NIACIN (B3)

2. NIACIN (B3)
Gandham.Rajeev
Email:gandhamrajeev33@gmail.com

3. Niacin
• Niacin or Nicotinic acid is also called as Pellagra
preventing factor
• Niacin is pyridine -3-carboxylic acid
• Nicotinamide is the amide form of nicotinic acid
• It is a white crystalline compound
• It is stable to heat & acid

4. Biosynthesis of niacin from tryptophan
• Dietary nicotinamide, niacin and tryptophan
contribute to the synthesis of the coenzymes NAD+
and NADP +
• 1 mg of niacin is formed from 60 mg of
tryptophan
• Phosphoribosyl pyrophosphate and ATP provides
ribose phosphate and AMP moiety for synthesis of
NAD+
• Glutamine donates amide group

5. • In the structure of coenzymes, nitrogen atom of
nicotinamide carries a positive charge due to
formation of an extra bond
• Hence coenzymes are NAD+ & NADP+
• Excretion:
• NAD+ & NADP+ is mostly excreted inurine as
N-methylnicotinamide

6. DIET
Nicotin amide Tryptophan
- C - O-
O
Niacin
Nicotinamide mononucleotide
Quinolinate
QPRT
Excreted in urine

7. Desamido - NAD
Nicotinamide mononucleotide
adenyl transferase
Glutamine
NAD+ Synthase
Glutamate
CH2
H
+
N
H
- C – NH2
O
O = P - O -
O = P - O -
I
O
I
O
I
I
O
I
CH2
H
N
N
NH2
I
N
N
OH
H
OH
HH
NAD+
NADP+
ATP ADP

8. Metabolism
• Absorption:
• It is absorbed from upper small intestine
• It occurs by simple diffusion
• Transport:
• It enters portal circulation, reaches general circulation
& enters all cells
• Storage:
• It is not stored in significant amounts in tissues
• In tissues, it gets converted into its coenzymes

9. Co-enzyme forms of niacin
• Co-enzyme forms of niacin are
• Nicotinamide adenine dinucloetide (NAD+)
• Nicotinamide adenine dinucloetide phosphate
(NADP+)

10. NAD dependent enzymes
• Carbohydrate metabolism:
• Glyceraldehyde 3P-Dehydrogenase:
• It catalyzes the conversion of Glyceraldehye 3P to 1,3
Bisphosphoglycerate
Glyceraldehyde - 3P
NAD
1,3 - Bisphosphoglycerate
Glyceraldehyde 3P-Dehydrogenase
NADH2

11. Lactate dehydrogenase
• It catalyzes the interconversion of lactate to pyruvate
• It occurs in anaerobic conditions ( pyruvate to lactate in
muscle & erythrocytes)
• Gluconeogenesis ( lactate to pyruvate in liver)
Pyruvate
NADH + H+
Lactate
Lactate Dehydrogenase
NAD+

12. PDH Complex
• Pyruvate dehydrogenase catalyzes the conversion of
pyruvate to acetyl CoA
• Dihydrolipoyl dehydrogenase utilizes NAD
• NAD is reduced to NADH + H+
Pyruvate
NAD
Acetyl CoA
PDH Complex
NADH + H+
CoASH
CO2

13. α- Ketoglutarate complex
• It catalyzes the oxidative decarboxylation of α-
ketoglutarate to succinyl CoA
• Dihydrolipoyl dehydrogenase component of α-
ketoglutarate dehydrogenase complex contains NAD
α- ketoglutarate
CoASH NAD+
Succinyl CoA
α- ketoglutarate
dehydrogenase complex
CO2 NADH + H+

14. Lipid metabolism
• β - Hydroxy acyl CoA dehydrogenase:
• It catalyzes the oxidation of β - Hydroxy acyl CoA to β -
Ketoacyl CoA
β - Hydroxy acyl CoA
NAD+
β - Ketoacyl CoA
β - Hydroxy acyl CoA
dehydrogenase
NADH + H+

15. β – Hydroxybutyrate dehydrogenase
• It catalyzes the inter conversion of acetoacetate to β –
Hydroxybutyrate
• Acetoacetate to β – Hydroxybutyrate in liver & β –
Hydroxybutyrate to acetoacetate extra hepatic tissues
Acetoacetate
NADH + H+
β – Hydroxybutyrate
β – Hydroxybutyrate
dehydrogenase
NAD+

16. Alcohol dehydrogenase
• It catalyzes the oxidation of alcohol to acetaldehyde
• NAD is reduced to NADH + H+
• Fatty liver & alcoholism:
• NADH + H+ generated during oxidation of alcohol
suppresses TCA cycle & diverts citrate for fatty acid
synthesis leading to increased synthesis of TAG
• Consumption of alcohol can lead to Fatty liver

17. Ethylalcohol (alcohol or ethanol)
NADH + H+
Acetaldehyde + CO2
Alcohol dehydrogenase
NAD+

18. • Branched chain α- ketoacid dehydrogenase:
• It catalyzes the oxidation of α- keto acid derived from
branched chain amino acids to corresponding acyl
CoA
Branched chain α- keto acid
CoASH NAD+
Corresponding acyl CoA
Branched chain α- ketoacid
dehydrogenase complex
CO2 NADH + H+

