SUBJECT: BIOCHEMISTRY

TOPIC: WATER SOLUBLE VITAMINS

LECTURER: DR. CHONGLO-SY

DATE: FEBRUARY 2011

Vitamins (micronutrients) And if we cook the vegetables too long, we

 Classes
o Fat soluble vitamins (only 4 Vit A, D, E, K)
o Water soluble vitamins
Water soluble vitamins
*the toxicity of the water-soluble vitamins is less than that of
the fat-soluble vitamins because water soluble vitamins can
easily be excreted out through the urine. So toxicity is not
much of a problem, although sometimes, some people have
some manifestation of some sort of toxicity but not always.
lose some vitamins.
 Diverse physical properties
 Active only in coenzyme form
 Not used by the body as source of energy but will help
you get energy from the food that you eat
 Not for structural purposes
Function as coenzyme
 Carriers of chemical moieties (e.g. protons, electrons,
one-carbon, methyl, CO2, acetyl groups) in reactions
 Coenzyme: low molecular weight substance that
carries a characteristic group during the reaction

Again, in terms of TOXICITY Water-soluble vitamins

Fat soluble vit > water soluble vit  B-complex family

o B1
o B2
Importance: needed in growth, maintenance and o B3
reproduction o B5
o B6
Function: cofactors in enzymatic reactions o B12
o Biotin
*cofactors are ions which helps enzymes in a o Folic acid
o Lipoic acid
reaction
o Choline (not a vitamin; encountered in
lipidsphosphatidylcholine)
*coenzymes are low molecular weight organic
 Vitamin C
compound (but bigger than cofactors) which helps
enzyme in its action Biotin (Vitamin H)

without the vitamins in active form, the enzymes  Sources: Organ meat, egg yolk, nuts, legumes,
would not act chocolate, milk,
o Bacterial synthesis in the intestines
These vitamins are useless if not activated to their  Deficiency: dermatitis, hair loss (can also be observed
active coenzyme form in other vitamin deficiencies)
 Forms:
Generalities o Biocytin (active form)– biotin bound to protein
through its lysine residue (by an amide bond
 Required in the diet between C=O and ε-NH of lysine). *lysine – basic
o Most of the vitamins cannot be synthesized amino acid
by the body except some(example: Vitamin  Formed by linking the carboxylic group (COOH)
B [from aromatic amino acids]) of biotin with the ε amino (NH) group of lysine of
 Needed only in minute amounts the protein
 Organic in nature (low molecular weight organic  Active site: site in the molecule where the
substances) molecules carried by the vitamin will be
 Chemically varied attached
 It carries carbon dioxide (CO2) in carboxylation
 Dissolve in water
reactions
 Not stored
 Excess eliminated in urine
 Easily deactivated, destroyed or washed out (lost)
during storage and preparation
o We lose vitamin in the food we eat. Example
when we eat rice, we lose some Vitamin B1.

BIOCHEMISTRY: WATER SOLUBLE VITAMINS Page 1

 o Free biotin o Propionyl CoA carboxylase
 Propionyl CoA + Carbon dioxide
methylmalonyl CoA  succinyl CoA (enter
TCA cycle to be metabolized)
 Found in fat metabolism

 Substances that inhibit biocytin activity

o Avidin –Protein that binds biotin in a nondigestible
form (prevents biotin from being absorbed in the
gut). Avidin is present in raw seafood.

Biotin is absorbed in the gut in free form.

Once it enters the tissues then it can be
converted into biocytin by linking with a
protein with lysine

o Biotidinase -Enzyme that cleaves biocytin to biotin

& lysine o 3-Methylcrotonyl-CoA carboxylase
 Transport of biotin  found in branched chain amino acid
o Facilitated transport metabolism
o Passive diffusion
 Biotin dependent enzymes Vitamin C
o Acetyl CoA carboxylase
 Found in fat metabolism  Ascorbic acid
 Acetyl CoA + carbon dioxide  malonyl CoA +  Carbohydrate in origin (through the Uronic Acid
acetyl CoA  Fatty acid Pathway, ascorbic acid is derived from glucose in
o Pyruvate carboxylase some animals but not in man)
 Pyruvate + carbon dioxide  Oxaloacetate
 1st step in gluconeogenesis in mitochondria
 energy requiring step In man, uronic acid pathiway is utilized to produce
glucuronic acid (found in bilirubin). In addition, man
cannot synthesize ascorbic acid because it lacks the
pyruvate (salt) vs pyruvic acid (acid) : pyruvate is enzyme oxidase. This then prevents the conversion of
usually written because these compounds have pK uronic acid metabolites to Vitamin C.
lower than 7. At the normal body pH (pH 7.4=basic)

these compounds will be ionized.  COFACTOR in :

o collagen formation
Otherwise, if the environment is too acidic, pyruvate o hydroxylation of lysine and proline residue
will become pyruvic acid.  lysine (lysyl hydroxylase) hydroxylysine
 proline (prolyl hydroxylase)  hydroxyproline

hydroxyproline and hydroxylysine are products of

post translational processes. They are not derived
from the translation process.

