Dr. Ngadikun, M.Biomed.

Department of Biochemistry,
Faculty of Medicine,Universitas Gadjah Mada.
 Outline
I. INTRODUCTION
II. DEFINITION
III. ENERGYRELEASING WATER-
SOLUBLE VITAMINS
IV. HEMATOPOIETIC WATER-
SOLUBLE VITAMINS
V. OTHER WATER-SOLUBLE
VITAMINS
 INTRODUCTION
Water-soluble vitamins differ from fat-soluble vitamins
in several important aspects:
 Most are readily excreted once their concentration
surpasses the renal threshold  toxicities are rare.
 Deficiencies occur relatively quickly on an
inadequate diet.
 Their metabolic stores are labile and depletion can
often occur in a matter of weeks or months.
 Water-soluble vitamins are coenzymes for many
common biochemical reactions
The water-soluble B vitamins supply important
components of numerous coenzymes.
 As its pyrophosphate, thiamin participates in
decarboxylation of α-keto acids and
 Nicotinamide and riboflavin are components of
the redox coenzymes NAD and NADP and FMN
and FAD, respectively.
 Pantothenic acid is a component of the acyl
group carrier coenzyme A.
 folic acid and cobamide coenzymes function in
one-carbon metabolism.
Vitamin C Is the Coenzyme for hydroxylases
 DEFINITION
Definition: vita = life
amine = containing nitrogen (first vitamin
discovered contained nitrogen)

Vitamin: organic essential nutrients required in tiny

amounts to perform specific functions that
promote growth, reproduction and
maintenance of health and life

- do not yield energy when broken down they

assist in energy yielding pathways of
carbohydrate, lipid and protein metabolism
1. EnergyReleasing Water-soluble Vitamins
a. Thiamine

Thiamine  coenzyme thiamine pyrophosphate (TPP)

 pyruvate DH in carbohydrate metabolism;

 -ketoglutarate DH in the citric acid cycle; and
 transketolase, in the pentose phosphate pathway.
b. Riboflavin
 a Central Role in Energyyielding Metabolism: energy production
in cellular respiration.
 component of FAD and FMN.
Riboflavin: precursor of the coenzymes FAD and FMN
(redox reactions):
FMN: ATP-dependent phosphorylation of riboflavin,
FAD is synthesized by further reaction of FMN with ATP.
The main dietary sources of riboflavin: milk, meat, eggs,
and cereal products.
The isoalloxazine ring is the core structure of the different flavin molecules. It is
yellow in color and the word "flavin" is derived from the latin word for yellow, flavus.
 Flavin coenzymes can exists in three different redox states, and each state has a
different color (the reduced form is colorless)
Flavin molecules can participate in both one- and two- electron transfer reactions
Flavin Coenzymes: Electron Carriers in Oxidoreduction
Reactions:

 the
mitochondrial
respiratory
chain,
 key enzymes in
fatty acid and
amino acid
oxidation, and
 the citric acid
cycle.
c. Pyridoxine
Pyridoxine (Vitamin B6) Forms the Coenzyme Pyridoxal Phosphate

Six compounds have

vitamin B6 activity:
pyridoxine, pyridoxal,
pyridoxamine, and their
5′-phosphates.
The active coenzyme:
pyridoxal 5′-phosphate.
± 80% of the body’s total
vitamin B6 is present as
pyridoxal phosphate in
muscle, mostly
associated with glycogen
phosphorylase.
Vitamin B6 Has Several Roles in Metabolism
Pyridoxal phosphate:
 coenzyme for many enzymes involved in amino acid
metabolism (transamination and decarboxylation) for
energy production.
 cofactor of glycogen phosphorylase.
 the symptoms of severe B6 deficiency are similar to
those of the other energyreleasing vitamins.
 important in steroid hormone action (removes the
hormone-receptor complex from DNA binding, terminating
the action of the hormones).
 required for synthesis of
 the neurotransmitters serotonin and norepinephrine
 the sphingolipids necessary for myelin formation.
 the synthesis of aminolevulinic acid, a precursor of
heme.
Important metabolic roles of pyridoxal phosphate.
Reactions requiring pyridoxal phosphate are indicated with red arrows
d. Niacin
Niacin Is Not Strictly A Vitamin.
it can be synthesized in the body from tryptophan.
nicotinic acid and nicotinamide: biologic activity of niacin;
its metabolic function is as the nicotinamide ring of the coenzymes
NAD and NADP in oxidation-reduction reactions
 NAD Is the Source of ADP-Ribose
for the ADP-ribosylation of proteins and polyADP-ribosylation
of nucleoproteins involved in the DNA repair mechanism.

Poly (ADP-ribosa) polimerase (PARP)

Poly(ADP-ribose) glycohydrolase (PARG)
e. Pantothenic acid
Pantothenic acid: a component of coenzyme A and the
phosphopantetheine moiety of fatty acid synthase and thus is
required for the metabolism of all fat, protein, and carbohydrate
via the citric acid cycle.

