Vitamins (302 c) for third year Chemistry/Biochemistry students

•Water soluble vitamins by

Dr. Rasha F. Zahran Lecturer of Biochemistry

Faculty of Science

• Damietta University

Vitamin C, B1, B2 & B3

Water soluble vitamins

5. Vitamin B6 (Pyridoxine)

1. Vitamin B1 (Thiamine)

6. Vitamin B7 or Vitamin H

(Biotin)

2. Vitamin B2 (Riboflavin)

7. Vitamin B9 or Vitamin M

or (Folic acid)

3. Vitamin B3 (Niacin)

8. Vitamin B12

(Cyanocobalamin)

4. Vitamin B5 (Pantothenic

acid)

Vitamin B Group

Water Soluble Vitamins

Vitamin B Group

Vitamin B1 (Thiamine)

Vitamin B1

Natural Sources

Thiamine are found in many nuts, seeds, brown rice,

seafood, and whole-grain products (Grains are stripped of

the B vitamin content during processing).

Sunflower seeds are a particularly good source.

Legumes, milk, and beef liver.

Vitamin B1 (Thiamine)

The 1st water-soluble B-vitamin family to be discovered.

Since body reserve of thiamine is small (~30mg), a steady

dietary supply of it is important to avoid deficiency.

Because of its central role in energy production, most of

thiamine is located in the muscles.

Once thiamine absorbed, it is rapidly transformed into the

active form, thiamin pyrophosphate (TPP) which acts

as a coenzyme.

Pyrimidine

Ring

Methyl

Bridge Thiazole Ring

Thiamin or Aneurine

Daily Required amount and Sources

RDA (Recommended Dietary Allowance )is based on

the number of calories in diet:

Energy requirement

Adult male: 3000 k cal.

Female: 2100 k cal

Children : 1700-2000 k cal

Daily requirement increases with high carbohydrate

intake and for hard worker or athletes.

Vitamin B1 requirement

1.5 mg/day

1.1 mg/day

1mg/day

Stability of Thiamine

Stable in crystalline form but not so in solution.

Destroyed by prolonged heat, baking soda (with heating),

sulfite preservatives.

Unstable in aqueous solutions with pH > 5.0. At pH 8.0 or

above, thiamine turns yellow and is destroyed by a

complex series of irreversible reactions.

In strong alkaline solution with the presence of oxidizing

agents, e.g. potassium ferricyanide, thiamine is

converted to thiochrome, which is blue fluorescent

compound and is used for fluoremetric determination of

vitamin B1 in foods, pharmaceutical preparations, and

biological fluids.

Thiochrome

Functions of Vitamin B1 1. It act as co-enzyme (TPP) in carbohydrate metabolism

(for glycolysis and Kreb’s cycle enzymes: pyruvate

dehydrogenase and α-ketoglutarate dehydrogenase), which

enable conversion of glucose into biological energy

through oxidative decarboxylation reactions. This role is

important:

To provide energy to the brain.

To improve transmission of nerve impulses by

providing nerves with energy.

To increase the efficiency of the heart muscles.

For the formation of RBC’s.

2. It act as co-enzyme for transketolase which functions in:

The pentose phosphate pathway to synthesize

NADPH.

The pentose sugars: deoxyribose and ribose are

involved in nucleic acids biosynthesis.

Thiamine Antagonists

Oxythiamine is a competitive inhibitor (Amino group

in pyrimidine ring is replaced by hydroxyl group).

Neopyrithiamine (It prevents the phosphorilation of

hydroxy ethyl group that is essential for activity

of the vitamin B1).

Thiaminase (found in raw fish destroys vitamin B1).

Causes of Thiamine Deficiency

Malnutrition.

A diet high in thiaminase-rich foods (raw freshwater

fish, raw shellfish, ferns)

Foods having anti-thiamine factors (tea, coffee etc.).

Chronic consumption of alcohol

Diagnostic Testing for Vitamin B1 deficiency

A diagnosis test for B1 deficiency can be determined by

measuring transketolase levels of erythrocyte.

Diseases of Vitamin B1 deficiency

Beriberi is the deficiency disease caused by lack of thiamine

resulted from malnutrition, alcoholism or other causes.

