Introduction

Vitamins are an organic chemical compound which the body requires in small amounts for the metabolism and to protect your health.

Vitamins assist the body in Vitamins assist the body in functioning properly by functioning properly by helping in the formation of helping in the formation of hormones, blood cells, hormones, blood cells, nervous-system chemicals nervous-system chemicals and genetic growth. An and genetic growth. An over dose can be harmful over dose can be harmful to your health.to your health.

The Body & Vitamins

The body can only produce one vitamin naturally by itself. This is vitamin D. All other vitamins that the body requires to function properly have to be derived from the diet. Lack of vitamins can have a serious affect on your health and may end in metabolic and other dysfunctions.

Vitamin Groups

Vitamins are divided up into two main groups which are fat-soluble vitamins and water-soluble vitamins. Fat-soluble vitamins are usually found in foods that contain fat.

The body stores the fat The body stores the fat soluble vitamins and soluble vitamins and because of this, people because of this, people don’t usually need to don’t usually need to make a special effort to make a special effort to include them in their include them in their diet. diet.

Vitamin Groups

Water soluble vitamins can’t be stored in the body for a long time and have to be replenished everyday.

In some cases when In some cases when it’s not possible to it’s not possible to obtain these obtain these vitamins in a regular vitamins in a regular diet, they have to be diet, they have to be acquired by other acquired by other vitamin vitamin supplements.supplements.

Water-Soluble Vitamins

• Water soluble• Readily excreted – expensive urine• Can be lost from food by cooking/storage• Typically work as part of enzymes in metabolism

• Relatively high absorption rate• Severe deficiencies rare

• Vitamins – Niacin, Thiamine, Folic Acid, Riboflavin, B12, and C.

Thirteen complete Vitamins Water soluble Vitamins Vitamin B1 (Thiamin) Vitamin B2 (Riboflavin) Vitamin B6 (pyridoxine) Vitamin B12

(Cyanocobalamin) Vitamin Biotin (Vitamin H) Vitamin C (Ascorbic Acid) Vitamin P (Bioflavonoids) Niacin (Niacinamide)

Fat-Soluble Vitamins Vitamin A & Beta carotene Vitamin D Vitamin E Vitamin F (unsaturated fatty

acids) Vitamin K (Menadione)

Vitamin K cycle

NH

R

R

C H C H2 C H2

C = O

-C O 2

NH

R

R

C H C H2 C H

C = O

-C O 2

-C O 2

K (re d )

carboxylase

epoxidereductase

vitam in Kreductase

coum arin sK (e p o x )

K (o x )

C a

G L U res id u e

G L A res id u e

O + C O2 2 H O + H2+

D ie t

Thrombin Activation

co llagen

WO UNDv W F

endo th eliu m

p la te le tPL surfa c e

C a

C a

Va

Xa

C ircu la tio n

N H2C O O H

G la G la

P ro -T h ro m b in

SS

p ro teo ly t ic cu t

N H2C O O H

G la G la

T h ro m b inP ro -

SS

The common pathway

p ro th ro m bin * th ro m bin

fib rino ge n

F ib rin m on om er

F ib rin po ly m erC L O T

* X a

X III X IIIa

Va V

C o m m o np a thwa y

Thiamine pyrophosphate (TPP) is a derivative of thiamine (vitamin B1). Nutritional deficiency of thiamine leads to the disease beriberi. It affects especially the brain, because TPP is required for CHO metabolism, and the brain depends on glucose metabolism for energy.

th iam ine pyrophosphate (T P P )

N

NH 3C NH 2

CH 2S

C

N

H 3CCH 2 O P O P O

O O

CH 2

H

O O

+

acid ic H +

FAD (Flavin Adenine Dinucleotide is derived from the vitamin riboflavin. The dimethylisoalloxazine ring system undergoes oxidation/reduction.

FAD is a prosthetic group, permanently part of E3.

Reaction: FAD + 2 e- + 2 H+ FADH2

C

CCH

C

C

HC

NC

CN

NC

NHC

H3C

H3C

O

O

CH2

HC

HC

HC

H2C

OH

O P O P O

O

O-

O

O-

Ribose

OH

OH

Adenine

C

CCH

C

C

HC

NC

C

HN

NH

C

NHC

H3C

H3C

O

O

CH2

HC

HC

HC

H2C

OH

O P O P O

O

O-

O

O-

Ribose

OH

OH

AdenineFAD FADH2

2 e + 2 H+

dimethylisoalloxazine

Glossitis (Fig. 10-4)

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Dermatitis of Pellegra (Fig. 10-5)

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Lipoamide includes a dithiol that undergoes oxidation/ reduction.

