Vitamin C and Pantothenic Acid

8/12/2019 Vitamin C and Pantothenic Acid

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(ASCORBIC AND PANTOTHENIC ACIDS)


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VITAMIN C 1747 James Lind, Scottish Navalsurgeon, discovered a nutrient incitrus fruit prevented scurvy Waugh, Albert Szent Gyorgyi, andCharles Glen Kingelucidated structure and importance Also known as ascorbic acid , ameaning no)and scorbuticusscurvy)

Szent-Gyorgyi James Lind


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BIOSYNTHESIS OF ASCORBIC ACID

oAll plants and most animals except

some mammals and few birds

synthesize Vitamin C from glucose.

o Some animals have lost the enzyme

L-gu lonolactone ox idase

catalyzes conversion of L-gulonolactone to L-3-

ketogulonolactone


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ABSORPTION OF VITAMIN C

o

Absorbed through active transport and simple diffusion

o Two transporters :- 1) Sodium dependent

vi tam in C

transpo rter (SVCT)2) GLUT transporters

o SVCT1 and SVCT2 import reduced from, ascorbate,

across plasma membrane

o GLUT1,GLUT3 and GLUT4 only transfer

dehydroascorbic acid from of ascorbic acid.


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Most of

absorptionoccurs in

the distal

portion of

the small

intestine

with degreeof

absorption

decreasing

with

increased

intake of

the vitamin.


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o Susceptible to oxidat ionto dehydroascorbic

acid

Ascorbic acidDehydroascorbic

acid


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OXIDATION OF VITAMIN C

o Ascorbic acid oxidized by two successive

loses of single electron

o First monovalent oxidationformation of

ascorbyl free radical; reversible reaction

o Further oxidized to form dehydroascorbic

acid which undergoes irreversible

hydrolysis to form 2,3-diketo-L-gulonic

acid


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METABOLIC FUNCTION OF

VITAMIN C

1) Electron transpo rto Loses electrons easily because of reversible

monovalent oxidation to ascorby l radical

o Involved in many electron transport reactions

o Ascorbic acid regeneratedascorbyl ion reduced by

two enzymes

dehyd roasco rbate reductase

ascorbate cy tochrome-b5.


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OHO

O

OO

L-AscorbateAnion

O

HO O

O-

HO

OHO

CH2OHO

O O

-e-, -H+

+e-, +H+

-e-

+2 e- , +2H+

Dehydro Ascorbic Acid Reductase

Ascorbyl free radical

DehydroascorbicAcid

CH2OH CH2OH


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2) Ant iox idant func t ions

Antioxidant Activity Reacts and removes active oxygen species

Pro-oxidant Activity Reduces metals to their pro-oxidant forms


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3)Col lagen synthesis

o Helps in hydroxylation of proline and lysine inprocollagen molecule

o Catalyzed by prolyl hydroxylase and lysyl

hydroxylase

o Hydroxylation of procollagen necessary for

folding into triple helical structure


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4) Catecho lam ine biosyn thesis

o Serves as electron dono rfor dopam ine

monooxygenase

5)Carni t ine synthesis

o Ascorbic acid acts as a cofactor of two Fe2+

containing hydroxylases involved in synthesis

of carnitine


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CATECHOLAMINE BIOSYNTHESIS

Dopamine--Monooxygenase

Cu+ Cu2+

AscorbateAscorbyl free radical


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6)Tyros ine metabo l ism

Oxidative degradation of tyrosine by 2 oxidases :- 4-hyd roxyphenylpyruvate dioxygenaseand

homogent isate 1,2-dioxygenase

Former catalyzes oxidation and decarboxylation of

4-hydroxylphenylpyruvate to homogentisic acid

Latter requires ascorbate for tyrosine degradation


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7)Absorpt ion of iron

Keeps iron in fer rous form

(Fe2+)

8) Immune funct ion

Stimulate production of in terferons

Antibody IgG andIgM

Megadose of vitamin

C10g/day,

prevent common cold


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Life Stage Age Males (mg/day) Females(mg/day)

