Pantothenic acid

Historical Background
VitB5.
Pantothenic acid.

Pantothenate.
1st discovered at 1919.

Chemical structure
Formula C9H11O5N. Amide between pantoic acid and B-alanine

pantoic acid

-alanine

Characterize by:
Water soluble vitamin.

Appearance: yellow colour, viscous oil.

Un stable to heat, alkali and acid. Hydrolytic cleavage to:

B-alanine and 2-4dihydroxy 3,3 dimethyl butyrate

Has two active forms in the body:

Coenzyme A: Acyl carrier protein:

Coenzyme adapted from cystiene ,pantothenate and adenosine triphosphate

Its small negatively charge alpha helical protein with high degree of structural and amino acid similarity.

Active forms:
Coenzyme A

Active forms:
Acyl carrier protein

VitB5 Sources
Pantos
means everywhere

Pharmacokinetics:
In foods, most pantothenic acid is in the form of :

CoA or acyl carrier protein (ACP). For the intestinal cells to absorb this vitamin, it must be converted into free pantothenic acid. Within the lumen of the intestine, CoA and ACP are Hydrolyzed into 4'-phosphopantetheine. This then dephosphorylated into pantetheine Pantetheinase, an intestinal enzyme, then hydrolyzes pantetheine into free pantothenic acid.

Absorption:
The free pantpthenic acid then absorbed

by either: - active transport (Na dependant). - passive transport. According to the concentration.

Transport:
Carried in the plasma and erythrocyte.
Enter erythrocyte through passive diffusion. Distributed to different tissues(brain, heart,

kidney, liver). Enter the cell through Na co transport. Converted again to the tissue form : CO enzyme A.

Metabolism
The synthesis of CoA from pantothenate is

regulated primarily by pantothenate kinase, an enzyme that is inhibited by the pathway end products, CoA and acyl CoA. Thus CoA production does not reflect the amount of available pantothenate

Coenzyme A synthesis
Pantothenate
pantothenate kinase

4-phosphopantothenate Cyestiene ppc synthetase 4-phospho -N-pantothenyl cystiene ppc decarboxylase 4- phosphopantetheine pp Adenyl transferase Desphosho coA

Co A: synthesis
1\ Pantothenate is phosphorylated to 4'phosphopantothenate. 2\ A cysteine is added to 4'-phosphopantothenate to form 4'-phospho-N-pantothenoylcysteine (PPC) . 3\ PPC is decarboxylated to 4phosphopantotheine. 4\ 4'-phosphopantotheine is adenylylated to form dephospho-CoA. 5\ Finally, dephospho-CoA is phosphorylated using ATP to coenzyme A.

ACP synthesis:
Synthesized from Apo ACP protien and Co enzyme A

Excretion:
Excreted in the urine as free pantothenic acid or 4

phosphopantethenate. In the kidney pantothenic acid either: Reabsorped. Tubular secretion. Amount excreted reflect the dietary intake. Biomarkers detected by radioimmunoassay.

Function of Vit B5
Metabolic functions.

Other roles.

Metabolic function:

 Formation

of acetyl co A.

Co A : Functions
Citric acid cycle: acetyl residues (in the form of

acetyl Co A) are catabolised.

Fatty acid synthesis & oxidation: fatty acids are

both synthesized from and oxidized to acetyl Co A.

Cholesterol synthesis: Acetyl Co A is the source

of all carbon atoms in cholesterol.

Co A : Functions
Biosynthesis of acetylcholine:

choline + acetyl Co A

cholineacetyltransferase

Acetylcholine + Co A.
Acetylation reactions: e.g. drugs, post-

translational modification of some proteins.

ACP: Function
In mammals the fatty acid synthase system is a multienzyme polypeptide complex. ACP is part of that complex.

Other roles:
Pantothenic acid enhance red blood cell

production and maintain normal haemoglobin level Enhance the immune system through regulating stress hormones Maintain the heart healthy through : lower the cholesterol level maintain normal blood pressure Reduce the acne

Recent research:
Diabetic ulceration Diabetic peripheral polyneuropathy Testicular torsion Rheumatoid arthritis Athletes' performance

Age group Requirements

Age Infant (0-6) month Dosage 1.7 mg

Infant (7-12) month

Children(1-3) yrs Children (4-8) yrs Children (9-13)yrs Adult men and women(+14)yrs Pregnant women

1.8 mg
2mg 3mg 4mg 5mg 6mg

Breastfeeding women
United Kingdom RDA: 6 mg/day

7mg

Deficiency:
Pantothenic acid deficiency is

exceptionally rare and has not been thoroughly studied. Patients with digestive problem In starvation ,malnutrition cases and limited volunteer trials.

Clinical manifestations:
Fatigue,irratibilty and apathy, dermatitis, alopecia and ulcer numbness, paresthesia, and muscle cramps HYPOGLYCEMIA Adrenal insufficiency and hepatic encephalopathy

Treatment
All symptoms corrected and

reversed with the return of pantothenic acid,either by : Food Or Synthetic supplementation.

Supplementation
Pantothenol More stable form of the vitamin and is often found in multivitamin supplements Calcium pantothenate more stable than pantothenic acid in the digestive mentation may improve oxygen utilization efficiency and reduce lactic acid accumulation in athletes.

Antagonists:
Methylpantothenic acid.
Desthio-coenzymeA. Hopantenate.

Toxicity
no Tolerable Upper Level Intake

(UL) has been established for the vitamin. Toxicity of pantothenic acid is unlikely massive doses (e.g., 10 g/day) may only yield mild intestinal distress

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