Phosphopantetheine. Both acyl carrier protein and CoA include phosphopantetheine as

their reactive units.
f. Biotin
Biotin: prosthetic group for carboxylation reactions:
 pyruvate carboxylase (needed for synthesis of oxaloacetate for
gluconeogenesis and replenishment of the citric acid cycle),
 acetylCoA carboxylase (fatty acid biosynthesis), and

The reactive intermediate is 1-Ncarboxybiocytin, formed from

bicarbonate in an ATPdependent reaction.
2. Hematopoietic Water-soluble Vitamins
a. Folic Acid
The active form of folic acid is
tetrahydrofolate.

Tetrahydrofolate can carry one-

carbon fragments attached to
 N-5 (formyl, formimino, or
methyl groups),
 N-10 (formyl group), or
 bridging N-5 to N-10
(methylene or methenyl
groups).

5-Formyl-tetrahydrofolate is more
stable than folate
Various one carbon tetrahydrofolate derivatives are used in
biosynthetic reactions.

Metabolic roles of folic acid and vitamin B12 in one carbon metabolism.
The metabolic interconversions of folic acid and its derivatives are indicated with black
arrows. Pathways relying exclusively on folate are shown with red arrows. The important
B12dependent reaction converting N5methyl H4folate back to H4folate is shown with a
blue arrow.
b. Vitamin B12
Vitamin B12 Contains Cobalt in a Tetrapyrrole Ring

The term “vitamin B12”

is used as a generic
descriptor for the
cobalamins
—those corrinoids
(cobalt containing
compounds possessing
the corrin ring)
having the biologic
activity of the vitamin.
Absorption of Vit B12 Vit B12 bound to Intrinsic factor
(IF) by parietal cells of gastric
mucosa.
Gastric acid and pepsin: release
the vit from protein binding in food
 available to bind to cobalophilin
(binding protein secreted in the
saliva)
In the duodenum, cobalophilin is
hydrolyzed, releasing the vit for
binding to IF.
Pancreatic insufficiency: vit B12
deficiency (excretion of
cobalophilin-bound vit B12).
Vit B12: absorbed via receptors
bind IF-vit B12 complex but not
free IF or free vit.
Vitamin B12 is widespread in foods of animal origin,
especially meats.

Liver stores up to a 6-year supply of vitamin B12.

 deficiencies of B12 are extremely rare:

 older people due to insufficient production of IF
or HCl in the stomach.
 patients with severe malabsorption diseases
and
 longterm vegetarians.
Vitamin B12 Deficiency Causes Functional Folate Deficiency
a methyl donor, S-adenosylmethionine forms homocysteine, may be
remethylated by methyltetrahydrofolate catalyzed by methionine
synthase, a vitamin B12-dependent enzyme

reduction of methylene-H4folate to methyl-H4 is irreversible, and

since the major source of H4 for tissues is methyl-H4, the role of
methionine synthase is vital and provides a link between the functions
of folate and vitamin B12.
Impairment of methionine synthase in B12 deficiency results in the
accumulation of methyl-tetrahydrofolate
 3. Other Water-soluble Vitamins
Ascorbic acid

 the Coenzyme for Two Groups of Hydroxylases

 copper-containing hydroxylases and
 -ketoglutarate-linked iron-containing hydroxylases.
It also increases the activity of a number of other
enzymes in vitro, though this is a nonspecific reducing
action.

 a reducing agent, which appear to be nonenzymatic.

For example: in absorption of iron by reducing it to the
ferrous state in the stomach.
 stimulation of immune system, anti-oxidant for
scavenging of reactive free-radicals
A number of iron-containing, ascorbate-requiring hydroxylases share
a common reaction mechanism in which hydroxylation of the
substrate is linked to decarboxylation of -ketoglutarate.
Proline and lysine hydroxylases are required for the postsynthetic
modification of procollagen to collagen,

Hydroxylation of lysine and proline in protocollagen

Without these post-translational modifications the triple
helix of collagen is unstable and connective tissue loses its
integrity.
important for maintenance of normal connective tissue.
bone formation (bone tissue has an organic matrix
containing collagen).

Ascorbic acid deficiency:

 capillary fragility (collagen: component of the ground
substance surrounding capillary walls).
 osteoporosis (inability to maintain the collagenous
organic matrix of the bone, followed by
demineralization).
 scurvy (skin changes, fragility of blood capillaries, gum
decay, tooth loss).
 REFERENCE
Devlin TM. 1997. Textbook of Biochemistry with Clinical
Correlations. 4th Ed. John Wiley & Sons Inc. New
York.
Murray RK, Bender DA, Botham KM, Kennelly PJ,
Rodwell VW, Weil PA. 2009. Harper’s Illustrated
Biochemistry 28th Ed. McGraw Hill Companies Inc.,
USA.