All About Vitamin C: History, Sources, and Benefits
V
i
t
a
m
i
n
C
V
i
t
a
m
i
n
C
•
Vitamin C
also known as
ascorbic acid
or
ascorbate
.
•
The human being is one of the few mammals
unable to synthesize vitamin C.
•
Other animals unable to synthesize vitamin C
include primates, fruit bats, guinea pigs, and
some birds.
•
The inability to synthesize vitamin C results from
the lack of
gulonolactone oxidase
, the last
enzyme in the vitamin C synthetic pathway.
H
i
s
t
o
r
y
o
f
V
i
t
a
m
i
n
C
•
Vitamin C
was
isolated in 1928
, and its
structure was determined in 1933.
•
The problems referred to as
scurvy
and
associated with the lack of vitamin C had been
quite prevalent for centuries. Some of the
most notable stories are those of the British
sailors who often died from scurvy on sea.
V
i
t
a
m
i
n
C
s
t
r
u
c
t
u
r
e
V
i
t
a
m
i
n
C
•
Vitamin C
have a number of vitamiers that
have
vitamin C
activity in animals:
•
Ascorbic acid
in biological system (low pH)
•
Oxidized form
deyhroascorbic acid
.
•
Ascorbate
in neutral salutation (pH>5)
•
Ascorbate and ascorbic acid
are both naturally
present in the body, since the forms
interconvert according to pH.
S
o
u
r
c
e
s
•
Fruits, vegetables and organ meats (liver, kidney).
•
The best food sources of vitamin C include
asparagus, papaya, oranges, cantaloupe,
cauliflower, broccoli, green peppers, grapefruit,
grapefruit, lemons, and strawberries.
•
Citrus products are most commonly cited as
significant sources of the vitamin.
•
Supplements supply vitamin C typically as free
ascorbic acid, calcium ascorbate, sodium
ascorbate, and ascorbyl palmitate.
S
e
n
s
i
t
i
v
i
t
y
o
f
v
i
t
a
m
i
n
C
•
Very significant losses
occur as vegetables
wilt, or when they are cut, as a result of the
release of
ascorbate oxidase
from the plant
tissue.
•
Significant losses
of the vitamin also occur in
cooking
, both through
leaching
into the
cooking water and also
atmospheric oxidation
,
which continues when foods are left to stand
before serving
.
D
I
G
E
S
T
I
O
N
,
A
B
S
O
R
P
T
I
O
N
&
T
R
A
N
S
P
O
R
T
•
Vitamin C does not require digestion prior to being
absorbed into intestinal cells.
•
There is active transport of the vitamin at the
intestinal mucosal brush border membrane
. Both
ascorbate
and
dehydroascorbate
are absorbed across
the buccal mucosa by carrier-mediated passive
processes.
•
Intestinal absorption of dehydroascorbate is carrier
mediated, followed by reduction to ascorbate before
transport across the membrane.
D
I
G
E
S
T
I
O
N
,
A
B
S
O
R
P
T
I
O
N
&
T
R
A
N
S
P
O
R
T
•
Prior to absorption, ascorbic may be
oxidized
to
dehydroascorbate
, which may be absorbed
by facilitated diffusion.
•
Although
dehydroascorbic acid
is absorbed in
higher rate than ascorbate,
the amount of
dehydroascorbic acid found in
plasma and
tissues
under normal conditions is low, as cells
rapidly reduce dehyroascorbic acid to
ascorbate.
D
I
G
E
S
T
I
O
N
,
A
B
S
O
R
P
T
I
O
N
&
T
R
A
N
S
P
O
R
T
•
Simple diffusion (may occur in stomach and
small intestine) provides for vitamin C
absorption with ingestion of higher amounts of
the vitamin.
•
Anion channels in some cells may mediate
vitamin C diffusion faster than the transporters.
•
From intestinal cells, ascorbate may diffuses
through anion channels into extracellular fluid
and enters plasma by way of capillaries.
D
I
G
E
S
T
I
O
N
,
A
B
S
O
R
P
T
I
O
N
&
T
R
A
N
S
P
O
R
T
•
Within intestinal cells:
•
Dehydroascorbic acid is rapidly
reduced
back to
ascorbic acid by enzyme dehydroascorbate
reductase.
