METABOLISME

VITAMIN B12, B9, & C

Ayu Rahadiyanti
Outline

1 Metabolisme Vitamin B12

2 Metabolisme Vitamin B9

3 Metabolisme Vitamin C
 Water-soluble
vit

Vit B-complex Vit C

Energy
releasing : B1, Hemapoietic : Other : B1, B3,
B2, B3, B5, B6, B5, B6, B9, B12 B6, B9, B12
B7
VITAMIN B12
Vitamin B12 (kobalamin)  gol
korinoid (senyawa yg mengandung
kobalt yg memiliki cincin korin dg
aktivitas biologis vitamin.
Sebagian korinoid mrpk faktor per-
tumbuhan bagi mikroorganisme yg
memiliki aktivitas vit B12, antime-
tabolit thd vit.
 Sumber Vit B12
• Vitamin B12 is ubiquitous in foods of
animal origin and is derived from the
animal’s ingestion of cobalamin-containing
animal tissue or microbiologically contami-
nated plant material, in addition to vitamin
absorbed from the animal’s own digestive
tract.
• Liver is the outstanding dietary source of
the vitamin, followed by kidney and heart.
Muscle meats, fish, eggs, cheese and milk
are other important food sources.
 Absorbsi Vit B12

Vitamin B12 diserap dlm keadaan teri-

kat pd faktor intrinsik (glikoprotein yg
disekresikan oleh sel parietal mukosa
lambung).
Asam lambung dan pepsin
membebaskan vit dr ikatan dg protein
dlm mkn dan menyebabkan vit
berikatan dg Haptocorin/
kobalofilin/TC-1.
Di duodenum, kobalofilin mengalami
hidrolisis shg vit dibebaskan utk
berikatan dg faktor intrinsik.
Vit B12 diabsorpsi di 1/3 distal ileum
melalui resptor yg mengikat kompleks
faktor intrinsik-vit B12 tp tdk mengikat
faktor intrinsik/vit dlm bentuk bebas.
50 – 90% vit. B12 akan diperoleh dan disimpan dlm hati. 0,1
– 0,2% dibuang melalui empedu.
Dalam plasma diikat protein transkobalamin II pengangkutan
dan pengambilan oleh hati dan jar.hematopoietik.
Dua bentuk kobalamin sbg koenzim pd manusia :
Metil kobalamin (sitosol)  konversi homosistein mjd metionin,
konversi metil tetra hidrofolat mjd tetrahidrofolat (THF).
5-deoksiadenosil kobalamin (mitokondria) konversi metil malonil-
CoA mjd suksinil-CoA dlm proses glukoneogenesis.
 Enzim Dependen Vitamin B12

Enzyme Metabolic function

Methylmalonyl-coA Conversion of methylmalonyl-coA to succinyl-coA
mutase in the degradation of propionate

L-α-Leucine mutase Conversion of L-α-Leucine to aminoisocapronate

as the first step in the synthesis/degradation of
the amino acid
Methionine synthase Methylation of homocysteine to produce methio-
nine, serving as the methyl group carrier between
the donor-5-methyl-FH4 and the acceptor
homocysteine
L-Methylmalonyl-CoA mutase
requires adenosylcobalamin
for the conversion of L-
methylmalonyl-CoA to
succinyl-CoA, an
important intermediary in the
tricarboxylic acid cycle.
Methionine synthase, uses the chemical form of
the vit which has a methyl group attached to the
cobalt and is called methylcobalamin. The other
enzyme, methylmalonyl coenzyme (CoA)
mutase, uses a form of vitamin B that has a 5’-
adeoxyadenosyl moiety attached to the cobalt
and is called 5’-deoxyadenosylco-balamin, or
coenzyme B12.
Methionine synthase catalyses the conver-
sion of homocysteine to methionine & rege-
nerates THF. A deficiency of vitamin B lowers
intracellular levels of 5,10-methylene-THF,
which is required for DNA synthesis.
Peran Vitamin B12 dan folat (5-metil THFA)

Pembentukan timidilat (DNA)

Purin (adenin, guanin)

Sintesis protein
Gejala klinis defisiensi : demielinasi menyebar dan progresif 
anemia megaloblastik (cukup plasma tetapi tdk cukup kromatin
untuk pembelahan sel)
 Kebutuhan Vit B12
Rekomendasi asupan vit B12 untuk
dewasa 2,4 µg/hari
RDA 2 – 3 µg/hari. Kebutuhan mening-
kat pd kehamilan, hipertiroidisme, kon- disi
hematopoiesis meningkat.
Pengolahan dpt menurunkan vit. B12
7–30% (perebusan,pasteurisasi susu,
sterilisasi)
Populasi yang berisiko defisiensi vit B12

Vegetarian

• Tanaman tidak mensintesis vitamin B12, individu yg diet vegan berisiko

defisiensi vitamin B12.

Anemia pernisiosa

• Disebabkan kegagalan absorpsi vit B12, gangguan sekresi faktor intrinsik

akibat penyakit autoimun / krn terbentuknya antibodi antifaktor intrinsik,
dikarakteristikkan dg eritrosit yg besar dan immature.

