DR. P. HAVILAH .M.DASSOCIATE PROFESSORDEPT OF BIOCHEMISTRY

SANTHIRAM MEDICAL COLLEGE.

NIACIN ( VIT B3)

NIACIN

Synonyms:Nicotinic acid, P-P factor, Pellagra

preventing factor of gold bergerChemistry:

Pyridine 3 – carboxylic acid

NIACIN NIACINAMIDE

COENZYMES

Active forms:NAD+ nicotinamide adenine di nucleotideNADP+ nicotinamide adenine di nucleotide

phosphate Reduced forms:

Dihydro – nicotinamide adenine dinucleotide (NADH)

Dihydro – nicotinamide adenine dinucleotide phosphate (NADPH)

NAD+

Niacinamide +ribose-p + AMPNitrogen atom of niacinamide contains one

positive charge

2 Molecule of D-ribose1Molecule of nicotinamide2. Molecule of Phosphoric

acid 1. Molecule of adenine

REDUCED NADH+H+

NAD+ accepts one hydrogen atom during reduction. The other Hydrogen is ionised and only e- is accepted which nullifies +ve charges

2H H + H + + Ie-

NADP+

OII

0-P-OO

One more phosphoric acid is

attached to ribose of AMP

NAD+ - reqd for ADP –ribosylation of proteins

In DNA – repair

NADH enters ETC and releases 3 ATP

NADPH used for reductive biosynthesis

BIOSYNTHESIS

syn From Aromatic A.A TRYPTOPHAN.

60 mg of Tryptophan can give rise to 1mg of Niacin

Pyridoxal – P acts as coenzyme in synthesis

QPRT -rate limiting step

Diet

Nicotinamide Nicotinate deaminase

PRPP Pi PP1

Quinolate PRPP NMN QPRT

Co2 ATP LEUCINE AMP+ppi

3-OH anthranilate Desamido NAD+ATP Glutamine

PLP AMP GlutamateTryptophan (Diet) NAD+

METABOLIC ROLE

NAD+ dependent Enzymes

1. LDH (lactate Pyruvate)2. GAL3DH (GAL3P 1, 3 BPG)3. PDH (Pyruvate Acetyl coA)4. α- KDH (α KGA SuccinylcoA)5. ICD, (ICD oxalosuccinate) 6. MDH (malate OAA)

Lipid metabolism7.β-hydroxy acylcoA dehydrogenase(. β

oxidation)8. . β -hydroxy butyrate (ketolysis)Protein metabolism9. Glutamate dehydrogenase10. Glycine cleavage11.Ketoacid dehydrogenase

NADPH Generating reactions:

1. G6PD in HMP shunt ( G6P 6phosphogluono lactone)

2. 6 –Phospho gluconate dehydrogenase 3 – Keto 6- Phospho gluconate

3. Malic enzyme (Malate Pyruvate)4. Cytoplasmic iso citrate dehydrogenase

(ICD)5. Glutathione reductase.

NADPH utilising reactions:

1. β- Keto acyl ACP β-OH acyl ACP2. α, β unsat ACP acyl ACP3. HMG coA Mevalonate4. Met Hb Hb5. Folate Dihydrofolate

Tetra hydrofolate6. Phenyl alanine Tyrosine7. Cytp450 - xenobiotics

Both NAD+ / NADP+ requiring enzyme

1. Glutamate dehydrogenase ( Glutamate αKGA

+ NH3) 2. ICD ( ISO citrate Oxalosuccinate3. Retinine reductase

Dietary sources:Animal : Liver, Kidney, Meat, FishVegetables: Legumes (Peas, beans, lentils),

nuts coffee, Tea

Recommended daily allowance: Adults: - 20 mg / day Pregnancy - 20 + 2 mg / day Lactation - 20 + 5 mg / dayMetabolism:Absorption: in small intestineBlood levels - 0.2 – 0.9 mg / dlExcretion: In urine as N-methyl nicotinic

acid

Deficiency:

PELLAGRA / Rose SicknessPellagra = Rough skin ( Italian

word)Characterised by 4 ‘D’1. Diarrhoea2. Dermatitis3. Dementia4. Death

Diarrhoea

Mild to severe with blood and mucus leads to weight loss

Associated with nausea and vomitingDermatitis:

In early stages, bright red erythema in feet, ankles, face, wrist, elbows, face - Increased pigmentation around neck “casal’s necklase.”

- PPt by sun exposure

Dementia:

Delirium( confusional state) is common in acute cases

Dementia (long term loss of the ability to think and reason clearly) in chronic cases

Irritability, inability to concentrate and poor memoryPostero lateral tract degenerationAtaxia (lack of muscle coordination which may affect

speech, eye movements, the ability to swallow, walking, picking up objects and other voluntary movements)

Spasticity

Causes : for Niacin deficiency

1. Dietary deficiency of Tryptophan Staple diet. Maize, corn – Niacytin

(bound) form and is unavailable. Sorghum (Jowar) – Contains Leucine. Leucine QPRT2. Lack of Vitamin B6: Kynureninase is PLP dependent enzyme

3. INH: Common ATT PLP

4. Hartnups disease : Tryptophan absorption is defective and Try is excreted in urine

5. Carcinoid syndrome: Tumor utilises Tryp. and converts it to Serotonin. So, no availability

6 Incidence is more in female. Oestrogen

metabolites Tryptophan

Niacin antagonists:

Pyridine 3 – sulfonic acid, 3 – Acetyl Pyridine

CLINICAL ASPECTS

1. Development Of fatty liver:Niacin takes up CH3 groups from

1 – c pool. Thus, excess N-methyl nicotamide produces fatty liver.

By reducing choline.

2.Effect on plasma lipids:Niacin reduces plasma lipid conc.

So, useful in HYPERLIPIDEMIA 3 – 6 g / day – Reduces cholesterol, β- Lp

and TG, Lp(a) Nicotinic acid inhibits the flux of FFA from

adipose tissue. So, acetyl coA pool is reduced and hence cholesterol is lowered by Nicotinamide

3. Therapeutic use:IV or oral Niacin produce

vasodilatation of cutaneous vessels and histamine release.

- Reaction is accompained by itching, burning and tingling.

- Nicotinamide is safer than Nicotinic acid.

PANTOTHENIC ACID

Pantos= everywhereSULPHUR containingChemistry: pantoicacid (derived valine)and β-

alanine (derived from alanine) linked by peptide linkage

Active form: COASH- pantoicacid+alanine+thioethanalomine+AMP

Biochemical reactions

Fatty acylcoAAcetyl coApropionylcoASuccinyl coHMGcoAFATTY ACID SYNTHASE COMPLEX

DIETARY SOURCES

Egg yolk, liver, yeast. legumes, whole grains,RDA:10mgDeficiency: noBurning feet syndrome (Gopalans syn):numbness and tingling,

hyperactive reflexes, weakness of extensor muscles, anemia