For Paramedicals, Allied Healthy Sciences and medical students

1. Have a great day to all
“More you want to achieve?
More you have to work for it’’ By
Dr. Santhosh Kumar N
Associate Professor of Biochemistry
Vitamin - B3
/ NIACIN / NICOTINIC ACID /
Pellagra preventive factor

2. Case report

3. • Niacin synthesized by essential amino acid Tryptophan
• Monocarboxylic acid derivative of Pyridine
• Niacin amide is acid amide form

4. SOURCES
– Dried yeast,
– Peanut,
– Whole cereals,
– Legumes
– Liver,
– Meat and fish.

5. RDA
– Adults : 15 to 20 mg/day
– During lactation : 25 mg /day
• Tryptophan  NAD+
• 60 mg of try =1mg of niacin =1mg niacin
equivalents (NE)

6. NIACIN
ppi
NADP+
NAD+
TRYPTOPHAN
Nicotinate Mononucleotide
PRPP
ATP
PPi
• Nicotinamide Adenine Dinucleotide (NAD+)
• Nicotinamide Adenine Dinucleotide Phosphate (NADP+)
Coenzyme of Niacin

7. AH2
:H- H+
OXIDIZED FORM REDUCED FORM Ionized
+ e-
Reduction process

8. NAD+ dependent Enzymes
Carbohydrate metabolism:
Glyceraldehydes 3-P-DH Gly 3-p → 1,3-bisphosphoglycerate
Lactate dehydrogenase Pyruvate → Lactate
Pyruvate dehydrogenase Pyruvate → Acetyl coA
Alcohol dehydrogenase Alcohol → Acetaldehyde
glutamate dehydrogenase Glutamate → α-ketoglutarate
Biochemical functions
• Its coenzyme mainly involved in oxidation reduction reactions

9. NADPH generated reaction
Glucose-6-phosphate dehydrogenase :
Glu-6-phosphate → 6-phosphogluconolactone
6-phosphogluconate dehydrogenase:
6-phosphogluconate →3-keto-6-phosphogluconate
Malic enzyme : Malate → Pyruvate

10. NADPH Utilizing Reactions
 HMG-CoA reductase: HMG-CoA → mevalonate
 Methemoglobin to hemoglobin
 Folate reductase : Folate → dihydrofolate → tetrahydrofolate
 Phenylalanine hydroxylase : Phenylalanine → tyrosine

11. Deficiency Manifestations of Niacin
PELLAGRA (means rough skin)
• Caused by deficiency of tryptophan & Niacin
• Mostly seen among people whose staple diet is corn or maize (low
content of Tryptophan)
• Seen more in women- Try metabolism inhibited by estrogen
metabolites

12. • Symptoms are commonly referred to as 3Ds
1. Dermatitis (skin lesions especially in the feet,
ankles and face).
2. Diarrhea (with blood & mucus)-weight loss
3. Dementia (irritability, inability to concentrate and
poor memory. Ataxia & spasticity )
Increased pigmentation around
the neck - Casal’s necklace.
Bright red erythema
Nails has irregular surface.
Ataxia: impaired balance or coordination , Spasticity: abnormal increase in muscle tone or stiffness of muscle

13. Causes for Niacin Deficiency
Dietary deficiency of tryptophan:
– Staple diet of maize (low Try) and sorghum (high quantities of leucine).
– It inhibits the quinolinate phosphoribosyl transferase (QPRT) &
• so niacin cannot be converted to NAD+ (Leucine pellagra).
Defect in synthesis:
– Kynureninase (PLP dependent enzyme) involved formation of Niacin,
• So, conversion of tryptophan to niacin is not possible in Pyridoxal deficiency.

14. • Isoniazid (INH):
– Antituberculous drug, which inhibits PLP formation.
• Hartnup’s disease:
– Tryptophan absorption from intestine is defective.
• Carcinoid syndrome:
– Tumor utilizes more tryptophan for synthesis of serotonin; so tryptophan is
unavailable

15. Therapeutic uses of Niacin
• Slow/ reverse progression of atherosclerosis with diet and exercise
• Nicotinic acid reduces serum cholesterol level.
• Decreases triglycerides synthesis in liver
• Inhibits lipolysis in adipose tissue & decreases the circulatory free fatty acids

16. Toxic effects
• Flushing of skin
• Itching
• Nausea
• Excessive sweating
• Impaired glucose tolerance
• Anti vitamins: Pyridine-3-sulfonic acid

17. Pyridoxine / B6

18. • Consists of 3 different closely related pyridine derivatives.
– Pyridoxine (alcohol)
– Pyridoxamine (amine)
– Pyridoxal (aldehyde)
– Pyridoxal phosphate (PLP) is the active form of Vitamin B6

19. sources
• Egg yolk
• Fish
• Milk
• Meat
• Wheat
• Cabbage
• Potatoes

20. RDA
• Adults : 1 to 2 mg / day
• Pregnancy & lactation : 2.5 mg / day
Toxicity of Vitamin B6
• Doses over 100 mg may lead to sensory neuropathy.

21. Biochemical functions
Transamination :
Alanine + α-keto glutarate Pyruvate + Glutamic acid
SGPT (ALT)
Aspartate + α-keto glutarate Oxaloacetate + Glutamic acid
SGOT (AST)
PLP
PLP

22. Decarboxylation
Amino acids undergo decarboxylation to form the respective amines :
Histidine Histamine
Histidine decarboxylase
-CO2
5-OH-Tryptophan Serotonin
5-OH-Tryptophan decarboxylase
-CO2
Glutamate GABA
Glutamate decarboxylase
-CO2

23. • Heme Synthesis
• Metabolism of Tryptophan
Glycine + Succinyl CoA Aminolevulinic acid (ALA)  Heme
ALA synthase
PLP
Tryptophan    3-OH-kynurenine 3-OH-anthranilic acid →→→ Niacin
PLP
Kynureninase

24. PLP functions
• Synthesis of sphingolipids and formation of myelin
• Absorption of amino acids from the intestine
• Formation of coenzyme A from pantothenic acid
• Prevent urinary stone formation

25. Deficiency manifestations of B6
Hematological In adults, hypochromic microcytic anemia (inhibition of heme biosynthesis).
Neurological In children, convulsions due to decreased formation of GABA.
Demyelination of nerves & consequent peripheral neuritis (defect in the
synthesis of sphingolipids).
Tingling sensation in the legs & limbs,
Irritability & seizures
Dermatological Niacin deficiency - pellagra. irregular indentations in nails.
Other metabolic
disorders
Xanthurenic aciduria & homocystinuria

26. antivitamin
– Isoniazid (Isonicotinic acid hydrazide, INH)
– Pencillamine
– Cycloserine

27. Believe In Yourself
Because
all power is within you;
You can do anything and everything