•
Glutathione (GSH), which is required for the
reduction of dehydroascorbate, is oxidized in
process. Glutathione spares vitamin C and, in
general, improves the antioxidant protection
capacity of blood.
•
Degree of vitamin C absorption decrease with
increased vitamin intake.
D
I
G
E
S
T
I
O
N
,
A
B
S
O
R
P
T
I
O
N
&
T
R
A
N
S
P
O
R
T
•
Some
80–95%
of
dietary ascorbate
is
absorbed
at usual intakes (up to about 100
mg/day).
•
The fractional absorption of larger amounts of
the vitamin is lower, and unabsorbed
ascorbate from very high doses is a substrate
for intestinal bacterial metabolism, causing
gastrointestinal discomfort and diarrhea.
T
h
e
r
e
d
o
x
c
y
c
l
i
n
g
o
f
a
s
c
o
r
b
a
t
e
i
n
c
h
l
o
r
o
p
l
a
s
t
D
I
G
E
S
T
I
O
N
,
A
B
S
O
R
P
T
I
O
N
&
T
R
A
N
S
P
O
R
T
•
Absorption of ascorbate may be
diminished
in the
presence of
high
intracellular
glucose
, which
appears to interfere with ascorbate transporter.
•
Unabsorbed vitamin C may be metabolized by
intestinal flora.
•
Ingesting large amounts of
iron
with vitamin C
may result in
oxidative destruction of vitamin C
in
digestive tract, yielding other products without
vitamin C activity.
D
I
G
E
S
T
I
O
N
,
A
B
S
O
R
P
T
I
O
N
&
T
R
A
N
S
P
O
R
T
In plasma:
•
Ascorbic acid is transported in the plasma
primarily
in free form as an
ascorbate anion
.
•
Normal plasma level of vitamin C 0.4 – 1.7 mg/dL.
In cells:
•
Uptake of ascorbate
into body cells
requires
sodium and a carrier
and into some cells such as
leukocytes,
uptake is also energy
dependent.
•
Tissue concentrations of vitamin C usually exceed
plasma concentrations
.
D
I
G
E
S
T
I
O
N
,
A
B
S
O
R
P
T
I
O
N
&
T
R
A
N
S
P
O
R
T
•
Ascorbate and dehydroascorbate
concentrations are
much
greater
in
some tissues
than others. The highest
in
adrenal and pituitary glands
(~30-50mg/100 g of wet
tissue).
•
Intermediate
in liver, spleen, heart, kidneys, lungs
pancreas and leukocytes.
•
Smaller
amounts in muscles and red blood cells.
•
Maximal vitamin C
pool is estimated at about 1.500mg.
•
Intakes of about 100-200mg vitamin C/d have been
shown to produce plasma concentrations of about
1.0mg/dL and to maximize body pool.
S
u
m
m
a
r
y
o
f
a
b
s
o
r
p
t
i
o
n
•
Absorbed in the intestine by an energy-requiring,
sodium- dependent, carrier- mediated transport
system.
•
After absorption, ascorbic acid is then
transported as a free acid in plasma into the cells,
including leukocytes and red blood cells.
•
In the tissues, Vitamin C serves as an electron
donor for a number of enzymes.
F
u
n
c
t
i
o
n
&
m
e
c
h
a
n
i
s
m
o
f
a
c
t
i
o
n
•
Vitamin C
has
very complex functional roles
in the body as a
cofactor
in around eight reactions:
1.
Collagen synthesis
2.
Carnitine synthesis
3.
Tyrosine synthesis and catabolism
4.
Neurotransmitter synthesis.
5.
Drug and steroid metabolism.
6.
Maintain the iron and copper atoms in the metalloenzymes
in the reduced state.
7.
In addition vitamin C acting role as reducing agent in
enzymatic reactions.
8.
Ascorbate may also act as an antioxidant against oxidative
stress.
C
o
l
l
a
g
e
n
S
y
n
t
h
e
s
i
s
•
Most abundant protein found in the body.
