Water soluble vitamins and its deficiencies

WATER SOLUBLE VITAMINS

Dr Greeshma
Dent of ¡DS mietn >

VITAMINS: CLASSIFICATION

O Vitamins are micronutrients that are required for
normal growth and maintainence of good health

Fat soluble vitamins
o vitaminA
o vitamin D
o Vitamin E

o vitamin K

Water soluble vitamins
- vitamin B complex
- vitamin C

VITAMINS

Synonyms

Chemistry

Coenzyme Forms

Functions

Nutritional Aspects: Sources
RDA

Deficiency Manifestations
Antivitamins

Coenzyme form Groups transferred

Thiamine

Thiamine(Bl) pyrophosphate(IPP) Aldehyde
Riboflavin(B2) FMN & FAD Hydrogen/electron
Niacin(B;) NAD & NADP Hydrogen/electron
Pantothenic acid Co enzyme A Acyl group(Fatty acid)
Pyridoxine(B,) Pyridoxal phosphate(PLP) Amino group, CO,
i
| Biotin Biotin CO,
Folic acid Tetrahydrofolate(THF) Werken til fem
methenyl
Cobalamine(B,,) Methyl cobalamine methyl

VITAMIN BI (THIAMINE)

Sources

= Vegetarian :Outer layer of cereals
unpolished (parboiled) rice

= Pulses, Oil seeds, nuts and yeast

= Animal sources: pork , liver, heart, kidney & milk

= RDA: 1 — 1.5 mg/ day

VITAMIN B, DEFICIENCY

7 Cerebral beriberi( Wernicke's- Korsakoff syndrome)
- In chronic alcoholics
- Due to: dietary insufficiency

impaired intestinal absorption

Characterised by:

encephalopathy, psychosis, apathy, loss of memory
and nystagmus(rhythmical to-and-fro motion of the
eyeballs)

THIAMINE DEFICIENCY (Beriberi)

Common earty manisfestations

may appear
(Poor prognosis;
vagus nerve
involved)

Wernicke"s
Syndrome

Opntnaimoptegia \
Confusion
Coma

=<
>Death

VITAMIN B,

Antivitamins:
= Tannin: excessive tea consumption

Pyrithiamine and oxythiamine (sulfa drugs-
antibiotics)

VITAMIN B, (RIBOFLAVIN)

= Riboflavin
» Warburg’s yellow enzyme

RIBOFLAVIN- coenzyme

u FMN: Flavin adenine mononucleotide
= FAD: Flavin adenine dinucleotide

Flavokinase FAD synthase
Riboflavin 7 FMN TN FAD
ATP ADP ATP PPi

Intestinal mucosal cell liver

RIBOFLAVIN

FAD dependant reactions:
=Oxidative decarboxyation:-
= PDH complex

pyruvate > Acetyl CoA + CO,
TPP, NAD, FAD. CoASH, Lipoic acid

=TCAcycle: succinate dehydrogenase

Succinate mw) Fumarate

VITAMIN B,: SOURCES

= Animal:
Liver Kidney Yeast
Egg Meat Fish
= Veg:
Cereals Pulses Milk

Fruits Green Leafy Vegetables

VITAMIN B,: DEFICIENCY

Symptoms involves skin and mucosal membranes

Cheilosis (inflamed lips)
Angular stomatitis
Glossitis

Seborrheic dermatitis
Corneal vascularization

Mes. reta

Antivitamins

T Applications/Uses:

- serve as research tools in animal experiments to
generate defined vitamin deficiency states with minimal
disturbance of other components of the diet.

- Some of these have clinical uses.
E.g.: Dicoumarol, as an anticoagulant .
Methotrexate, an anticancer agent

VITAMIN B,: NIACIN

= Pellagra preventing factor of Goldberger
= Pyridine derivative

= 2 forms: Nicotinic acid & Nicotinamide

nıacın

= 60 mg of tryptophan can synthesize Img of niacin
TPP Cu?+
Tryptophan === N-formyl kynurenine

FAD
3-OH-kynurenine <= Kynurenine

PLP. | Kynureninase

Fe?"