 Glucose derivative
o D-glucose  D-gulose
 180° turn: glucose is inverted to become D-
gulose
o D-gulose  L-gulose
o L-gulose L-gulonic acid

BIOCHEMISTRY: WATER SOLUBLE VITAMINS Page 2

  One carbon (aldehyde group) of L-gulose is
oxidized making it L-gulonic acid (a sugar acid)
o L-gulonic acid  L-gulonolactone
o L-gulonolactone  ascorbic acid
 Catalyzed by the enzyme L-gulonolactone
oxidase
o L-ascorbate (active)  Dehydroascorbic acid
(inactive)
 Functions
o Carnitine synthesis
 Carnitine is important in the transport of acyl
CoA from cytosol in the mitochondria for
elongation of fatty acid
o Tyrosine metabolism
o Anti-oxidant
 Keep iron in reduced form (Fe2+)
 Fe3+  Fe2+
o Facilitates iron absorption
 Sources
o Broccoli, cabbage, spinach, turnips, collard greens
o Papaya, guava, orange, lemon, melon
 Properties
o a 6-carbon lactone
 lactone = ring + carbonyl group
o with 2,3-enediol structure
 double bond between C2 and C3
o dibasic acid
 pK1 : 4.1
 pK2 : 11.8
 strong reducing agent
 reduces ferric (Fe+3) to Ferrous (Fe+2)
iron is absorbed in ferrous form
 at pH 7, it has already donated one hydrogen
 Vit C is usually a monosodium ascorbate at
pH7
BIOCHEMISTRY: WATER SOLUBLE VITAMINS
Can man therefore metabolize L-xylose? No, it cannot be
metabolized so this is found in the urine together with the L-
threonic acid and oxalic acid
Metabolites of degredation of ingested ascorbic acid
 L-threonic acid
 Oxalic acid
 L-xylose
L-xylulose (ketose)  L-xylitol (at PPP)
Can man metabolize L-xylulose?
 Man can metabolize 5 carbon sugars like xylulose but
we cannot metabolize L-sugars
 L-xylulose  D-xylulose for metabolism
o Catalyzed by xylulose dehydrogenase
o if enzyme is absent, there will be
accumulation of L-xylulose in urine
o pentosuria
 loss of vitamin C
o during storage (through action of oxidases)
o exposure to oxygen
o during cooking: boiling
 Vitamin C Deficiency
o Decreased wound healing because collagen
formation will not be allowed without Vitamin C
o Scurvy
o Osteoporosis
Lipoic Acid
 6 – Thiocytic Acid
 6,8 DITHIO OCTANOIC ACID
o
o8-carbon
owith COOH
o6,8 dithio octanoic acid (oxidized): S-S
 function in oxidation reaction
o 6,8 disulfhydryl octanoic acid (reduced): SH
 function in reduction reaction
 Dietary sources
o dark green leafy vegetables e.g. spinach
o tissue rich in mitochondria e.g. heart and kidney
 coenzyme form
o lipoamide – bound to lysine (amide bond: εNH –
COOH)
 similar to biotin
o part of multienzyme complexes
Page 3
(refer to the figure above)  usually occurs as polyglutamate derivatives with 2 to 7
glutamic acid residues (or even up to 10 glutamic acid
Lipoic acid is part of the multienzyme complex of pyruvate residues attached to the folic acid)
dehydrogenase. CO2 is removed from pyruvate and 2 carbons  sources:
that are given to thiamine. This is another coenzyme, o dark green leafy vegetables
o meats , fish
thiamine to form acyl-thiamine. The acyl group is then given
o whole grains & cereals
to lipoic acid (S-S) and in the process your lipoic acid carries o legumes
the 2-carbon group forming acyl lipoic acid. Then the lipoic
acid gives the 2 carbon to coenzyme A (Vit B5). Coenzyme A
carries now acyl group forming acetyl coenzyme A and in the
process lipoic acid is converted into its reduced form (SH).
The reduced lipoic acid has to be converted to the oxidized
lipoic acid to become active this is done with the help of FAD
(Vit B2). FAD oxidizes the SH and the SH becomes S-S and
FAD carries the electrons forming FADH2. And the electrons
then are given to NAD. And NAD carries the electrons forming
NADH. In the process FADH2 becomes FAD. Now, NADH
carries electron to the electron transport chain.