There are two major types of beriberi:

A. Dry beriberi: affect the nervous system

B. Wet beriberi: affects the cardiovascular system

and ends by Wernicke-Korsakoff

syndrome which affect the nervous

system.

Wet Beri-beri Dry Beri-beri

Symptoms : Dyspnea

orthopnea

Increased heart rate, enlarged

heart, heart failure.

Swelling of the lower legs.

Wernicke–Korsakoff syndrome:

-Ophthalmoplegia (paralysis

of one or more extraocular

muscles which are responsible

for eye movements)

-Confusion

- Coma

- Death if untreated.

Symptoms: Difficulty in walking

Painful tender muscles

Loss of sensation in hands

and feet

Loss of muscle function or

paralysis of the lower legs

Mental confusion/speech

difficulties

Vomiting and anorexia.

Diseases of Vitamin B1 deficiency (BERI-BERI)

People at high risk of Vitamin B1 Deficiency

Heavy alcohol consumers (Alcohol reduces absorption of

thiamin and interferes with its conversion to TPP).

Much consumption of coffee and black tea depletes

thiamin stores in the body and hinder its absorption.

Patients having liver cirrhosis, malabsorption syndromes,

diabetes, kidney disease, or hypermetabolism.

The elderly peoples with poor nutritional status and

difficulties with absorption.

Folate deficiency impairs absorption of thiamin.

Infants who are breastfed by thiamin deficient-mothers

can rapidly develop life-threatening signs of

thiamin deficiency.

Use of Thiamine in prevention and Therapy

1. Nerve disorders: Supplemental thiamin may be

effective in inflammatory nerve disorders (such as

trigeminal neuralgia) and in diabetic neuropathy.

2. Central nervous system disorders: e.g. Alzheimer’s

disease, anxiety, and depression associated with

anxiety.

3. Heart failure: Particularly in the elderly chronic heart

failure that responds poorly to conventional

medical therapy.

4. Anemia: Thiamin deficiency produces an anemia

resembling that of folate or vitamin B12 deficiency

(with macrocytosis) that responds to thiamin.

5. Disease caused by heavy alcohol consumption.

Vitamin B1- Drug Interactions

Oral contraceptives, antibiotics, sulfa drugs, and certain

types of diuretics may lower thiamine levels in the

body.

Vitamin B1 may intensify the effects of neuromuscular

blockers that are used during some surgical

procedures.

B vitamins are best absorbed as a complex, and magnesium

also promotes the absorption of thiamine.

Toxicity

Thiamin is virtually nontoxic.

Doses > 200mg may cause drowsiness in some people.

Rare, but severe, allergic reactions may be happened with

injectable thiamin.

Vitamin B2 (Riboflavin)

Vitamin B2 (Riboflavin)

Riboflavin is defined chemically as 7,8-Dimethyl-

10-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]

benzo [g] pteridine-2,4-dione and is a

yellow to orange-yellow powder and soluble

in water.

It is the precursor of phosphorylated coenzymes:

FMN, FAD, and flavin coenzymes linked

covalently to specific tissue proteins, at the 8-

α methyl position of the isoalloxazine ring.

Riboflavin is stored mainly in liver, kidney and heart

as it is or as FAD (70- 90%) or FMN.

Flavin adenine dinucleotide (FAD)

Rib

ose

mo

iety

Isoalloxazine moiety

Riboflavin = Vitamin B2

Riboflavin phosphate

Natural Sources

Milk, cheese, egg white and liver. leafy green vegetables, almonds and mature soybeans

Yeast. Other sources: Added as food coloring Fortify some foods as baby foods, breakfast cereals,

sauces, processed cheese, fruit drinks and vitamin-enriched milk).

Required Daily Amount and Sources

RDA is an average of 1.5 mg/ day

Mushrooms Yoghurt Milk – Egg

Mature Soya beans Spinach Calf liver

Stability of Riboflavin

Riboflavin and its coenzymes are sensitive to alkali and

acid but in the presence of light or UV light.

Riboflavin is photodegraded to yield lumiflavin (7,8,10-

trimethylisoalloxazine) under alkaline conditions and

to lumichrome (7,8-dimethylalloxazine) under acidic

conditions, and these products are biologically

inactive .

Therefore, phototherapy of neonatal jaundice and of

certain skin disorders may promote systemic

riboflavin deficiency.