Infants 0-6 months 40 40

Infants 7-12 months 50 50

Children 1-3 years 15 15



Adolescents 14-18 years 75 65

Adults Above 19 90 75

Smokers Above 19 125 110

Pregnancy Below 18 ---- 80

Pregnancy Above 19 ---- 85

Breastfeeding Below 18 ---- 115

Breastfeeding Above 19 ---- 120


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Bone Formation in Guinea Pigs

S e c t i o n o f c o s t o c h o n d r a l

j u n c t i o n f r o m a g u i n e a p i g

d y i n g o f s c u r v y. S i l v e r

s t a i n w a s u s e d t o b r i n g

o u t a n y r e t i c u l u m b u t

t h e r e a r e n o n e - o n l y t h e

n u c l e i o f t h e i m p o t e n t

o s t e o b l a s t s s t a i n .

S e v e r e l y s c o r b u t i c a n i m a l

a f t e r 7 2 h o f a s c o r b i c a c i d

t r e a t m e n t ; f i b e r s o f

r e t i c u l u m h a v e a p p e a r e d

b e t w e e n t h e n u c l e i & h a v e

f u s e d i n s o m e a r e a s t o f o r m

a s t e o i d m a t r i x .


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In children, calledMoller-Barlowdisease,

seen in non-breastfed infants

VITAMIN C DEFICIENCY

Show lethargy, fatigue,rheumatic pains in legs,

muscular atrophy, skin lesions,

hemorrhages in many organs


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Vitamin CScurvy in

Human Scorbutic Rosary

Enlarged costochondral junctions

of scurvy resembles rickets -

lesions may feel sharper & may betender

X ray of a child withscurvy


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Vitamin CScurvy in Human

C h i l d i n s c o r b u t i c p o s i t i o n . B e c a u s e m o v e m e n t i sp a i n f u l , i n f a n t u s u a l l y l i e s o n i t s b a c k , m a k e s l i t t l ea t t e m p t t o l i f t l e g o r a r m h u r t s . L e g s m a y b e t e n d e ra n d s o m e t i m e s b o t h a r m s a s w e l l . U s u a l l y f i r s t s i g no f s c u r v y .


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Bone Lesions Scurvy

Calcified cartilage at

costachondral junction

Fractures between epiphysis andshafts of femur, tibia and fibula

Fracture at lower end of tibia


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Rebound Scurvy When h igh doses o f v i tamin C are taken

body excre tes i t rap id l y When ab rup t l y s t opped t h e body i s unab l e t o

immed ia t e l y r educe r ap i d e xc r e t i on r a t e Po t en t i a l ly r e su l t s i n v i t am in C de f i c i enc y


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Ascorbate Toxicity Nausea, abdominal cramps and diarrhea

Oxalate kidney stones

Decreases uric acid reabsorptionresulting in increased risk of gout

Interference with medical diagnostictests False positive or false negative to detectdiabetes

Individuals taking anti-clotting medicationmay counteract the effect if they take highdoses of vitamin C

Dangerous for people with iron overload

UL adults: 2000mg/d


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Other Potential FunctionsReduce stress (e.g. infections, smoking)

Mechanism unknown, but vitamin C

requirements increase during stress

Common cold? Disease prevention? Cancer, heart disease: inconclusive


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PANTOTHENIC ACIDDerived from the Greek word pntothen,

meaning from all quarters (everywhere)

R.J. Williamsand coworkers isolated and

named it pantothenic acid in 1933

Critical role in metabolism since it playsimportant role as acylation factorscoenzyme-A (CoA) and acyl-carrierprotein(ACP)


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SOURCES OF PANTOTHENIC ACID

Meat- l iverand heart

particularly Mushrooms, avocados,

broccol iand some yeast

Whole grains- localized in the

outer layer Richest source of this vitamin

co ldwater f ish ovar ies

(2.3mg/g) and royal jel ly

(0.5mg/g) 15-50% loss from cooking

meat and 37-78% from heat

processing vegetables


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Age group Age Requirements(in mg per day)

Infants 06 months 1.7

Infants 712 months 1.8

Children 13 years 2

Children 48 years 3

Children 9-13.5 years 4

Adolescents 1418 years 5

Adult men 19 years and older 5

Adult women 19 years and older 5

Pregnant women 6

Breastfeeding women 7

RD FOR P NTOTHENIC CID


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ABSORPTION OF PANTOTHENIC ACIDOccurs in food mainly as CoA and ACP