 Function
o In oxidative decarboxylation of α-keto acids Conjugase enzymes would split the pteroyl Glutamic acid or
o Part of dihydrolipoyl transacetylase
the folic acid by splitting the CONH (amide bond). The
 Effect of arsenic poisoning
o Inhibits lipoic acid-requiring enzymes: conjugase actually removes the Glutamic acid portion of the
 Pyruvate dehydrogenase folic acid.
 multienzyme complex :
o 3enzyme
 pyruvate dehydrogenase
 dihydrolipoyl transacetylase
 dihydrolipoyl dehydrogenase
o 5 coenzyme
 thiamine pyrophosphate
 lipoic acid
 coenzyme A (Vit B5)
 FAD (Vit B2)
 NAD (Vit B3)
 Links glycolysis (anaerobic) to TCA (aerobic)
 Pyruvate acetyl CoA
o decarboxylation
 α-Ketoglutarate dehydrogenase (in TCA cycle)
 Function of lipoic acid is the same with that
in pyruvate dehydrogenase. Only the  active sites : N5 and/or N10
substrate and the product were altered.  where one carbon moiety is carried
 branched chain α-keto acid dehydrogenase
(found in the branched chain amino acids).
 The branched chain amino acids have the
same dehydrogenation reaction,
 1st step: oxidative decarboxylation
(catalyzed by the multienzyme complex)
 Branched chain aa: Leucine, Isoleucine,
Valine
o trivalent arsenite reacts with lipoic acid forming a
complex with the SH groups
conversion of DHF2 to THF4 (reduction reaction) catalyzed by
Lipoic acid acts on fatty acids, carbohydrates and lipids . dihydrofolic acid reductase

Folic Acid dihydrofolic acid reductase is important in nucleic acid

synthesis
 coenzyme form (active): tetrahydrofolic acid (THF4)
 function: coenzyme in one-carbon transfer reactions  site for inhibition of many drugs
(e.g. purine and pyrimidine synthesis, thymidylate
synthesis, etc.) hydrogen used is from NADPH provided by the pentose
 inactive form: dihydrofolic acid (DH2) phosphate pathway (PPP)

*Nowadays, expectant mothers are prescribed to take folic

acid to prevent neural tube defects of fetus  Multiple forms of folate
o pteroyl glutamate, folacin
 aka. Folacin
 simplest form: pteroyl-monoglutamic acid
o acid: pteroic acid

BIOCHEMISTRY: WATER SOLUBLE VITAMINS Page 4

 Thiamine or Vitamin B1

 Required for proper nerve transmission

 Thiamine is destroyed by thiaminase (found in raw
seafood)
 Coenzyme that will facilitate the breakdown of
carbohydrates
o Thiamine as part of the enzyme complexes,
thiamine deficiency may manifest with lack of
energy, always tired because there is no oxidation
 one carbon fragments
o –CH2 : Methylene of foodstuff
o –CHO : Formyl  Structure
o –CH= : Methinyl o Pyrimidine ring (Pteridine ring)
o –CH=NH : Formimino (formaldehyde + amino o Thiasol ring
group)

Fglu (formiminoglutamic acid) is found in the metabolism of

Histidine
If Fglu is found in the urine there must be a defiency in folic
acid thus there is a problem with histidine metabolism

o -CH3 : Methyl

Very often, the methyl group carried by vitamin B12 is derived

form folic acid. Sometimes, the folic acid deficiency can be
mistaken for vitamin B12 deficiency  Coenzyme form (active): Thiamine pyrophosphate (TPP)
 In the presence of TPP synthetase ATP, thiamine 
folic acid participates in the metabolism of nucleic acid TPP
and amino acid  Easily absobed in the gut as thiamine, then when it
reaches the tissues it will then be converted to TPP
 Reactions using THF4
o Synthesis of thymidylate  Coenzyme for:
o Pyruvate dehydrogenase
 Links glycolysis to TCA cycle

the methyl group is added to deoxyuridine

monophosphate to form thymidine monophosohate.
N5N10 methylene THF so the one carbon is carried and
this becomes DH2. But the one carbon has been donated
of dUMP forming the TMP. DH2 has to be converted back
to TH4 (active) by reduction of DH2 through NADPH (from
o α-ketoglutarate dehydrogenase
PPP).

Another reaction is the conversion of serine to glycine.

One carbon is removed form serine and donated to TH4 to
form glycine.

