HO
a
0
Tocopherol
A,
R,
HO
eee
R,
Tocotrienol
FIGURE
44-5
vitamin
€
vitamers.
In
a-tocopherol
and
tocotrienol
R,, R,,
and
R,
are
all
—CH,
groups.
In
the
B-vitamers
R,
is
H,
in
the
y-vitamers
R,
is
H,
and
in
the
6-vitamers
R,
and
R,
are
both
H.
Free
caches!
“
PuFA—
00-
PuFA—O00H
a
TooOH
acd:
od
il
PuFA—H
Membrmes
eee
Oyo
Vearw
A=
ag
eC
PUFA
COM,
_
i
a
Ko,
a
Supercmde
PUFA—OH
Week 6 Vitamins and Minerals
du,
Iw—i—C-=0
Carboxygiutamate
residue
enzyme
b=
CH;—
COO
0,
*cH—Coo"
be
dn,
Phylloquinone
OH
Qo
o
CH,
H
R
-
.
cH,
OH
oO
—o
Vitamin
K
hydroquinone
‘Vitarnin
K
epoxide
on
I
Dieters,
ou
cH,
ou
NADIA
CH,
Crmiticns
Monadiol
cal
R
oO
(acotomenaphthona)
Vitarnan
K
quinone
menadione)
and
menadiol
diacetate
are
synthetic
FIGURE
44-7
The
vitamin
K
vitamers.
Menadiol
(or
,,
FIGURE
44-8
Therole
of
vitamin
in
the
synthesis
of
that
are
converted
to
menaquinone
in
the
liver.
y-carboxyglutamate.
_
HO-CH,
~
node
~~
HO—
ve
<4
ie
FIGURE
44-19
vitamin
c.
Week 6 Vitamins and Minerals
Ascorbic
acid
(Vitamin
C)
Useful
as an
antioxidant,
hepatic
synthesis
of
bile
acids,
intestinal
absorption
of
iron
and
as
a
co-factor
for
proline/lysine
hydroxylases
(posttranslational
modification
of
procollagen
to
collagen),
osteocalcin
and
C1
complement
protein
synthesis,
Aspartate
hydroxylase
(posttranslational
modification
of
protein
C
—
which
inactivates
Factor
V
in
the
clotting
cascade,
trimethylysine
hydroxylase
(carnitine
synthesis).
It
is
also
required
for
dopamine
B-hydroxylase
activity
(catecholamine
synthesis
from
tyrosine)
Deficiency
results
from
overheating
baby
formulas
or
milk
(it
is
heat-labile),
diets
deficient
in
citrus
or
green
vegetables.
TIRER
Vitamin
K
and
Vitamin
C
How
can
you
distinguish
Vit
K
deficiency
from
Vit
C
deficiency?
Easy
bruising
and
bleeding
Easy
bruising
and
bleeding
Normal
bleeding
time
Increased
bleeding
time
Increased
Prothrombin
time
Normal
Prothrombin
time
Hemorrhagic
disease
with
no
connective
Gum
hyperplasia,
inflammation,
loss
of
tissue
problems
teeth,
skeletal
deformity
in
children,
poor
wound
healing,
painful
glossitis,
anemia
Caused
by
fat
malabsorption,
long-term
Caused
by
diets
deficient
in
citrus
fruits
antibiotic
therapy,
newborns
and
green
vegetables
Week 6 Vitamins and Minerals
Kg
Loi
yor
oro
fic
thot
oto
CHM
5
§
¥
FIGURE
44-9
Thiamin,
thiamin
v
Thamn
Thamn
diphosphate
Carbanon
Thiamine
(B1)
A
co-factor
for
PDH,
transketolase
(PPP)
and
a-
ketogluterate
dehydrogenase
(TCA
cycle)
Thiamine
triphosphate
activates
chloride
channels
in
neurons
—
nerve
conduction
Caused
by
alcoholism
Deficiency
—
Chronic
peripheral
neuritis,
Beri-beri
(with
or
without
heart
failure),
Wernicke
(ataxia,
nystagmus,
opthalmoplegia),
Korsakoff's
syndrome
(confabulation
and
psychosis)
Erythrocyte
transketolase
assay
is
used
to
evaluate
nutritional
status
Riboflavin
(B2)
FMN,
FAD(H2)
Dietary
sources
—
Milk
and
diary.
Has
a
yellow
color
and
can
be
used
as
food
coloring
Co-factor
for
succinate
dehydrogenase
(TCA
cycle,
ETC,
amino
acid
oxidation),
M(L)CAD
(fatty
acid
oxidation)
Deficiency
—
Corneal
neovascularization,
cheilosis/stomatitis
(scaling
of
lips
and
cracking
of
mouth),
Magenta
colored
tongue
Erythrocyte
glutathione
reductase
assay
(which
is
FAD
dependent)
is
used
to
evaluate
nutritional
status
Week 6 Vitamins and Minerals
or
on
Niacin
(nicotinic
acid
and
nicotinamide)
See
also
Figure
7-2
FIGURE
44-11
Niacin
(nicotinic
acid
and
nicotinamide).