Functions of Vitamin B2 1. Energy production:

The active forms of riboflavin are the phosphorylated

coenzymes FMN and FAD which play central roles in about 150

oxidation-reductions reactions and are involved in:

Metabolism of carbohydrates, fat, and protein.

Production of adenosine triphosphate (ATP) through

cellular respiration in mitochondria.

Activation of vitamin B12, folate, vitamin B6 and the

conversion of tryptophan to niacin.

2. Antioxidant action:

Riboflavin is a cofactor of glutathione reductase. This

enzyme helps in recycle of oxidized glutathione, which

plays a key role in maintaining proper function and preventing

oxidative stress in human cells including erythrocytes.

Causes of Riboflavin Deficiency

Malnutrition.

Health conditions which affect intestinal absorption.

Increase of vitamin excretion from the body.

Diagnostic testing for vitamin B2 Deficiency

A positive diagnostic test of serum riboflavin is by

measuring glutathione reductase levels of

erythrocytes.

Symptoms of vitamin B2 deficiency (Ariboflavinosis)

Red, scaly, painful, and itchy patches on sensitive skin

(around nose, ears, mouth, labia majora (female), and the

scrotum (male).

Painful fissures and cracks form at the angles of the mouth

(angular stomatitis) and on the lips (cheilosis), usually

associated with bacterial and fungal infection. The tongue and

throat become purplish and painful.

Mouth ulcers

angular stomatitis Red, scaly, painful

skin Cheilosis Mouth ulcers

Redness, burning, excessive tearing of eye.

Anemia with decreased production of red blood cells.

Deficiency of riboflavin typically produces symptoms

of vitamin B6 and niacin deficiency.

Redness, burning,

tearing of eyes

Anemia Symptoms of niacin

deficiency

People at high risk of vitamin B2 deficiency

Children, and adolescent, athletes, as well as during pregnancy

and lactation (cases with a high-energy output) need

additional vitamin B2.

People under high stress

Diabetics may have low level of riboflavin as a result of

increased urinary excretion.

The elderly people (nutritional inadequacy and problems with

absorption)

Patients administering thyroid hormones, oral contraceptives,

phenothiazines, barbiturates, probenacid, and Tricyclic

antidepressant.

Assay of Vitamin B2

Lumiflavin method:

Riboflavin solution or biological sample

is irradiated in alkaline medium to

yielded a chloroform- soluble lumiflavin,

measured by fluoremetry.

VITAMIN B3

(NIACIN & NIACINAMIDE)

Vitamin B3 (Niacin & Niacinamide)

Two main forms of Vitamin B3 are found in foods:

nicotinic acid (niacin) and nicotinamide

(niacinamide).

Niacin can be partially satisfied by intake of

tryptophan, which is converted by the liver into

niacin.

60 mg of tryptophan can be converted into about 1mg

of niacin.

Dietary requirements for niacin are described in terms

of niacin equivalents (NEs):

1NE = 60mg of tryptophan = 1mg of niacin

RDA: 13- 20 mg/day

Natural Sources

• Tuna is one of the best sources of niacin.

• Most processed grain products are fortified with niacin.

• Cheese, milk are highest in Tryptophan and about half of the Tryptophan consumed is used to make niacin.

• Required Daily Amount: About 7 mg/ 1000 calories. 13- 20 mg/day.

•

Sources of Vitamin B3

Nicotinic acid or Niacin Nicotinamide or Niacinamide

Meat Fish Sheep liver Prawns Cow’s milk

Rice bran Groundnuts Chilgozas Turnip Beet greens

Yeast Bran

Pharmacokinetics of Vitamin B3

Absorption:

At low concentration by active transportation.

At high concentration by passive diffusion.

Transportation:

Both Nicotinic acid and Nicotinamide bind to plasma

proteins for transportation.

Biosynthesis:

The liver can synthesize Niacin from the essential

amino acid Tryptophan, but the synthesis is

extremely slow and requires vitamin B1, B2, and

B6 (60 mg of Tryptophan 1mg of niacin).

Bacteria in the gut may also perform the conversion

but are inefficient.

