1

History
1601 Europe sailors regular consumption of citrus
fruits or juice prevent the disease, known as scurvy.
1907 Eijkman, Holst & Frolich (Oslo) animal
model, to produce beri beri disease, but failed
familiar signs of scurvy
1910 Zilfa & colleag. isolate from lemon the crude
factor that had come to be known as vitamin C.
1926 1932 structure determined Szent-Gyrgi
(Hungary) & King (Pittsburg Univ.) the anti-scorbutic
factor was identical with the reductant hexuronic acid,
now called ascorbic acid & isolated in crystalline form
from adrenal cortex; cabbage; citrus juice.
2
Chemistry & Structure
Ascorbic acid
= ascorbate
= vitamin C
6-carbon lactone

3
Chemistry & Structure

Ascorbic acid; monodehydroascorbic acid & dehydroascorbic

acid compose a reversible redox system
An effective quencher of free radicals, such as singlet oxygen
(1O2).
Reduces Ferric (Fe3+) to Ferrous (Fe2+) iron; superoxide radicals
(O2.-) to H2O2 from the process ascorbic acid is oxidized to
monodehydroascorbic acid.
4
Vitamin C
Vitamin C (L-ascorbic acid & its reduced form, dehydroascorbic acid) is
a water-soluble vitamin
Best-defined function is as a cofactor for the enzyme required in the
hydroxylation of proline and lysine in collagen formation(*).
Other function :
As an antioxidant (*)
As a cofactor in other reaction (H+/ e- Donors/ Acceptors)
Hydroxylation of carnitine (*)

Metabolism of tyrosine. (*)

Metabolism of NT (*)

Metabolism of drug & steroid (*)

Metal ion metabolism (*)

Antihistamine reactions & Immune functions. (*)
It can be synthesized from glucose by many mammals, but not by
humans (because lack of gulonolactone oxidase), through Gulonic acid
pathways (*).
5
Sources
The highest vitamin C content is found in
Fruits (esp. cantaloupe, kiwi, oranges, citrus fruits, strawberries,
watermelon)
Vegetables (esp. broccoli, green & red pepper, cauliflower,
Brussels sprouts, asparagus, potatoes, cabbage, collard greens,
green peas, carrots)
Fruit juice (esp. orange & grapefruit)
Vegetable juice (esp. tomato)
And leafy greens such as spinach, turnip, and mustard greens.

Losses of vitamin C cooked in large amounts of water, exposed

to extensive heating, or exposed to air.

6
 Bioavailability
Biological activities of vitamin C in foods >>
purified L-ascorbic acid.
Synthetic ascorbic acids derivates (ascorbate
polyphosphate) have vit. C activities &
superior chemical stability.
More highly biopotent appear to be effectively
hydrolized in the digestive tract & tissue.

7
Absorption
Cannot synthesize ascorbic acids absorb
by transport active (Na+), in Ileum.
The efficiency of absorption 80 90% if in
physiological dose ( < 180 mg/day).
The efficiency of absorption declines at dose
greater than 1 g (75%).

8
Transport of Vit.C
In reduce form (ascorbic acid), free in the plasma.
Cellular uptake by :
Transport active (Na+) & (energy) transporter
Glucose transporter
Insulin promote the cellular uptake of
dehydroascorbic acid & glucose inhibit it.
Tissue distribution predominant storage form :
ascorbic acid. Depots in adrenals, leucocytes.
Respons in stress decrease in tissue levels.

9
 Vitamin C Metabolism

Oxidation

Asam dehidroaskorbat hidrolisis lanjut yg irreveribel asam 2,3-

diketo-L-gulonat
dekarboksilasi mjd CO2 & fragmen 5-C (xylose, xyonic acid, lyxonic
acid), atau
oksidasi mjd asam oksalat & fragmen 4-C (mis.asam threonat).

Ekskresi
Bbg metabolit urin
Asam oksalat
Asam askorbat & asam dehydroaskorbat
Asam diketogulonat
Askorbat 2-sulfat
Konsumsi vitamin > 500 mg/hr semua asam askorbat di atas level
tsb akan dibuang mell urin, tanpa diubah tidak meningkatkan 10

simpanan askorbat dlm tubuh.

Biochemical Functions
Electron transport (lih.ttg sintesis kolagen)
Antioxidant function (mereduksi metal ion)
Prooxidant properties (asam askorbat dosis tinggi, stlh mereduksi
metal ion, bereaksi dg O2 utk mbentuk radikal oksigen, yg akan
mengoksidasi kembali metal ion)
Enzyme Cosubstrate Function
Collagen synthesis
Neurotransmitter Metabolism
Carnitine synthesis
Drug & Streoid Metabolism
Tyrosine Metabolism
Metal Ion Metabolism
Antihistamine Reactions
Immune Functions
Health effects (*)

11
Deficiency

Scurvy (at adults)

Defect in collagen formation
Hemorrhage
Weakening of collagenous structures in bone,
cartilage, teeth & connective tissues.
Moeller Barlow disease (in children, non-breast-fed
infants)
Widening of bone-cartilage boundaries (rib).
Stressed epiphyseal cartilages of extremities
Severe joint pain
Anemia & fever

12
Toxicity
Efek dari iklan utk mengkonsumsi vit. C megadosis
setiap hari.
Efek negatif yg mungkin muncul :
Peningkatan ekskresi oksalat batu ginjal.
Hambatan kompetitif reabsorbsi asam urat di ginjal.
Peningkatan perombakan vit. B12 dalam usus.
Peningkatan absorbsi besi non-heme (iron overload).
Efek mutagenik
Peningkatan katabolisme askorbat (yg menetap
walaupun asupan vit. C dikurangi)

13
14
Collagen Formation (*)
Prolyl 4-hydroxylase
Prolyl 3-hydroxylase
Lysil hydroxylase
Mrpk enzim hydroxylase yg
mengandung Fe.
Ascorbate diperlukan utk
mempertahankan besi dlm
status tereduksi (Fe2+).
P h & L h utk modifikasi
prokolagen (proline & lysine)
dlm pembentukan kolagen.
P h modifikasi prekursor
protein osteocalcin &
komponen komplemen C1q.