 Coenzyme in single carbon metabolism

o In Methionine and SAM synthesis
 Methyl group is given to homocysteine to
form methionine
o In catabolism of Histidine
o In serine and glycine methyl transferases
 Interconversion of serine and glycine
 Folic acid analogues (used in cancer therapy)
o Aminopterin – 4 amino folic acid (look alike of TH4)
o Methotrexate – 4 amino N10 methyl folic acid
(antineoplastic agent which interferes with the
synthesis of thymine)

BIOCHEMISTRY: WATER SOLUBLE VITAMINS Page 5

 o transketolase (involved in rearragement in the PPP) Vitamin B2 conversion to cofactors
 catalyzes the transfer of 2 carbons to the 5
carbons to form the 7 carbons
 this enzyme is being followed up to assess
the status of a person whether he is
suffering from B1 deficiency or not

o branched-chain keto-acid dehydrogenase (for val,

leu, ile)
 specific function
o decarboxylation of α keto acids in the
dehydrogenase reactions
o utilization of pentoses in HMP shunt (or PPP)
o carries acetyl carbon (2)
 sources (almost all foods are rich in B1)
o Ribitol: sugar alcohol
o whole and enriched grains
o Flavin: isoalloxazine
o meats o Riboflavin = ribitol + flavin
o eggs o FMN = riboflavin + phosphate
o potatoes, mik o FAD = FMN + adenine monophosphate
o legumes, nuts, seeds  Assesment of activity
 required daily allowance: 1 mg o Measurement of erythrocyte glutathione
o higher RDA with diet rich in carbohydrates reductase
 Vitamin B1 deficiency  Dietary sources
o Cow’s milk
o Termed BeriBeri in humans
o Liver
o Produces anorexia, weight loss, nausea, peripheral o Meat and dairy products
neuropathy and irritability o Grain and cereals
o Moderately severe o Legumes
 Seen in chronic alcoholics o Dark green vegetables (broccoli and spinach)
 Wernicke-Korsakoff syndrome  Vit B2 deficiency
o Common in people who are fond of o Angular cheilitis
o Glossitis
drinking alcohol with B1 deficiency
o Scaly dermatitis
o Pyruvic acid accumulates and is o Sore throat
converted to lactic acid
 Increase insolubility of uric Niacin or Vitamin B3
acid
o Severe  Nicotinic acid or nicotinamide
 Dry beriberi  Synthesized from tryptophan in small amount
 Wet beriberi  Coenzyme functions
o Mobile carrier in oxidation reduction reactions
Riboflavin or Vitamin B2 o Cellular respiration
 Coenzyme forms
 Coenzyme forms: flavin mononucleotide (FMN), Flavin o NAD and NADP [oxidized] (converted to NADH &
adenine dinucleotide (FAD) NADPH [reduced] respectively)
 Function: participates as electron carriers (2 electrons) in o NADPH functions in reductive biosythesis of fatty
redox reaction and cellular respiration acids and steroids (hydroxylation of
cycloperhydropenantrene ring)
 Nicotinamide carries hydride ions (one proton and 2
electron).

BIOCHEMISTRY: WATER SOLUBLE VITAMINS Page 6

NAD  Forms

Pyrydoxine Pyridoxamine Pyridoxal

(alcohol) (aldehyde)

Coenzyme Coenzyme form: Coenzyme form:

form: pyridoxamine pyridoxal phoshate
pyridoxine phoshate
phoshate

 Dietary sources: Whole grains, Cereals, Meat, Eggs,

nut and seed, fish, vegetables (carrots, beans, broccoli)
 Deficiency: similar to those of the other B vitamins:
 Dietary sources of Vit B3 nervousness, depression, chapped lips, glossitis
o Legumes
o Meat  Toxicity: Doses 1000 X RDA may produce difficulty
o Poultry in walking, & tingling sensations in the legs & soles of
o Fish the feet
o Peanuts  Coenzyme forms
o Milk o Pyridoxal phosphate
o Eggs o Pyridoxine phosphate
 Deficiency of B3
o Pyridoxamine phosphate
o Weakness, decreased appetite, skin erruptions,
dark scaly dermatitis
o Severe deficiency: PELLAGRA (diarrhea, dermatitis, *formed upon reaction with ATP
dementia)
Cobalamin (Vitamin B12)
Pantothenic acid (Vitamin B5)
 Extrinsic factor
 Coenzyme forms: deoxyadenosyl cobalamin, methyl
cobalamine

 Formed by combination of pantoic acid and B-alanine

 Coenzyme form: coenzyme A (found also in acyl carrier
protein, ACP)

 Vit B5 deficiencies are rare because of wide

distribution of pantothenic acid
 Function: coenzyme used for activation of compounds

Pyridoxine, pyridoxamine, pyridoxal (Vitamin B6)

o involved in transamination of amino acids

o coenzyme of glycogen phosphorylase and
heme synthesis

BIOCHEMISTRY: WATER SOLUBLE VITAMINS Page 7

  Functions
o Metabolism of propionyl CoA

o Methyl group transfer

 Sources: meat fish, dairy producs, oysters, shellfish

 Vitamin B12 function
o Mediated by receptor sites in the ileum
o Requires binding of a glycoprotein intrinsic
factor and cobalophilin

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