O
P
O
O
+
N
C
N
CH2
P
O
S
acidic H+
NH2
thiamine pyrophosphate (TPP)
Thiamine pyrophosphate (TPP) is a derivative of
thiamine (vitamin B1).
Nutritional deficiency of thiamine leads to the
disease beriberi.
It affects especially the brain, because TPP is
required for CHO metabolism, and the brain
depends on glucose metabolism for energy.
O
dimethylisoalloxazine
O
H
C
C
N
O

H3C
C
C
C
NH
H3C
C
C
C
C
C
H
N
H
C
+
2e +2H
O
N
H
N
H3C
C
C
C
NH
H3C
C
C
C
C
C
H
CH2
FAD
N
O
N
H
CH2
HC
OH
HC
OH
HC
OH O
H2C
C
O
P
O-
Adenine
O
O
P
O-
O
Ribose
FADH2
HC
OH
HC
OH
HC
OH O
H2C
O
P
O-
Adenine
O
O
P
O
Ribose
O-
FAD (Flavin Adenine Dinucleotide is derived from
the vitamin riboflavin. The dimethylisoalloxazine ring
system undergoes oxidation/reduction.
FAD is a prosthetic group, permanently part of E3.
Reaction: FAD + 2 e- + 2 H+  FADH2
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Glossitis (Fig. 10-4)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Dermatitis of Pellegra (Fig. 10-5)
S
CH2
CH2
S
lipoic acid
CH
O
CH2 CH2 CH2 CH2 C
Lipoamide
includes a
dithiol that
undergoes
oxidation/
reduction.
lipoamide
lysine
NH
NH (CH2)4 CH
C
O
2e + 2H+
HS
CH2
CH2
HS
O
CH
CH2 CH2 CH2 CH2 C
dihydrolipoamide
NH
NH (CH2)4 CH
C
O
S
CH2
CH2
S
CH
lipoic acid
O
CH2 CH2 CH2 CH2 C
lipoamide
lysine
NH
NH (CH2)4 CH
C
O
2e + 2H+
The carboxyl at the end of lipoic acid's
HS CH2 chain forms an amide bond to the ehydrocarbon
amino groupCH
of2 a lysine residue of E2, yielding
NH
O
HS
CH
lipoamide.
CH2 CH2 CH2 CH2 C
NH (CH2)4 CH
A long flexible arm, including hydrocarbon chains
C Odithiol
of lipoate and the lysine R-group, links each
of lipoamide to one of two lipoate-binding domains
of E .
O
C CH3
Coenzyme A-SH + HO
acetic acid
O
Coenzyme A-S
C
CH3 + H2O
acetyl-CoA
In the overall reaction
catalyzed by the
Pyruvate
Dehydrogenase
complex, the acetic
acid generated is
transferred to
coenzyme
A.
H
O
O
H
H
C
The final electron
acceptor
is NAD+.
C
NH2
+
N

NH2
+
2e + H
N
R
R
NAD+
NADH
Sequence of reactions catalyzed by Pyruvate
Dehydrogenase complex:
1. The keto C of pyruvate reacts with the carbanion
of TPP on E1 to yield an addition compound.
The electron-pulling (+) charged N of the thiazole
ring promotes CO2 loss. Hydroxyethyl-TPP
remains.
2. The hydroxyethyl carbanion on TPP of E1 reacts
with the disulfide of lipoamide on E2. What was
the keto C of pyruvate is oxidized to a carboxylic
acid, as the lipoamide disulfide is reduced to a
dithiol.
The acetate formed by oxidation of the
hydroxyethyl is linked to one of the thiols of the
Sequence of reactions (continued)
3. Acetate is transferred from the thiol of
lipoamide to the thiol of coenzyme A, yielding
acetyl CoA.
4. The reduced lipoamide, swings over to the E3
active site.
Dihydrolipoamide is reoxidized to the
disulfide, as 2 e- + 2 H+ are transferred to a
disulfide on E3 (disulfide interchange).
5. The dithiol on E3 is reoxidized as 2 e- + 2 H+
are transferred to FAD.
The resulting FADH2 is reoxidized by electron
transfer to NAD+, to yield NADH + H+.
View an animation of the Pyruvate Dehydrogenase
reaction sequence.
O
H3C
C
S
CoA
acetyl-coenzyme A
Acetyl CoA, a product of the Pyruvate
Dehydrogenase reaction, is a central compound in
metabolism.
The "high energy" thioester linkage makes it an
excellent donor of the acetate moiety.
glucose-6-P
Glycolysis
pyruvate
fatty acids
acetyl CoA
oxaloacetate
ketone bodies
cholesterol
citrate
Krebs Cycle
Acetyl CoA functions as:
 input to Krebs Cycle, where the acetate moiety
is further degraded to CO2.
 donor of acetate for synthesis of fatty acids,
ketone bodies, & cholesterol.