Niacin
(B3)
Useful
for
NAD+,
NADH,
anti-hyperlipidemic
agent,
providing
ADP-
ribosylation
of
proteins
for
gene
regulation,
apoptosis
and
signaling
Synthesized
from
tryptophan
de novo
but
can
be
inhibited
by
excess
leucine
as
in
HMG-CoA
lyase
deficiency
due
to
the
inhibition
of
quinolinate
phosphoribosyl
transferase
Other
causes
include
Hartnup
disease
(defective
membrane
transport
of
tryptophan
in
the
intestines
and
kidneys)
and
carcinoid
syndrome
(increased
synthesis
of
5-hydroxytrptamine
-
serotonin)
Deficiency
—
Pellagra
(Photosensitive
dermatitis,
dementia
and
diarrhea)
Common
in
areas
where
corn
is
the
staple
food
because
tryptophan
is
not
free
in
corn
(but
soaking
in
lime
—
nixtamalization,
releases
the
tryptophan)
Excess
of
niacin
can
cause
skin
irritation,
vasodilation
(flushing)
and
liver
damage
Pyridoxine
(BG)
Useful
co-factor
for
ALT,
AST,
ALA
synthase
(heme
synthesis),
glycogen
phosphorylase,
cystathionine
synthase
and
lyase
(homocysteine
metabolism),
removal
of
hormone-receptor
complex
from
DNA-binding
to
terminate
the
action of
steroid
hormones.
Deficiency
is
caused
by
Isonaizid
therapy
and
results
in
sideroblastic
anemia,
stomatitis
and
convulsions.
Also
implicated
in
hormone
sensitive
cancers
(e.g.
breast
and
prostate).
An
excess
of
pyridoxine
causes
sensory neuropathy
Nutritional
status
can
be
evaluated
by
measuring
throcyte
transaminase
activit
FIGURE
44-12
interconversion
of
the
vitamin
B, vitamers.
Week 6 Vitamins and Minerals
FIGURE
44-13
vitamin
B,..
Four
coordination
sites
on
the
central
cobalt
atom
are
chelated
‘by
the
nitrogen
atoms
of
the
corrin
ring,
and
one
by
the
nitrogen
of
the dimethylbenzimidazole
nucleotide.
The
sixth
coordination
site
may
be
occupied
by: CN’
(cyanocobalamin),
OH-
(hydroxocobalamin),
H,O
(aquocobalamin,
—CH,
(methyl
cobalamin),
or
5°
(adenosylcobalamin).
Cobalamin
(B12)
Cobalt-containing
compounds
derived
from
animal
foods.
It
is
bound
to
cobalophilin
(secreted
by
the
saliva),
then
released
in
the
duodenum
to
bind
intrinsic
factor
(produced by
gastric
parietal
cells).
The
Vit
B12-
intrinsic
factor
complex
is
then
absorbed
in
the
ileum.
It
is
a
co-factor
for
methionine
synthase,
homocysteine
methyltransferase,
methylmalonyl-CoA
mutase
and
leucine
aminomutase
Vit
B12
deficiency
causes
folate
trapping
(functional
folate
deficiency)
as
Methyl-THF
due
to
the
impaired
Yeu
IN
me)
man
edtaelainemsy
alae
rte
Pancre
ss
He-s
(CHa),
—
H—C—NHY
H—-C—NM,’
coo-
coo-
[sme]
(Mettii—H,tolatio
Be
H,
folate
FIGURE
44-14
Homocysteine
and
the
“folate
trap.”
Vitamin
B,,
deficiency
leads
to
impairment
of
methionine
synthase,
resulting
in
accumulation
of
homocysteine
and
trapping
folate
as
methyltetrahydrofolate.
Week 6 Vitamins and Minerals
Folic
Acid
Pteroyl
glutamate.
Folinic
acid
—
5-formyl
THF
(stable,
also
Leucovorin
(racemic
mixture)
Useful
for
thymidylate
synthase
—
DNA
synthesis,
purine
synthesis
Alcoholism
and
pregnancy
deplete
stores
He—O
Hc=0
Hany
SFommITHE
41
Ay
i
10-Formy!
THF
Ho—NH
HNN
i
5-Formimino
THF
LY
canoe
CH,
Shes.
OE
—i—
N
—N—
HNN
i
SMatyTHE
yy
4
5.10-Methonyt
THF
FIGURE
44-15
Tetrahydrofolic
acid
and
the
one-carbon
substituted
folates.
Week 6 Vitamins and Minerals
Sources
of one-carbon
units
Synthess
using
one-carbon
unsts
Senne
Seine
Gyone-qaan
Methylene-THF
——»
Methy-THF
—+
Mothionne
Choline
|
TMP
-
ditiydrotoiate
™a
+4S20N
—»
Formimino-THF
——»
Methemy!.THF
DNA
FIGURE
44-16
Sources
and
utilization
of
one-carbon
substituted
folates.