•
Vitamin C is necessary for collagen synthesis.
•
Collagen is a structural protein found in skin, bones, tendons, and
cartilage.
•
All collagen (n~19) have a triple helical structure.
•
For the collagen molecule to aggregate into its triple-helix
configuration selected
proline
residues must be
hydroxylated
forming
hydroxyproline.
•
Requires
di-oxygenase enzymes
, reduced iron (Fe+2), ascorbate.
•
Vitamin C role
:
•
During hydroxylation, iron cofactor in the enzymes is oxidized,
(ferrous(2+) state ---- ferric (3+) state).
•
Ascorbate is needed to function as a reductant thereby reducing iron
back to its ferrous (2+) in prolyl and lysyl hydroxylases.
C
o
l
l
a
g
e
n
S
y
n
t
h
e
s
i
s
•
Vitamin C may also influence
mRNA levels
needed for collagen synthesis.
•
Although these reactions may seen simple,
normal development and maintenance of
skin, tendons, cartilage, bone and dentine
depend on an adequate supply of vitamin C.
•
Also, important in
wound healing
and
bleeding
prevention
from capillaries.
C
o
l
l
a
g
e
n
S
y
n
t
h
e
s
i
s
C
a
r
n
i
t
i
n
e
s
y
n
t
h
e
s
i
s
Carnitine
is a methylated from nitrogen containing
compound made from lysine.
•
Sufficient carnitine is
critical in fat metabolism
,
because it is essential to transport long- chain
fatty acids from cell cytoplasm into
mitochondrial
matrix where
β
-oxidation
occurs.
Vitamin C role:
•
Required for
2
hydroxylation reaction in synthesis
carnitine, which functions as preferred reducing
agent, specifically reducing
Fe
from ferric
(Fe
3+
)
back to ferrous state
(Fe
2+
).
T
y
r
o
s
i
n
e
s
y
n
t
h
e
s
i
s
&
c
a
t
a
b
o
l
i
s
m
•
Tyrosine synthesis
•
Hydroxylation of phenylalanine
•
Requires phenylalanine
mono-oxygenase
(hydroxylase),
Fe
+2
. O2. tetrahydrobiopterin, NADPH,
vitamin C
•
Vitamin C regenerating tetrahydro-biopterin from
dihydrobiopterin.
•
Occurs in
liver
and
kidney.
•
Tyrosine catabolism
require ascorbate as reductant for
hydroxylases
•
Cu
-dependent enzyme p-hydroxyphyenylpyruvate
(dioxygenase)
•
Fe
-dependent enzyme homogentisate dioxygenase.
N
e
u
r
o
t
r
a
n
s
m
i
t
t
e
r
s
y
n
t
h
e
s
i
s
•
Vitamin C
maintains mineral cofactors
for some
of the enzymes involved in synthesis of
neurotransmitters in its reduced state.
Norepinephrine
•
It is generated from hydroxylation of dopamine
side chain.
•
This reaction catalyzed by dopamine
monoxygenase (contain
8 Cu
atoms)-vitamin C-
dependent reaction.
•
Found in
nervous tissue
and
adrenal medull
.
D
o
p
a
m
i
n
e
H
y
d
r
o
x
y
l
a
s
e
N
e
u
r
o
t
r
a
n
s
m
i
t
t
e
r
s
y
n
t
h
e
s
i
s
•
Serotonin
•
Hydroxylation of tryptophan (in brain)
•
Requires tryptophan mono-oxygenase (hydroxylase),
O
2
tetrahydrobiopterin, vitamin C. first step in
serotonin synthesis.
•
Other Neurotransmitters and Hormones
•
keeping Cu in reduced for peptidylgycine
α
-amidating
mono-oxygenase.
•
Many of amidated peptides are active as hormones,
such as
calcitonin, CCK
and
gastrin
.
•
The enzyme found in pituitary , adrenal, thyroid glands
and brain.
S
u
m
m
a
r
y
•
Vitamin C acts
as
an electron donor
for
8 different
enzymes
:
•
Three
enzymes participate in
collagen
hydroxylation.
•
Two
enzymes are necessary for synthesis of
carnitine
.