Functions of Vitamin B3

1. It acts as a co-enzyme in oxidation reduction reactions:

Catabolic Rxn: in form of NAD+/NADH

Anabolic Rxn: in form of NADP+/NADPH

Therefore, it is required for functions of >200 enzymes

dealing with the biosynthesis of several compounds

e.g. fatty acids, steroids and catabolism of fuel

molecules for energy.

2. DNA replication and repair:

It is vital for synthesis of DNA-bound nuclear proteins

(histones)

4. Blood sugar regulation:

It is a component of the glucose tolerance factor

(GTF), which together with insulin, helps to

control blood glucose.

5. Fat and cholesterol metabolism:

It lowers levels of total and LDL cholesterol in the

blood, while increasing levels of HDL

cholesterol (the healthy, protective form of

cholesterol).

3. Antioxidant functions:

It plays an important role in antioxidant systems,

particularly in the liver.

Vitamin B3 Deficiency Diseases

1. Milder deficiency of niacin (as well as tryptophan)

can cause:

Glossitis (inflammation of the tongue

leading to purplish discoloration)

Dermatitis around the mouth and rashes

Fatigue

Irritability

Poor appetite

Indigestion

Weight loss

Headache

Glossitis Dermatitis around

mouth Headache Fatigue Poor appetite Indigestion

2. Severe deficiency leads to Pellagra: Characterized by

Inflamed mouth (painful swollen tongue and

fissured lips) and GIT.

Diarrhea

Dermatitis in the exposed skin of hands, face, neck

(Casal’s necklace)

Dementia and mental disorders

Death.

It is very rare now, except in alcoholics, strict vegetarians,

and people with very poor nutrition (or niacin or tryptophan-

deficient food e.g corn).

Inflamed mouth Diarrhea Dermatitis of

exposed skin

Mental disorders Death.

People at high risk of vitamin B3 deficiency

People with very poor nutrition (or niacin or

tryptophan- deficient food e.g corn).

People with deficiencies in vitamin B6 or

riboflavin (conversion of tryptophan to

niacin is reduced niacin stores in the

body is reduced).

People with inflammatory bowel disease and

other digestive disorders malabsorption

of niacin.

Heavy alcohol consumption interferes with

absorption and metabolism of niacin.

People under high stress, chronic illnesses, liver

disease.

Uses in prevention and Therapy

Mental illness e.g. schizophrenia: Niacinamide can

be effective with traditional medical treatment.

Atherosclerosis and heart attack: Niacin in very

large doses (2-3 g/day):

(1) Lower total and LDL cholesterol and

raising HDL cholesterol.

(2) Dilates blood vessels lowers

blood pressure.

Arthritis: Niacin helps in treatment of osteoarthritis.

Diabetes: Niacinamide slow down the development

of nephropathy in diabetes and delay need for

insulin therapy in juvenile diabetes.

Protection against environmental toxins:

The antioxidant function of niacin

help protect liver against damage

from pesticides, chemicals, alcohol,

and drugs.

Headache: Niacin help in prevention of

headache.

Treatment of Pellagra.

Toxicity and side effects of vitamin B3

Large doses (500 mg) of niacin (but not niacinamide)

can cause dilation of capillaries tingling and

flushing of the skin.

Flushing of the skin is usually worse if nicotinic acid

is taken on an empty stomach, therefore it should

be taken just after meals.

Niacin in the form of niacinamide does not produce

these side effects.

At doses of > 2.5 g / day, it can produce hypotension,

dizziness, increased blood sugar and uric acid,

liver dysfunction, and increased risk of peptic

ulcer. These effects are gradually adopted and

decreased and are reversible on withdrawal of

nicotinic acid.

Vitamin B3 – Drug Interactions

Niacin with antihypertensive drugs severe

hypotension.

Extra niacin may be required in case of people taking

Isoniazid (antibiotics) (Inhibits biotransformation of

tryptophan to niacin), by women taking oral

contraceptives.

Bile acid sequesterants e.g. Cholestyramine and

cholestipol should be taken at a different time than

niacin (not niacinamide) otherwise they will

reduce its absorption.

Carbamazepine may cause toxicity with niacin.

The combination of niacin and statin is often used

to treat lipid triad (high LDL and TG, low

HDL) may cause myopathy (myopathy is a

muscular disease in which the muscle

fibers do not function, resulting in muscular

weakness).