19. Tyramine dehydrogenase
• It catalyzes the conversion of tyramine to p-
Hydroxyphenyl acetate
Tyramine
NADH + H+
p-Hydroxyphenyl acetate
Tyramine dehydrogenase
NAD+

20. NAD+ or NADP+ dependent
• Glutamate dehydrogenase:
• It utilizes either NADP or NAD for the conversion of
glutamate to α- ketoglutarate & ammonia
Glutamate
NADH(P) H + H+
α- ketoglutarate
Glutamate dehydrogenase
NAD(P)+
NH3

21. Isocitrate dehydrogenase
• Cytosolic isocitrate dehydrogenase utilizes NADP &
mitochondrial isocitrate dehydrogenase utilizes NAD
• NADP+ dependent:
• Glucose - 6P dehydrogenase:
• It catalyzes the oxidation of glucose - 6P to 6P -
Glucanolactone
Glucose 6P
NADPH + H+
6P - Glucanolactone
Glucose - 6P
dehydrogenase
NADP+

22. Malic enzyme
• It catalyzes the conversion of malate to pyruvate &
CO2
• This reaction provides NADPH for fatty acid synthesis
and cholesterol biosynthesis
Malate
NADPH + H+
Pyruvate
Malic enzyme
NADP+
CO2

23. NADPH dependent
• β – Ketoacyl reductase:
• It is the one of the components of FAS complex
• It catalyzes the reduction of β – Ketoacyl molecule to β
– Hydroxyacyl molecule
β – Ketoacyl S-enzyme
NADPH + H+
β – Hydroxyacyl S-enzyme
Ketoacyl reductase
NADP+

24. HMG CoA reductase
• It catalyzes the reduction of HMG CoA to mevalonate
HMG CoA
2 NADPH + H+
Mevalonate
HMG CoA reductase
2 NADP+

25. Cholesterol 7α - hydroxylase
• It catalyzes the hydroxylation of cholesterol to 7α –
hydroxycholesterol
• It is rate limiting step in bile acid synthesis
Cholesterol
NADPH + H+
7α – hydroxycholesterol
Cholesterol 7α - hydroxylase
NADP+

26. Folate reductase
• It catalyzes the formation of tetrahydrofolate (FH4)
from folate
Folate
NADPH + H+
Dihydrofolate
Folate reductase
NADP+
NADPH + H+
Tetrahydrofolate
NADP+
Folate reductase

27. Phenylalanine hydroxylase
• It catalyzes the conversion of phenylalanine to tyrosine
Phenylalanine
NADPH + H+
Tyrosine
Phenylalanine hydroxylase
NADP+

28. • Dietary sources:
• Rich sources of niacin are liver, meat, fish, legumes,
whole grain cereals and dried yeast, tea & coffee
• Poor sources:
• Fruits, vegetables and corn
• Zein is major protein present in corn
• Zein is very low in tryptophan –provitamin of niacin

29. RDA
• Men - 15 – 20 mg/day
• Women - 14 mg/day
• Pregnant woman - 16 mg/day
• Lactation - 18 mg/day
• Deficiency:
• Causes:
• Inadequate intake
• Alcoholism

30. • Impaired absorption
• Antivitamins: Chronic administration of drugs such as
isoniazid (used in T.B) & 6-mercaptopurine (Leukemia)
• Pyridoxine deficiency:
• It associated with impaired conversion of tryptophan to
niacin due to decreased activity of PLP dependent
enzyme, kynureninase
• Hartnump disease:
• Associated with defective absorption of tryptophan

31. • Deficiency of niacin leads to the clinical condition
called pellagra
• Pellagra is caused by the deficiency of tryptophan &
niacin
• More common in women – because tryptophan
metabolism is inhibited by estrogen metabolits
• Symptoms:
• Dermatitis: In early stages, bright red erythema
occurs, in feet, ankles and face

32. • Increased pigmentation around the neck is known as
Casal’s necklace
• Dermatitis is precipitated by exposure to sunlight
• Diarrhea:
• Diarrhea may be mild or severe with blood & mucus
• Leads to weight loss
• Nausea & vomiting
• Dementia: Irritability, inability to concentrate & poor
memory

33. Pellegra. Niacin deficiency.
Dermatitis, diarrhea, dementia.

34. Same patient after niacin treatment.

36. Biochemical findings
• Decreased N- methylnicotinamide in urine
• Decreased plasma and erythrocyte concentration of NAD
and NADP
• Therapeutic uses of niacin:
• Niacin is used to (3-6 mg/day) treat hypercholesterolemia &
hypertriacylglycerolemia
• ( It inhibits flux of FA from adipose tissue, Acetyl CoA is
reduced
• It is also used to elevate plasma HDL levels
• It decreases LDL & VLDL levels
• Decreased activity of hormone sensitive lipase