•
Three
remaining enzymes have the following functions
in common, but have other functions as well:
•
Dopamine
β
-hydroxylase participates in biosynthesis of
norepinephrine
from dopamine.
•
Enzyme
adds amide
groups to peptide hormones.
•
One modulates tyrosine metabolism.
M
i
c
r
o
s
o
m
a
l
m
e
t
a
b
o
l
i
s
m
•
A group of enzymes makes up a microsomal
metabolizing system, mostly function in liver,
to
inactivate
both endo-and exogenous substances.
•
Endogenous:
Include various
hormones
and
steroids
(cholesterol)
•
Exogenous:
xenobiotics (foreign chemicals) drugs,
carcinogens, pesticides, pollutants, food additives
•
The reactions to metabolize these substances
usually involve
hydroxylation's
followed by other
reactions to produce polar metabolites for
excretion.
A
n
t
i
o
x
i
d
a
n
t
s
a
c
t
i
v
i
t
y
•
The
reduction potential of ascorbate
is such that it
readily donates electrons/hydrogen ions to regenerate
other antioxidants, such as
vitamin E, glutathione
, and
uric acid, and to
reduce numerous reactive oxygen
(ROS) and nitrogen species (RNS).
•
Ascorbic acid interact with oxidants in the aqueous
phase (blood or intracellular) before they initiate
damage in nucleus, cell lipids.
•
Ascorbate = thiols > bilirubin > uric acid > vitamin E
P
r
o
-
o
x
i
d
a
n
t
a
c
t
i
v
i
t
y
•
Vitamin C can
reduce transition metals
, while
itself becoming oxidized to
semidehydroascorbate:
Ascorbate
(AH
2
) +Fe
3+
or Cu
2-
Semidehydroascorbate radical (AH
−
) + Fe
2+
or Cu
1+
•
These reduced metal ions can cause
cell damage
by
generating ROS and free radicals.
Fe
2+
or Cu
1+
+ H
2
O
2
Fe
3+
or Cu
2-
+ H
2
O
2
+ OH
Fe
2+
or Cu
1+
+ O
2
Fe
3+
or Cu
2-
+ O
2-
O
t
h
e
r
f
u
n
c
t
i
o
n
s
•
Vitamin C and colds:
Vitamin C is thought to moderate colds by
enhancing many immune cell
(such as some
leukocyte) functions while also
destroying
histamine
, which causes many of a
cold’s
symptoms.
O
t
h
e
r
f
u
n
c
t
i
o
n
s
•
Vitamin C and cancer:
•
It is controversial issue due to:
•
Epidemiological studies
suggest inverse relationship
between vitamin C and cancers of oral cavity,
esophagus and stomach.
•
Clinical studies:
•
Some shown that survival time in cancer time patients
may be prolonged, possible protective mechanisms
•
Ability to act as a reducing agent
•
Detoxify carcinogens.
O
t
h
e
r
f
u
n
c
t
i
o
n
s
•
CVD:
•
Many (but not all) epidemiological and prospective studies
report that
increased fruit and vegetable intake, vitamin C
intake
, and
plasma vitamin C concentration
are
associated
with
decreased
risk of heart disease.
•
Low vitamin C
status also is
related
to
increased blood
total cholesterol concentrations
, whereas high plasma
vitamin C concentrations have been associated with lower
blood pressure and with higher plasma high-density
lipoprotein cholesterol concentrations, both of which are
protective against heart disease.
•
studies with
supplements of vitamin C
and other
antioxidants have not reported beneficial effects.
O
t
h
e
r
f
u
n
c
t
i
o
n
s
•
Cataracts
:
negative relation with vitamin c
•
Bone density:
Positive relation with vitamin C
•
Wound healing
and connective tissue
metabolism.
I
N
T
E
R
A
C
T
I
O
N
S
W
I
T
H
O
T
H
E
R
N
U
T
R
I
E
N
T
S
•
Vitamin C and
iron
•
Increase intestinal absorption of
non-heme iron
•
Reduce Fe
3+
to Fe
2-
forms a soluble complex with
iron in alkaline pH of SI.