3-OH-anthranallic acid "a Quinolinic acid

_QPAT (rate-limiting step)
F si o = ji

NIACIN : COENZYME FORM

NAD* + He NADH + H +
=Cofactor for dehydrogenation reactions
=Enters electron transport chain — ATP synthesis

NADP + + H¿=BNADPH + H+
"Used for biosynthetic reactions

NIACIN : FUNCTION

NAD dependant reactions:
u Pyruvate dehydrogenase

Pyruvate =} Acetyl COA + co,
TPP, NAD, FAD. CoASH, Lipoic acid

= Glyceraldehyde-3-phosphate dehydogenase
= Lactate dehydrogenase

Lactate — nr PRES

NAD+ NADH+H+ |

GLYCOLYSIS
—

NAD DEPENDANT REACTIONS

= a-ketoglutarate dehydrogenase
= Isocitrate dehydrogenase TCA Cycle
= Malate dehydrogenase

= B hydroxy acyl CoA dehydrogenase ( B oxidation)
B-OH-acyl CoA mm} B-ketoacyl CoA

NADP DEPENDANT REACTIONS

= Glucose 6 phosphate dehydrogenase
Glucose-6-phosphate
NADP +

NADPH+H+
6-phosphogluconolactone

= Malic enzyme

NIACIN : SOURCES

Yeast Liver

Meat Fish

Legumes Cereals (outer coats)
Peanuts Sweet potato

- Niacin is formed in humans during catabolism of tryptophan.
It provides only 10% of the requirement. Remainder must
come from the diet

DEFICIENCY

NIACIN

NIACIN : ANTAGONISTS

O 3 Acetyl pyridine

(| Isoniazid

1.Explain the following aspects of thiamine.

a) Coenzyme form b) Biochemical functions/ metabolic
role and c) Deficiency

2.TPP as a coenzyme in three metabolic reactions of the
body.

3. Write coenzyme forms of and one reaction for each a)
Niacin b) Riboflavin

4. Deficiency manifestations of Niacin.

5. Explain the biochemical basis: a) Intake of polished

VITAMIN B,: PANTOTHENIC ACID-
chemistry

# Chick anti dermatitis factor

= Contains B- alanine

= Carrier of acyl groups

» Involved in metabolism of fat, proteins & carbohydrates

44

PANTOTHENIC ACID: active form

D Used in synthesizing two important acyl
carriers

1. Coenzyme A ( CoASH)

2. Acyl carrier protein( ACP of fatty acid
synthase complex)

PANTOTHENIC ACID: functions

Coenzyme A (CoA / CoA-SH)

Coenzyme (CoA) participates in several enzymatic
reactions of carbohydrate, lipid and amino acid
metabolism.

Important CoA derivatives:

Acetyl CoA, Succinyl CoA, HMG CoA, Malonyl CoA,
Palmityol CoA, Propionyl CoA

Acyl carrier protein

- Pantothenic acid is required for the synthesis of
phosphopantotheine of fatty acid synthase complex

- carry acyl groups in fatty acid synthesis

PANTOTHENIC ACID: Sources

Whole cereals

Legumes

Egg yolk

Liver

yeast

Also synthesized by bacterial flora in the intestine

RDA: 10mg/day

PANTOTHENIC ACID: DEFICIENCY

It is rare in humans ( due to widespread distribution
of the vitamin)

Gopalan’s Burning foot syndrome seen in
prisoners of war and during famine

manifested as:

-Painful burning sensations(Paresthesia) in feet
-Staggering gait

-impaired coordination & sleep disturbance

VITAMIN B,: PYRIDOXINE

Pyridoxal phosphate

Pyridoxal kinase
Pyridoxal =} Pyridoxal phosphate(PLP)
ATP ADP

[ ple FUNCTIONS

= Proteinmetabolism:
transamination

decarboxylation
transulfuration
deamination
= Lipid metabolism
sphingomyelin synthesis
= Carbohydrate metabolism
glycogenolysis
gluconeogenesis

PLP DEPENDANT REACTIONS

= Heme synthesis :
ALA synthase
Glycine + Succinyl CoA ——> o amino levulinic acid

= B, deficiency: anemia

PYRIDOXINE : SOURCES

= Egg, fish, meat milk, (rich sources)
= Beans, nuts, wheat, yeast, green leafy vegetables