Degraded in lumen of intestine to

release 4-phosphopantetheine

It is then dephosphory latedto yield

pantetheine which is rapidly convertedto panto thenic acidby pantetheinase


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pantetheinase


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METABOLISM OF PANTOTHENIC ACID

a) Coenzyme A biosynthesis Synthesis of CoA from pantothenic acid requires

five basic steps

Four moles of ATP required

In cytosol1) Pantothenic acid

4- phosphopantothenic acid

2) 4- phosphopantothenic acid

4-phosphopantothenylcysteine

Pantothenate kinase

ATP dependent

Phosphopantothenyl

cysteine synthase

ATP dependent


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3) 4-phospho 4-phospho

pantothenylcysteine pantetheine

In the mitochond r ial inner membrane

4) 4-phospho dephosphopantetheine CoA

5) Dephospho CoA CoA

Phosphopantetheinyl

cysteine decarboxylase

Phosphopantetheine

adenyltransferase

Dephospho CoA kinase

ATP dependent

ATP dependent


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FUNCTIONS OF Co

in TCA cycle, assist decarboxylation of -ketoglutarate

used (acetyl CoA) for synthesis of fatty acids (e.g.: cholesterol)

used in oxidation of amino acids

used in acetylation of alcohols, amines and amino acids

used in acetylation of proteins like histones

b) A l C i P t i


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b)Acy l-Carr ier Pro teinb iosynthes is

ACP synthesized as apoprotein lackingprosthetic group

Require pantothenic acid in the form ofprosthetic group, 4-phosphopantetheine

That group, 4-phosphopantetheine,transferred to ACP from CoA by action of4-phophopantetheine apoACPtransferase


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Pantothenic AcidDeficiencyDeficiency is rare; the burning

feet

Goose stepping - swineCannot bend hock joint (nervous

system degeneration)

Reduced growth, dermatitis,

diarrhea


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Deficiency

Very rare in humans and common in animals likedogs, chicken etcTissue CoA levels are not altered in pantothenatedeficiencyNausea, abdominal pain, headache and numbness

or tingling in the limbs and extremitiesMuscle cramping and lack of coordination

P t th i id d fi i Chi k


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Pantothenic acid deficiency - Chick

Dermatitis in chick on

pantothenic acid deficient diet

Three weeks after calcium

pantothenate added to diet, skin

lesions cured


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Pantothenic acidAn essential vitamin to humans

and animals for proper growth,reproduction, and common

physiological conditions.

Involved in multiple metabolicpathways that uses the coenzymes

of CoA and acyl carrier protein.


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Water Soluble Vitamins

Eight B vitamins, Vitamin C

Absorbed via blood

Transported freely in bloodExcesses excreted in the urine

Toxicity with over supplementation

Must be consumed on a regular basisSteam rather than boil vegetables


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To minimize vitamin losses, wrap cut fruits and

vegetables or store them in airtight containers.


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Try topical vitamin C.

Vitamin Ccan increase collagen production,

protect against damage from UVA

and UVB rays,

correct pigmentation problems, andimprove inflammatory skin

conditions.

Most research points to L-ascorbic

acid as the most potent for wrinkle

relief.

D it hi iti


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The Nobel Prizewinning scientist LinusPauling was the first to

claim that vitamin Ccould extend your life.Dr. Pauling tookbetween 12,000 and18,000 mg of vitaminC every day for 40years.

Despite his critics

Linus Pauling was right.


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In 1998 Japanese

study tested vitamin

Cs effect on

telomeres. It was

found that raisingthe level of vitamin

C in the cells could

slow down the lossof telomeres up to

62%

The telomere

preserving, anti-

aging benefit of

vitamin C

appears to begin

at about 500 mg,

twice a day.
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Take it with food to avoid an upset

stomach!!
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An in vivo study supportsearlier research showing thatadding ascorbic acid and sugarto green tea may increase theamount of antioxidants thebody is able to absorb - MarioFerruzzi associate professor offood science and nutrition.


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Researchis stillbeing developed to

support the many

advantagesthat these

vitamins play

in our diet.


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Documents

Vitamin C and Pantothenic Acid