•
Effect on
iron distribution
in the body.
•
Vitamin C aids incorporation of iron into ferritin
•
Excessive iron in presence of vitamin C can
accelerate oxidative catabolism of vitamin C.
I
n
t
e
r
a
c
t
i
o
n
s
w
i
t
h
o
t
h
e
r
n
u
t
r
i
e
n
t
s
•
Vitamin C and copper
•
May
increase absorption
and
excretion
of
heavy
metals
•
Vitamin C intakes above 600 mg/d may
interfere
with
copper metabolism
.
•
Vitamin C helps keep
folate
in its reduced and
active form.
E
x
c
r
e
t
i
o
n
•
Excretion reduced when intake is low
•
Urinary excretion
•
Body pool <1.500mg leads to only metabolites
in urine
•
Body pool > 1500mg leads to proportionately
more ascorbate in urine
•
Vitamin C may be excreted intact or oxidized
by L-ascorbate oxidase to oxalic acid, primarily
in liver and some in kidney.
V
i
t
a
m
i
n
C
R
D
A
•
Adult male: 90mg
•
Adult female: 75 mg
•
Pregnancy: 100my
•
Lactating: 120mg
•
Smokers: extra 35 mg
•
UL: adult 2000 mg.
D
e
f
i
c
i
e
n
c
y
•
Scurvy
•
Scurvy leads to
formation of brown spots on skin
,
bleeding gums
,
small red skin discolorations
caused by ruptured small blood vessels
(
petechiae
), sublingual hemorrhages, easy
bruising (ecchymoses and purpurae),
impaired
wound
and fracture healing, joint pain
(arthralgia),
loose and decaying teeth
, and
hyperkeratosis of hair follicles, especially on the
arms, legs, and buttocks.
S
c
u
r
v
y
T
o
x
i
c
i
t
y
•
Toxicity is
rare
.
•
Tolerable upper intake level of
2g vitamin C/d
•
The most common side effect with ingestion of
large amounts (2 g) of the vitamin is
gastrointestinal problems
characterized by
abdominal pain and osmotic diarrhea
.
•
Other side effects include increased risk of
kidney
stones and iron toxicity
for those with renal
disease and disorders of
iron metabolism
.
Vitamin C, also known as ascorbic acid, is essential for humans as they cannot synthesize it internally. Its history, sources, sensitivity, and importance in digestion, absorption, and transport are discussed. Sources of vitamin C include fruits, vegetables, and organ meats. The sensitivity of vitamin C to various factors like cooking and exposure is highlighted. Learn more about the structure and significance of vitamin C through this comprehensive guide.
Uploaded on Sep 27, 2024 | 0 Views
Download Presentation
Please find below an Image/Link to download the presentation.
The content on the website is provided AS IS for your information and personal use only. It may not be sold, licensed, or shared on other websites without obtaining consent from the author. Download presentation by click this link. If you encounter any issues during the download, it is possible that the publisher has removed the file from their server.
E N D
Presentation Transcript
Vitamin C Vitamin C also known as ascorbic acid or ascorbate. The human being is one of the few mammals unable to synthesize vitamin C. Other animals unable to synthesize vitamin C include primates, fruit bats, guinea pigs, and some birds. The inability to synthesize vitamin C results from the lack of gulonolactone oxidase, the last enzyme in the vitamin C synthetic pathway.
History of Vitamin C Vitamin C was isolated in 1928, and its structure was determined in 1933. The problems referred to as scurvy and associated with the lack of vitamin C had been quite prevalent for centuries. Some of the most notable stories are those of the British sailors who often died from scurvy on sea.
Vitamin C Vitamin C have a number of vitamiers that have vitamin C activity in animals: Ascorbic acid in biological system (low pH) Oxidized form deyhroascorbic acid. Ascorbate in neutral salutation (pH>5) Ascorbate and ascorbic acid are both naturally present in the body, since the forms interconvert according to pH.