Biosynthesis of Amino Acids:
Transaminations
Amino Acid1 +a-Keto Acid2
NH3 +
-
O 2 CCH 2 CH 2 CHCO 2 -
Glutamate
O
O 2 CCH 2 CH2 CCO 2 -
a-Ketoglutarate
Amino Acid2 +a-Keto Acid1
O
R-CCO 2 -
+
Pyridoxal phosphate (PLP)Dependent Aminotransferase
+
NH2
R-CHCO 2 -
Transaminations: Role of PLP
CO2 H
CHO
CH2 OPO3-2
HO
H3 C
CH2 OPO3-2
HO
N
H3 C
+
H
-
C
NH3
+
N CHCH2 CH2 CO2-
N
+
H2 O
H
O 2 CCH 2 CH 2 CHCO 2 -
Tautomerization
CO2 -
O
-
O 2 CCH 2 CH 2 CCO 2 -
N CCH2 CH2 CO2-
CH2 NH2
HO
H3 C
CH2
CH2 OPO3-2
N
+
H
CH2 OPO3-2
HO
H2 O
H3 C
N
+
H
Vitamin-Coenzymes in Amino
Acid Metabolism
• Vitamin B-6 : pyridoxal
phosphate
– Enzymes that bind amino
acids use PLP as
coenzyme for binding
• Transaminases
• Amino acid
decarboxylases
• Amino acid deaminases
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Absorption of Vitamin B-12 (Fig. 10-10)
Vitamin-Coenzymes in Amino
Acid Metabolism
• Vitamin B-12
– Catabolism of BCAA
• Methyl-malonyl CoA
mutase (25-9 &10)
Vitamin-Coenzymes in Amino
Acid Metabolism
• Vitamin B-12
– Methionine
synthesis/recycling
• Methionine as a
methyl donor
– Choline and creatine
synthesis
– Homocysteine is
product
– HCys -> Met
requires B-12
Vitamin-Coenzymes in Amino
Acid Metabolism
• Folacin:
Tetrahydrofolate
(THF)
– Carrier of single
carbons
•
•
•
•
•
Donor & receptor
Glycine and serine
Tryptophan degradation
Histidine degradation
Purine and pyrimidine
synthesis
Ascorbic Acid Structure
OH
O
HO
HO
O
OH
(AscH2)
AscH2 is a Di-acid
OH
O
HO
OH
O pK = 4.1
1
OH
HO
AscH2
O
HO
O
OH
O
OH
AscH
O
pK2 = 11.8 HO
O
O
2-
O
Asc
At pH 7.4, 99.95% of vitamin C will be present
as AscH ; 0.05% as AscH2 and 0.004% as Asc2. Thus, the antioxidant chemistry of vitamin C is
the chemistry of AscH .
OH
O
HO
HO
O
+H
+
+
-H pK = 4.1
OH
OH
O
HO
O
O
AscH-
+H+
-e
O
HO
OH
O
-H+ pK = 11.8
+H
Asc2
+
OH
-H
+
pK = -0.86
OH
O
O
O
AscH
OH
HO
Forms of
Ascorbate
OH
AscH2
O
-e
O
HO
O
OH
O
Asc
O
-e
O
O
O
O
O DHA O
-H2O +H2O
OH
HO
HO
HO
O
+H2O
HO
OH
HO OH
DHAA (2)
-H2O
O
O
O
OH
HO OH
DHAA (1) (>99%)
(pK ~ 8-9)
OH
HO
OH
O
-e -2H+
O
OH
O
HO
O
-e
+
+e +2H
HO AscH OH
HO
O
O
C
O
O
+H2O
Asc
O
O
C
H C OH
C O
H C OH
HO C H
CH2OH
CH2OH
L-xylonic
acid
2,3-diketo-Lgulonic acid
CH2OH
O
O
H C OH
+
C
O
OH
C
OH
C
HO C
CH2OH
L-xylose
OH
C O
HO C H
C O
O
O DHA O
OH
H C OH
O DHA O
O
+e
2
OH
HO
H C OH
HO C
OH
oxalic acid
CH2OH
L-threonic
acid
O
C
OH
HO C H
+
H C OH
HO C H
CH2OH
L-lyxonic acid
Ascorbate
Falling
Apart
-
AscH is a Donor Antioxidant
OH
O
HO
OH
+
OH
O
AscH
O
HO
O
O
R
+ RH
O
O
Asc
AscH- donates a hydrogen atom (H or H+ + e-) to an
oxidizing radical to produce the resonance-stabilized
tricarbonyl ascorbate free radical. AscH has a pKa of
-0.86; thus, it is not protonated in biology and will be
present as Asc-.
Ascorbate, Summary
Ascorbate is a versatile, water soluble, donor,
antioxidant.
Thermodynamically, it can be considered to be the
terminal, small-molecule antioxidant.
OH
O
HO
OH
+
OH
O
AscH
O
HO
O
O
R
+ RH
O
O
Asc