Atrofi gastritis

• Sel lambung mengalami gangguan shg produksi HCl dan faktor intrinsik
berkurang.
Marginal defisiensi vitamin B12 mengganggu kognitif.
Tidak terdapat efek pada kelebihan vit B12.
Dosis hingga 1000 µg tidak menampakkan bahaya, tetapi juga tidak
menunjukkan manfaat.
Upper limit (UL) Vit B12 belum ada.
 ASAM FOLAT
Its primary coenzyme form, tetra
hydrofolate (THF), serves as part of an
enzyme complex that transfers 1-
carbon compounds that arise during
metabolism.
This action converts vit B12 to one its
coenzyme forms, synthe- sizes the DNA
required for all rapidly growing
cells, and rege- ne rates the amino acid
methio- nine from homocysteine.
Sumber Folat
Absorbsi Folat
Enzymes on the intestinal cell surfaces hydrolyze the polyglutamate to
monoglutamate—folate with only one glutamate attached—and several
single glutamates. The monoglutamate is then attached to a methyl
group (CH3) and delivered to the liver and other body cells. To activate fo-
late, the methyl group must be removed by an enzyme that requires the
help of vitamin B12
Without that help,folate becomes trapped inside cells in its methyl form,
unavailable to support DNA synthesis and cell growth.
The liver incorporates excess folate into bile that is then sent to the gall-
bladder and GI tract. Thus folate travels in the same enterohepatic cir-
culation as bile.
Folate is active in cell multiplication-and the cells lining the GI tract are
among the most rapidly replaced cells in the body. When unable to
make new cells, the GI tract deteriorates and not only loses folate, but
fails to absorb other nutrients as well.
 Kebutuhan Folat
Suplemen folat yg diberikan 1 bulan
pra konsepsi dan berlanjut hingga
trimester I kehamilan dpt mencegah
neural tube defects (NTD).
Bioavailabilitas folat 50% dr makanan,
100% dari suplemen saat lambung
kosong.
Kebutuhan folat meningkat selama
kehamilan.
Fungsi folat untuk memecah asam amino homosistein.
Tanpa folat, homosistein terakumulasi, untuk meningkatkan
pembentukan gumpalan darah dan lesi aterosklerotik.
Makanan yg terfortifikasi folat dan suplemen folat dpt menaik
kan kadar folat dan menurunkan homosistein tetapi tdk menu
runkan risiko serangan jantung, stroke, atau kematian akibat
penyebab kardiovaskular.
 Defisiensi Folat

Defisiensi folat dpt mengganggu pembelahan

sel dan sintesis protein. Pd defisiensi folat
penggantian eritrosit dan sel GI
terganggu shg dampaknya yaitu anemia dan
kemunduran sal GI.
Anemia defisiensi folat : anemia makro sitik
atau megaloblastik, yg dikarakteristikkan dg
eritrosit yg besar dan immature.
Defisiensi folat dapat terjadi bila :

Alkoholisme kronis (penurunan absorpsi)

Defisiensi niasin (reduksi asam folat butuh NADPH)
Defisiensi vit B12 (folat terperangkap sbg metil folat  pembentukan metilen THFA
terganggu)
Diet tinggi metionin dan glisin (ketersediaan THFA menurun krn reaksi perubahan
homosistein mjd metionin dan serin mjd glisin terhalang)
Obat
Beberapa medikasi, seperti obat antikanker kemoterapi (methotrexate dan aminopterin 
kompetitif inhibitor) memiliki struktur kimia seperti folat dan dpt menggantikan vitamin dari
enzim dan mengganggu metabolisme normal.
Aspirin dan antasid mengganggu status folat tubuh, aspirin menghambat aksi enzim yg
membutuhkan folat, antasid membatasi absorpsi folat.
Kontrasepsi oral menghambat penggunaan folat (mengganggu pemecahan poliglutamat)
Suplemen folat akan memperbaiki anemia megaloblastik akibat
defisiensi vit B12, namun mempercepat terjadinya kerusakan saraf
(ireversibel) yg ditemukan pd defisiensi vit B12.
Terdapat antagonisme antara asam folat dengan obat antikonvulsan.
Beberapa orang dewasa yg mengkonsumsi suplemen folat dapat
menyebabkan defisiensi vit B12 dan diagnosis gangguan neurologis.
Dosis folat 5 – 10 mg dianggap aman, dianjurkan menghindari
konsumsi >2,5 kali AKG pd bumil.
Upper level folat = 1000 µg/hari
 Category B12 B9
Food Source Animal protein Almost all food
Site of absorption Ileum Jejunum
Mech of absorption Uptake of IF - Deconjugation of poly-
CBL complex Glu
Metabolic Function Unknown One carbon transfer
Body store 2 – 12 years 4 – 5 months
Dietary deficiency Rare Common
Neurologic disease Yes No
 VITAMIN C
Asam askorbat dan dehidroaskorbat
memiliki aktivitas sebagai vitamin.
Vit C parts company with vit B in its
mode of action.
Vit C as a cofactor helping a specific
enzyme peerform its job but in others it
acts as an antioxidant participating in
more general ways.
Sumber Vitamin C
Fungsi Vitamin C