15
VITAMIN C ANTIOKSIDAN (*)

Antioxidant
a non-enzymatic reductive function based on its
action as an electron donor in chemical reactions
(ascorbate is a reducing agent).
ability to react with free radicals;
(Asam askorbat melepaskan 2 H & 2 elektron, kmd mjd asam
dehidroaskorbat. Asam dehidroaskorbat bersifat sangat mudah
menerima H utk kembali mjd asam askorbat)
Asam askorbat bereaksi dg toxic-reactive oxygen
species, yi. Superoxide anion (O2.-) & hydroxyl
radical (OH.).
. elektron yg tdk memiliki pasangan.
16
CARNITINE (*)

Trimethyllysine hydroxylase
dioksigenase
-butyrobetaine hydroxylase
Mrpk enzim hydroxylase yg mengandung Fe.
Diperlukan dlm sintesis carnitine.
Carnitine for the transport of fatty acid into
mitochondria for oxidation to provide energy for the
cell.
(metabolisme asam lemak)

17
TYROSINE METABOLISM (*)
4-hydroxyphenylpyruvate dioxygenase
Homogentisate 1,2-dioxygenase
Mrpk iron-containing hydroxylase
Vitamin C involved in the oxidative
degradation of tyrosine.
Catalyzes the oxidation & decarboxilation of
the intermediate of tyrosine degradation to
homogentisic acid.
Deficiency of vit. C impairs the reactions
tyrosinemia. 18
Metabolism of Neurotransmitter (*)
Ascorbic acid serves as an electron donor for :
1. Dopamine -hydroxylase = Dopamine -monooxygenase
Cu+ -containing hydroxylase
Located in chromaffin vesicles adrenal medulla & in
adrenergic synapses.
Hydroxillates dopamin NT norepinephrine
Cu+, slm proses hidroksilasi substrat, teroksidasi mjd Cu2+ ;
Cu2+ direduksi kembali mjd Cu+ o/ askorbat, sdgkan
askorbat teroksidasi mjd monodehydroaskorbat.
2. Peptidylglycine -Amidating Monooxygenase (PAM) =
Peptidylglycine hydroxyilase
Cu+ -containing hydroxylase
Catalyze the amidation of peptides hormone, require
ascorbate & O2.
19
Drug & Steroid Metabolism (*)
Ascorbic acid involved in microsomal hydroxylation reactions of
drug & steroid metabolism those coupled to the microsomal
electron transport chain. as coenzyme in cytochrome P-450-
dependent oxidations.
Epidemiologic studies significant positive correlation of
ascorbic acid & HDL-cholesterol in the plasma.
Deficiency of vit. C impairs the hydroxylation, demethylation
significant increases the half-lives some drugs.
(phenobarbital, acetanilide, aniline, antipyrine).
Animals deficient of vit. C have diminished plasma
glucocorticoid respons when stress occurs synthesis of
corticosteroids reduce.

20
Metal Ion Metabolism (*)
Increases the bioavailability of iron in foods (heme
iron & non heme iron).
Non-heme iron Reduction of ferric form (Fe 3+) to
the ferrous form (Fe 2+) well absorbed.

Promotes utilization of heme iron enhanced

incorporation of iron into its intracellular storage form,
ferritin, & enhances the stability of ferritin.
Other metallic elements selenium, nickel, lead,
vanadium, & cadmium).

21
(*)
Reaksi Antihistamine
Bersama dg Cu+ menghambat pelepasan
histamin, & mempercepat degradasi
histamin.
Fungsi Imunitas
Mstimulasi produksi interferon
Mstimulasi kemotaksis & proliferasi netrofil
Mstimulasi sintesis faktor tymus humoral &
antibodi IgG & IgM.

22
Biosynthesis of Vitamin C (*)

23
HEALTH EFFECTS (*)
Fungsi Imun
Antioksidan thd produk
oksidan yg dihasilkan oleh
sel fagosit.
Penyembuhan Luka
Sintesis kolagen.
Penyakit Kardiovaskuler
Sbg agen antiatherogenik
dlm mengurangi oksidasi
LDL.
Diabetes
Vit.C mengurangi glikosilasi
protein plasma.
Suplementasi 100mg/hr
mengurangi akumulasi
sorbitol eritrosit. [sorbitol :
terlibat patologi komplikasi
diabetes]
Katarak
Vit.C mcegah oksidasi
lensa yg terpapar sinar UV.
Fungsi Paru Paru
Vit.C sbg antioksidan thd
oksigen & gas gas toksik
yg terinhalasi; sel sel
inflamasi pd org asma.
Produksi surfaktan (mirip
sint.kolagen)
Kanker
Mencegah ikatan DNA dg
polycyclic aromatic
carcinogen.
Me-blok p,bentukan
Nitrosamin
24
Biosintesis vit C

25
26
27