Sources Fruits, vegetables and organ meats (liver, kidney). The best food sources of vitamin C include asparagus, papaya, oranges, cantaloupe, cauliflower, broccoli, green peppers, grapefruit, grapefruit, lemons, and strawberries. Citrus products are most commonly cited as significant sources of the vitamin. Supplements supply vitamin C typically as free ascorbic acid, calcium ascorbate, sodium ascorbate, and ascorbyl palmitate.
Sensitivity of vitamin C Very significant losses occur as vegetables wilt, or when they are cut, as a result of the release of ascorbate oxidase from the plant tissue. Significant losses of the vitamin also occur in cooking, both through leaching into the cooking water and also atmospheric oxidation, which continues when foods are left to stand before serving.
DIGESTION, ABSORPTION & TRANSPORT Vitamin C does not require digestion prior to being absorbed into intestinal cells. There is active transport of the vitamin at the intestinal mucosal brush border membrane. Both ascorbate and dehydroascorbate are absorbed across the buccal mucosa by carrier-mediated passive processes. Intestinal absorption of dehydroascorbate is carrier mediated, followed by reduction to ascorbate before transport across the membrane.
DIGESTION, ABSORPTION & TRANSPORT Prior to absorption, ascorbic may be oxidized to dehydroascorbate, which may be absorbed by facilitated diffusion. Although dehydroascorbic acid is absorbed in higher rate than ascorbate, the amount of dehydroascorbic acid found in plasma and tissues under normal conditions is low, as cells rapidly reduce dehyroascorbic acid to ascorbate.
DIGESTION, ABSORPTION & TRANSPORT Simple diffusion (may occur in stomach and small intestine) provides for vitamin C absorption with ingestion of higher amounts of the vitamin. Anion channels in some cells may mediate vitamin C diffusion faster than the transporters. From intestinal cells, ascorbate may diffuses through anion channels into extracellular fluid and enters plasma by way of capillaries.
DIGESTION, ABSORPTION & TRANSPORT Within intestinal cells: Dehydroascorbic acid is rapidly reduced back to ascorbic acid by enzyme dehydroascorbate reductase. Glutathione (GSH), which is required for the reduction of dehydroascorbate, is oxidized in process. Glutathione spares vitamin C and, in general, improves the antioxidant protection capacity of blood. Degree of vitamin C absorption decrease with increased vitamin intake.
DIGESTION, ABSORPTION & TRANSPORT Some 80 95% of dietary ascorbate is absorbed at usual intakes (up to about 100 mg/day). The fractional absorption of larger amounts of the vitamin is lower, and unabsorbed ascorbate from very high doses is a substrate for intestinal bacterial metabolism, causing gastrointestinal discomfort and diarrhea.
DIGESTION, ABSORPTION & TRANSPORT Absorption of ascorbate may be diminished in the presence of high intracellular glucose, which appears to interfere with ascorbate transporter. Unabsorbed vitamin C may be metabolized by intestinal flora. Ingesting large amounts of iron with vitamin C may result in oxidative destruction of vitamin C in digestive tract, yielding other products without vitamin C activity.
DIGESTION, ABSORPTION & TRANSPORT In plasma: Ascorbic acid is transported in the plasma primarily in free form as an ascorbate anion. Normal plasma level of vitamin C 0.4 1.7 mg/dL. In cells: Uptake of ascorbate into body cells requires sodium and a carrier and into some cells such as leukocytes, uptake is also energy dependent. Tissue concentrations of vitamin C usually exceed plasma concentrations.
DIGESTION, ABSORPTION & TRANSPORT Ascorbate and dehydroascorbate concentrations are much greater in some tissues than others. The highest in adrenal and pituitary glands (~30-50mg/100 g of wet tissue). Intermediate in liver, spleen, heart, kidneys, lungs pancreas and leukocytes. Smaller amounts in muscles and red blood cells. Maximal vitamin C pool is estimated at about 1.500mg. Intakes of about 100-200mg vitamin C/d have been shown to produce plasma concentrations of about 1.0mg/dL and to maximize body pool.
Summary of absorption Absorbed in the intestine by an energy-requiring, sodium- dependent, carrier- mediated transport system. After absorption, ascorbic acid is then transported as a free acid in plasma into the cells, including leukocytes and red blood cells. In the tissues, Vitamin C serves as an electron donor for a number of enzymes.