‘co,
Homocysteinemia/Homocysteinuria
Genetic
homocysteinemia
is
rare
but
results
from
deficiency
of
cystathionine
synthase
deficiency
or
methyltetrahydrofolate-
homocysteine
methyltransferase
deficiency.
There
is
accumulation
of
homocysteine
and
methionine
in
the
blood.
They
are
at
risk
of
developing
cardiovascular
diseases,
deep
vein
thrombosis,
stroke,
dislocation
of
the
lens
and
mental
retardation.
Hamocysteinemia
can
be
from
deficiencies
of
folate,
Vit
B6
and
B12
and
also
presents
with
atherosclerosis,
DVT
and
stroke.
=—=§
One
Carbon
Units
in
Biochemical
Reactions
S-Adenosylmethionine
(SAM);
It
is
synthesized
from
methionine
and
is
involved
in
the
synthesis
of
epinephrine
and
7-methylguanine
cap
on
eukaryotic
MRNA.
It
donates
the
methyl
group
and
is
converted
to
homocysteine.
Tetrahydrofolate
(THF);
Formed
from
folate via
dihydrofolate
reductase
and
is
required
for
purines
and
pyrimidine
synthesis
-
DNA/RNA
during
cell
division
and
growth.
Methotrexate
is
a
dihydrofolate
reductase
inhibitor
and
it
is
used
as
an
anticancer
drug
and
in
rheumatoid
arthritis.
Cobalamin
(Vit
B12)
LIBERTY
Week 6 Vitamins and Minerals
Vitamin
B12
d
Progre
e
peripheral
neuropathy
Homo
cardi
Methylmalonic
malnutritic
May
be
due
to
pernici
TAME
Haat
tay
See
lel
Erte
el
Hypersegmented
neutrophils,
Large
arbi
mi
meals
TaN
ELI
Threonine
eels
Benes
|
|
la
Tyrosine
esl
Leucine,
Isoleucine,
Valine
:
eee
2
ai)
celery
Homogentisic
acid
Propionyl
CoA
-——
ans
cg
a
Maleyacetoacetate
Methylmalonyl-CoA
180
eee
ur?
|
Senos
eased
Ulan
teleslted
Succinyl-CoA.
Xero
ane)
Aula
Ee
Se
Homocysteine
een
S
EEEESUENN
LILI.
a
y'
Wigs
ed
PLUits
rv
fee
Urs
Es
en
ere
Re
erar
tt
Ts
i
Pec
ee
ea
H20:
eave
eclul
telat)
-Adenosylmethionine
Deu
ae
fee
ty
Le
a-ketobutyrate
ae
[era
(lat
Sa
Giitathione
Week 6 Vitamins and Minerals
¢
Fates
of
homocysteine
—
transsulfuration
to
cysteine
or
remethylation
to
methionine
*
Cysteine
is
needed
to
provide
sulfur
for
protein
synthesis
(disulfide
bonds)
and
collagen
structure
—
this
accounts
for
the
musculoskeletal
defects
in
CBS
deficienc
¢
Cysteine
also
produces
glutathione
(antioxidant)
and
taurine
(neuronal
cell
membrane
integrity)
Methylenetetrahydrofolate
reductase
(MTHFR),
Betaine-Homocysteine
methyl
transferase
(BHMT}, Methionine
synthase
reductase
(MTRR)
—
produces
methyl!
cobalamine
which
is
the
active
form
of
Vit
B12
et
Seam
ene
Methionine
7
_
Tetrahydrofolate
ed
'
ee
Meals
Dee
ee
ie
acd
7
SL
exer
MS,
Vit
812,
Zn
Betaine
—
fat
*
5-Methyltetrahydrofolate
t
Homocysteine
Dietary
Folates
ae
Botn
coo-
Biotnytysine
@ocytn)
L
a
NH
|
—
.
m
|
H
iL
5
.
SCH
-
hu
!
FIGURE
44-17
Biotin,
biocytin,
and
carboxy-biocytin.
Week 6 Vitamins and Minerals
Biotin
¢
Useful
for
acetyl-CoA
carboxylase
(FA
biosynthesis),
pyruvate
carboxylase,
propionyl-CoA
carboxylase
(gluconeogenesis),
methylcrotonyl-CoA carboxylase
(leucine
catabolism)
*
Deficiency
is
rare
but
may
be caused
by
eating
large
amounts
of
raw
egg
white
because
of
avidin
which
can
bind
biotin
strongly
and
prevent
its
absorption.
«
Strreptavidin-biotin
interaction
is
exploited
in
molecular
FIGURE
44-18
Pantothenic
acid
and
coenzyme
A.
Asterisk
shows
site
of
acylation
by
fatty
acids.
Pantothenic
Acid
(B5)
Co-enzyme
A
Useful
in
fatty
acid
synthase,
fatty
acyl
CoA
synthase,
pyruvate
dehydrogenase
Deficiency
is
rare
Week 6 Vitamins and Minerals