Antioxidant
Vitamin C loses electrons easily, a characteristic that allows it to perform
as an antioxidant. In the body, antioxidants defend against free radicals.
Antioxidants can neutralize free radicals by donating an electron or two.
In the cells and body fluids, vitamin C protects tissues from the oxida-
tive stress of free radicals and thus may play an important role in
preventing diseases. In the intestines, vitamin C enhances iron absorp-
tion by protecting iron from oxidation.
Cofactor in Collagen Formation
Vitamin C helps to form the fibrous structural protein of connective tissue
known as collagen. During the synthesis of collagen, proline or lysine is
added to the growing protein chain, an enzyme hydroxylates it, making
the amino acid hydroxyproline or hydroxylysine. The conversion of
proline to hydroxyproline requires vit C and Fe.
Cofactor in Other Reactions
Vit C helps in the hydroxylation of carnitine, a compound that transports
fatty acids, across the inner membrane of mitochondria in cells. It also
participates in the conversions of the tryptophan and tyrosine to the
neurotransmitters serotonin and norepinephrine. Vit C also assists in the
making of hormones, including thyroxine, which regulates the metabolic
rate when metabolism speeds up in times of extreme physical stress, the
body’s use of vit C increases.
Ascorbic acid-dependent mammalian enzymes
 Vitamin C Koenzim bagi 2 Kel Hidroksilase

Asam askorbat memiliki peranan khusus dlm hidroksilase yg

mengandung Cu dan hidroksilase yg mengandung Fe terkait α-
ketoglutarat.
Dopamin β-hidroksilase : enzim yg mengandung Cu yg terlibat dlm
sintesis katekolamin, norepinefrin, dari tirosin pd medula adrenal dan
sistem saraf pusat. Selama hidroksilasi, Cu+ dioksidasi mjd Cu2+,pro-ses
reduksi kembali mjd Cu+ memerlukan askorbat yg dioksidasi mjd
monodehidroaskorbat
Prolin dan lisin hidroksilase dibutuhkan untuk modifikasi paska sin-
tesis dr prokolagen mjd kolagen, dan prolin hidroksilase dibutuhkan
untuk pembentukan osteoklasin dan komponen C1q dr komplemen.
Kebutuhan Vit C

Among the stresses known to increase vit C

needs are infections, burns, extremely high or
low temperatures,intake of toxic heavy metals,
the chronic use of certain medications
(aspirin, barbiturates, oral contraceptives),
cigarette smoking.
 Vit C Deficiency

Two of the most notable signs of a vitamin C

deficiency reflect its role in maintaining the
integrity of blood vessels. The gums bleed
easily around the teeth, and capilla ries under
the skin break spontaneously, producing pin-
point hemorrhages.
When Vit C concentrations fall to about a fifth
of optimal level scurvy symtoms begin to
appear. Inadequate collagen synthesis
causes further hemorrhaging. The skin
becomes rough, brown, scaly, and dry.
 Vit C Toxicity

Side effects of vit C supplementation such as GI distress and diarrhea.

Those with kidney disease, a tendency toward gout, or a genetic abnor- mal-
ity that alters vitamin C’s breakdown to its excretion products are prone
to forming kidney stones if they take large doses of vitamin C.
Vitamin C supplements may adversely affect people with iron overload.
Vitamin C enhances iron absorption and releases iron from body stores; too
much free iron causes the kind or cellular damage typical of free ra- dicals.
These adverse consequences illustrate how vitamin C can act as a
prooxidant when quantities exceed the body’s needs.
High Doses Vitamin C??
Asupan vit C 100 mg/hari, kapasitas
tubuh untuk memetabolisme vit C
mengalami kejenuhan dan asupan
yg lebih tinggi akan diekskresi lewat
urin.
Vitamin C dpt mengurangi durasi
dan beratnya gejala common cold.
Mega-dose vitamin C in treatment of the
common cold: a randomised controlled trial

Doses of vitamin C in excess of 1 g

daily taken shortly after onset of a cold
did not reduce the duration or severity
of cold symptoms in healthy adult
volunteers when compared with a
vitamin C dose less than the mini-
mum recommended daily
intake (MJA Vol 175, 2001).
 Referensi

1. Rolfes SR, Pinna K, Whitney E. Understanding Normal and Clinical Nutrition

8th ed. USA : Wadsworth. 2009.
2. WHO & FAO. Vitamin and Mineral Requirements in Human Nutrition 2nd ed.
2004
3. Ball GFM. Vitamins Their Role in the Human Body. UK : Blackwell Publishing.
2004
4. Hemila H, Chalker E. Vitamin C for preventing and treating the common cold.
CochraneDatabaseSystRev. 2013.Jan 31(1):CD000980.
5. Quidel S, Gomez E, Soto GB, Ortigoza A. What Are the Effects of Vitamin C on
the Duration and Severity of the Common Cold? Medwave. 2018.18(6):e7261.
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