=» RDA: 1-2mg/day

PYRIDOXINE: DEFICIENCY

Microcytic hypochromic anemia

PYRIDOXINE - ANTIVITAMINS

U) Isoniazid
(| Deoxypyridoxine
(| Methoxypyridoxine

VITAMIN B,: BIOTIN

= Sulfur containing vitamin
= Anti egg white injury factor/Vitamin H
= Synthesized by intestinal flora

= Coenzyme for carboxylases

BIOTIN

Imidazole ring
Biotin
Thiophene ring

coo”

valeric acid

BIOTIN DEPENDANT REACTIONS

= Pyruvate carboxylase
Biotin

Pyruvate + CO, ah Noe oxaloacetate
ATP DP+ Pi

= Substrate for TCA cycle

BIOTIN: SOURCES

widely distributed

Liver Yeast
Peanuts Soyabeans
Milk Egg yolk

Vegetables( tomato, carrot, cabbage, cucumber)
intestinal bacteria can synthesise biotin

BIOTIN: DEFICIENCY

= Prolonged use of antibiotics
= High consumption of raw eggs cause deficiency

Manifestations

= Dermatitis(erythematous rash: face)
= Atrophic glossitis
= Anorexia

BIOTIN ANTAGONIST

Avidin

= Present in egg white

= binds with biotin

= Prevent the absorption of biotin —biotin deficiency

Boiling of egg neutralize the inhibitory activity

BIOTIN - Antivitamins

Avidin
Desthiobiotin
Biotin sulphonic acid

1. Biochemical functions of Pantothenic acid.

2. Co-enzyme functions of Pyridoxal phosphate

3. Explain the biochemical basis:
a)B, deficiency can cause niacin deficiency.

b) Administration of pyridoxine along with isoniazide
in anti-tubercular treatment.

4. Name the anti-egg white injury factor, its source
and coenzyme function.

VITAMIN B,: FOUC ACID

Contains three components
-Pteridine ring
-Para amino benzoic acid (PABA)
-Glutamic acid (1-7 residues)

p-amino benzoic acid

Glutamate

GH-CH-CH,-COOH

i
H COOH

Pteridine nucleus Folie acid
ONC ac

FOUC ACID

E

Folate reducatse Folate reducatse
Folic acid ———> Dihydrofolate ===> THF

(N IN

NADPH+H* NADP* NADPH+H+ NADP*+

FOUC ACID: FUNCTIONS

2.Folic acid prevents neural tube defects that occur
during fetal development.

3.Folic acid is effective in lowering plasma
homocysteine concentration in patients with coronary
artery disease.

| FOUC ACID - One carbon metabolism

One-C Utilization

y y
(C2)

Tryptophan———+ N'°-formylTHF —+ Purines

Histidine
| THF
FIGLU ——>

N’, N'°-methenyl THF

N’, N’’methylene THF
Glycine — »| |

+ Glycine
o. Serine
>Thymidylate (AT MP)

Reductase

N°-methyl THF
THF

Methyl Cobalamin Cobalamin (Vit B12)

Homocysteine NZ yrettionine

FOUC ACID: FUNCTIONS

2.Folic acid prevents neural tube defects that occur
during fetal development.

3.Folic acid is effective in lowering plasma
homocysteine concentration in patients with coronary
artery disease.

FOUC ACID: SOURCES

Sources: abundant in green leafy vegetables(spinach,
cauliflower)

Yeast, liver, egg, vegetables, cereals, pulses and
oil seeds, Beans, peas

RDA: 200ug/day

Causes of Folate deficiency

Insufficient dietary intake
malabsorption
Increased demand-
pregnancy and lactation

Administration of
antifolate drugs

FOUC ACID: MANIFESTATION

Megaloblastic anemia
Homocysteinuria

Neural tube defects

GIT manifestations: Vomiting, Diarrhea, Abdominal
pain

Normocytes

Megaloblasts(folic acid,
B,, deficiency)

NEURAL TUBE DEFECTS

= In babies of pregnant women with folate deficiency
= Congenital malformations of spine (spina bifida)

Normal Anencephaly

FIGLU EXCRETION TEST

to assess folate deficiency

y

FIGLU (formimino glutamic acid)
ls Wale

FOUC ACID: ANTIVITAMINS

7 Sulfonamides- + synthesis of PABA in bacteria —
used as antibiotic

| Methotrexate- # folate reductase —|DNA synthesis
& mitosis— Anticancer Rx- leukemia

VITAMIN B,,: COBALAMIN

1.Methyl cobalamin(major form present in blood)

2. Deoxy adenosylcobalamin ( storage form)

COBALAMIN: ABSORPTION

= Requires the mediation of intrinsic factor(IF) secreted by
gastric parietal cells.

