niacin and pantothenicacid
TRANSCRIPT
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DR. P. HAVILAH .M.DASSOCIATE PROFESSORDEPT OF BIOCHEMISTRY
SANTHIRAM MEDICAL COLLEGE.
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NIACIN ( VIT B3)
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NIACIN
Synonyms:Nicotinic acid, P-P factor, Pellagra
preventing factor of gold bergerChemistry:
Pyridine 3 – carboxylic acid
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NIACIN NIACINAMIDE
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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)
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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
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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-
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NADP+
OII
0-P-OO
One more phosphoric acid is
attached to ribose of AMP
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NAD+ - reqd for ADP –ribosylation of proteins
In DNA – repair
NADH enters ETC and releases 3 ATP
NADPH used for reductive biosynthesis
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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
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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+
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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)
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Lipid metabolism7.β-hydroxy acylcoA dehydrogenase(. β
oxidation)8. . β -hydroxy butyrate (ketolysis)Protein metabolism9. Glutamate dehydrogenase10. Glycine cleavage11.Ketoacid dehydrogenase
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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.
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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
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Both NAD+ / NADP+ requiring enzyme
1. Glutamate dehydrogenase ( Glutamate αKGA
+ NH3) 2. ICD ( ISO citrate Oxalosuccinate3. Retinine reductase
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Dietary sources:Animal : Liver, Kidney, Meat, FishVegetables: Legumes (Peas, beans, lentils),
nuts coffee, Tea
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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
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Deficiency:
PELLAGRA / Rose SicknessPellagra = Rough skin ( Italian
word)Characterised by 4 ‘D’1. Diarrhoea2. Dermatitis3. Dementia4. Death
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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
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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
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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
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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
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Niacin antagonists:
Pyridine 3 – sulfonic acid, 3 – Acetyl Pyridine
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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.
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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
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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.
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PANTOTHENIC ACID
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Pantos= everywhereSULPHUR containingChemistry: pantoicacid (derived valine)and β-
alanine (derived from alanine) linked by peptide linkage
Active form: COASH- pantoicacid+alanine+thioethanalomine+AMP
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Biochemical reactions
Fatty acylcoAAcetyl coApropionylcoASuccinyl coHMGcoAFATTY ACID SYNTHASE COMPLEX
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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