Function & mechanism of action Vitamin C has very complex functional roles in the body as a cofactor in around eight reactions: 1. Collagen synthesis 2. Carnitine synthesis 3. Tyrosine synthesis and catabolism 4. Neurotransmitter synthesis. 5. Drug and steroid metabolism. 6. Maintain the iron and copper atoms in the metalloenzymes in the reduced state. 7. In addition vitamin C acting role as reducing agent in enzymatic reactions. 8. Ascorbate may also act as an antioxidant against oxidative stress.
Collagen Synthesis Most abundant protein found in the body. Vitamin C is necessary for collagen synthesis. Collagen is a structural protein found in skin, bones, tendons, and cartilage. All collagen (n~19) have a triple helical structure. For the collagen molecule to aggregate into its triple-helix configuration selected proline residues must be hydroxylated forming hydroxyproline. Requires di-oxygenase enzymes, reduced iron (Fe+2), ascorbate. Vitamin C role: During hydroxylation, iron cofactor in the enzymes is oxidized, (ferrous(2+) state ---- ferric (3+) state). Ascorbate is needed to function as a reductant thereby reducing iron back to its ferrous (2+) in prolyl and lysyl hydroxylases.
Collagen Synthesis Vitamin C may also influence mRNA levels needed for collagen synthesis. Although these reactions may seen simple, normal development and maintenance of skin, tendons, cartilage, bone and dentine depend on an adequate supply of vitamin C. Also, important in wound healing and bleeding prevention from capillaries.
Carnitine synthesis Carnitine is a methylated from nitrogen containing compound made from lysine. Sufficient carnitine is critical in fat metabolism, because it is essential to transport long- chain fatty acids from cell cytoplasm into mitochondrial matrix where -oxidation occurs. Vitamin C role: Required for 2 hydroxylation reaction in synthesis carnitine, which functions as preferred reducing agent, specifically reducing Fe from ferric (Fe3+ ) back to ferrous state (Fe2+ ).
Tyrosine synthesis & catabolism Tyrosine synthesis Hydroxylation of phenylalanine Requires phenylalanine mono-oxygenase (hydroxylase), Fe+2. O2. tetrahydrobiopterin, NADPH, vitamin C Vitamin C regenerating tetrahydro-biopterin from dihydrobiopterin. Occurs in liver and kidney. Tyrosine catabolism require ascorbate as reductant for hydroxylases Cu-dependent enzyme p-hydroxyphyenylpyruvate (dioxygenase) Fe-dependent enzyme homogentisate dioxygenase.
Neurotransmitter synthesis Vitamin C maintains mineral cofactors for some of the enzymes involved in synthesis of neurotransmitters in its reduced state. Norepinephrine It is generated from hydroxylation of dopamine side chain. This reaction catalyzed by dopamine monoxygenase (contain 8 Cu atoms)-vitamin C- dependent reaction. Found in nervous tissue and adrenal medull.
Neurotransmitter synthesis Serotonin Hydroxylation of tryptophan (in brain) Requires tryptophan mono-oxygenase (hydroxylase), O2 tetrahydrobiopterin, vitamin C. first step in serotonin synthesis. Other Neurotransmitters and Hormones keeping Cu in reduced for peptidylgycine -amidating mono-oxygenase. Many of amidated peptides are active as hormones, such as calcitonin, CCK and gastrin. The enzyme found in pituitary , adrenal, thyroid glands and brain.
Summary Vitamin C acts as an electron donor for 8 different enzymes: Three enzymes participate in collagen hydroxylation. Two enzymes are necessary for synthesis of carnitine. Three remaining enzymes have the following functions in common, but have other functions as well: Dopamine -hydroxylase participates in biosynthesis of norepinephrine from dopamine. Enzyme adds amide groups to peptide hormones. One modulates tyrosine metabolism.
Microsomal metabolism A group of enzymes makes up a microsomal metabolizing system, mostly function in liver, to inactivate both endo-and exogenous substances. Endogenous: Include various hormones and steroids (cholesterol) Exogenous: xenobiotics (foreign chemicals) drugs, carcinogens, pesticides, pollutants, food additives The reactions to metabolize these substances usually involve hydroxylation's followed by other reactions to produce polar metabolites for excretion.