= IF-B,, complex binds to specific receptors on the intestinal
mucosal cells & internalized — B,, is converted to
methylcobalamin

= Transported as Transcobalamin-2
= If excess is converted 5’ deoxy

adenosyl cobalamin and stored
= Sufficient for 2 - 3 years

COBALAMIN: STORAGE

7 Unlike other water soluble vitamins, vitamin B,, is
stored in the liver and other tissues

7 Whole liver contains about 2mg of B,,, which Is
sufficient for 2-3 years.

COBALAMIN: FUNCTIONS

2. Reactions requiring deoxyadenosylcobalamin as
coenzyme

Methyl malonyl CoA isomerase
Methyl malonyl CA io, Succinyl CoA

3. Required for myelin sheath formation and proper
functioning of nervous system

COBALAMIN: SOURCES

= Only animal source _
Liver
Meat
Fish

A Egg

Curd (lactobacillus)

e RDA: 1-2ug/day

COBALAMIN: DEFICEIENCY CAUSES

= Lack of IF - common cause- Auto antibodies against
parietal cells (Pernicious anemia)

= Malabsorption - Gastrectomy, lleal resection

Prolonged antibiotic therapy

= Reduced intake- elderly people, Pregnancy

COBALAMIN: MANIFESTATIONS

| Pernicious anemia associated with nerve
degeneration and paralysis

1.Describe the coenzyme forms and functions of folic
acid.

2.Name two folate antagonists and their therapeutic
use.

3. FIGLU excretion test

4. Explain the biochemical basis:

a) Viamint B,, deficiency may lead to megaloblastic
anemia.

b) B;, deficiency can cause methyl malonyl aciduria.

c) Surgical removal of stomach causes pernicious
anemia.

VITAMIN C (ascorbic acid)

- The structure of ascorbic acid closely resembles
that of a hexose.

- Itis a strong reducing agent. The reducing property
of vitamin C depends on the double bonded carbons
(enediol).

- L-ascorbic acid undergoes oxidation to form
dehydroascorbic acid and this reaction is reversible.

I VITAMIN C : FUNCTIONS

8.Reduces cataract formation

9. Role in iron absorption
Vitamin C facilitates by reducing Fe**to Fe** form

10. Regeneration of hemoglobin

MetHb c= Hb

11. Immunological function
hances synthesis of immunoglobulins( antibodies)

VITAMIN C : SOURCES

Gooseberry(amla), Citrus fruits, Cabbage-type vegetables -

Broccoli

Strawberries, Tomatoes, Papayas, Mangoes

Milk is a poor source

RDA 75mg/day

Citrus fruits, green peppers, strawberries,
tomatoes, broccoli and sweet and white
potatoes are all excellent sources

of vitamin C

ch

VITAMIN C : DEFICIENCY

1] Cause:
- Intake of foods devoid of fresh fruits and vegetables

O Manifestations:

Scurvy

Due to
1. Formation of defective collagen
2. Low absorption of iron

VITAMIN C DEFICIENCY - SCURVY

Bone: frequent fractures
= Infections &Delayed wound healing

Low iron absorption results in
Microcytic hypochromic anemia

Antivitamins

T Applications/Uses:

- serve as research tools in animal experiments to
generate defined vitamin deficiency states with minimal
disturbance of other components of the diet.

- Some of these have clinical uses.
E.g.: Dicoumarol, as an anticoagulant .
Methotrexate, an anticancer agent

1. Functions of Ascorbic acid

2. Explain the biochemical basis:

a) Vitamin C deficiency may result in bleeding gums,
frequent fractures and delayed wound healing.

b) Vitamin C facilitates iron absorption in the intestines.

3. What are anitivitamins? Give their significance with
two examples.

Y Thank Y
‘ “i fou ¢ 7

Water soluble vitamins and its deficiencies

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Water soluble vitamins and its deficiencies

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