Antioxidants activity The reduction potential of ascorbate is such that it readily donates electrons/hydrogen ions to regenerate other antioxidants, such as vitamin E, glutathione, and uric acid, and to reduce numerous reactive oxygen (ROS) and nitrogen species (RNS). Ascorbic acid interact with oxidants in the aqueous phase (blood or intracellular) before they initiate damage in nucleus, cell lipids. Ascorbate = thiols > bilirubin > uric acid > vitamin E
Pro-oxidant activity Vitamin C can reduce transition metals, while itself becoming oxidized to semidehydroascorbate: Ascorbate (AH2) +Fe3+or Cu2- Semidehydroascorbate radical (AH ) + Fe2+ or Cu1+ These reduced metal ions can cause cell damage by generating ROS and free radicals. Fe2+ or Cu1++ H2O2 Fe3+or Cu2-+ H2O2 + OH Fe2+ or Cu1++ O2 Fe3+or Cu2-+ O2-
Other functions Vitamin C and colds: Vitamin C is thought to moderate colds by enhancing many immune cell (such as some leukocyte) functions while also destroying histamine, which causes many of a cold s symptoms.
Other functions Vitamin C and cancer: It is controversial issue due to: Epidemiological studies suggest inverse relationship between vitamin C and cancers of oral cavity, esophagus and stomach. Clinical studies: Some shown that survival time in cancer time patients may be prolonged, possible protective mechanisms Ability to act as a reducing agent Detoxify carcinogens.
Other functions CVD: Many (but not all) epidemiological and prospective studies report that increased fruit and vegetable intake, vitamin C intake, and plasma vitamin C concentration are associated with decreased risk of heart disease. Low vitamin C status also is related to increased blood total cholesterol concentrations, whereas high plasma vitamin C concentrations have been associated with lower blood pressure and with higher plasma high-density lipoprotein cholesterol concentrations, both of which are protective against heart disease. studies with supplements of vitamin C and other antioxidants have not reported beneficial effects.
Other functions Cataracts: negative relation with vitamin c Bone density: Positive relation with vitamin C Wound healing and connective tissue metabolism.
INTERACTIONS WITH OTHER NUTRIENTS Vitamin C and iron Increase intestinal absorption of non-heme iron Reduce Fe3+ to Fe2-forms a soluble complex with iron in alkaline pH of SI. Effect on iron distribution in the body. Vitamin C aids incorporation of iron into ferritin Excessive iron in presence of vitamin C can accelerate oxidative catabolism of vitamin C.
Interactions with other nutrients Vitamin C and copper May increase absorption and excretion of heavy metals Vitamin C intakes above 600 mg/d may interfere with copper metabolism. Vitamin C helps keep folate in its reduced and active form.
Excretion Excretion reduced when intake is low Urinary excretion Body pool <1.500mg leads to only metabolites in urine Body pool > 1500mg leads to proportionately more ascorbate in urine Vitamin C may be excreted intact or oxidized by L-ascorbate oxidase to oxalic acid, primarily in liver and some in kidney.
Vitamin C RDA Adult male: 90mg Adult female: 75 mg Pregnancy: 100my Lactating: 120mg Smokers: extra 35 mg UL: adult 2000 mg.
Deficiency Scurvy Scurvy leads to formation of brown spots on skin, bleeding gums, small red skin discolorations caused by ruptured small blood vessels (petechiae), sublingual hemorrhages, easy bruising (ecchymoses and purpurae), impaired wound and fracture healing, joint pain (arthralgia), loose and decaying teeth, and hyperkeratosis of hair follicles, especially on the arms, legs, and buttocks.
Toxicity Toxicity is rare. Tolerable upper intake level of 2g vitamin C/d The most common side effect with ingestion of large amounts (2 g) of the vitamin is gastrointestinal problems characterized by abdominal pain and osmotic diarrhea. Other side effects include increased risk of kidney stones and iron toxicity for those with renal disease and disorders of iron metabolism.