S CH2

CH2

CHS

CH2 CH2 CH2 CH2 C NH (CH2)4 CH

NH

C O

O

HS CH2

CH2

CHHS

CH2 CH2 CH2 CH2 C NH (CH2)4 CH

NH

C O

O

2e + 2H+

lipoamide

dihydrolipoamide

lysine lipoic acid

The carboxyl at the end of lipoic acid's hydrocarbon chain forms an amide bond to the -amino group of a lysine residue of E2, yielding lipoamide.

A long flexible arm, including hydrocarbon chains of lipoate and the lysine R-group, links each dithiol of lipoamide to one of two lipoate-binding domains of E2.

S CH2

CH2

CHS

CH2CH2CH2CH2CNH(CH2)4 CH

NH

C O

O

HSCH2

CH2

CHHS

CH2CH2CH2CH2CNH(CH2)4 CH

NH

C O

O

2e + 2H+

lipoamide

lysine lipoic acid

The final electron acceptor is NAD+.

Coenzym e A -SH + HO C

O

CH 3

Coenzym e A -S C

O

CH 3 + H2O

acetic acid

acetyl-CoA

N

R

H

CN H 2

O

N

R

CN H 2

OH H

+

2 e + H

+

N A D + N A D H

In the overall reaction catalyzed by the Pyruvate Dehydrogenase complex, the acetic acid generated is transferred to coenzyme A.

Sequence of reactions catalyzed by Pyruvate Dehydrogenase complex:

1. The keto C of pyruvate reacts with the carbanion of TPP on E1 to yield an addition compound.

The electron-pulling (+) charged N of the thiazole ring promotes CO2 loss. Hydroxyethyl-TPP remains.

2. The hydroxyethyl carbanion on TPP of E1 reacts with the disulfide of lipoamide on E2. What was the keto C of pyruvate is oxidized to a carboxylic acid, as the lipoamide disulfide is reduced to a dithiol.

The acetate formed by oxidation of the hydroxyethyl is linked to one of the thiols of the reduced lipoamide as a thioester (~).

Sequence of reactions (continued)

3.Acetate is transferred from the thiol of lipoamide to the thiol of coenzyme A, yielding acetyl CoA.

4.The reduced lipoamide, swings over to the E3 active site. Dihydrolipoamide is reoxidized to the disulfide, as 2 e- + 2 H+ are transferred to a disulfide on E3 (disulfide interchange).

5.The dithiol on E3 is reoxidized as 2 e- + 2 H+ are transferred to FAD.

The resulting FADH2 is reoxidized by electron transfer to NAD+, to yield NADH + H+.

Acetyl CoA, a product of the Pyruvate Dehydrogenase reaction, is a central compound in metabolism.

The "high energy" thioester linkage makes it an excellent donor of the acetate moiety.

a c e t y l - c o e n z y m e A

H 3 C C

O

S C o A

View an animation of the Pyruvate Dehydrogenase reaction sequence.

Acetyl CoA functions as: input to Krebs Cycle, where the acetate moiety

is further degraded to CO2. donor of acetate for synthesis of fatty acids,

ketone bodies, & cholesterol.

glucose-6-P

Glycolysis

pyruvate fatty acids

acetyl CoA ketone bodies cholesterol

oxaloacetate citrate

Krebs Cycle

Biosynthesis of Amino Acids: Transaminations

Amino Acid1 +-Keto Acid2 Amino Acid2 +-Keto Acid1

NH3+

-O2CCH 2CH2CHCO 2-

Glutamate

OR-CCO 2

-+

O-O2CCH 2CH2CCO 2

-

-Ketoglutarate

NH2

R-CHCO 2-

+

Pyridoxal phosphate (PLP)-Dependent Aminotransferase

Transaminations: Role of PLP

N

C

CH2OPO3-2HO

H3C

N CHCH2CH2CO2-

N

HNH3+

CO2-

CHO

CH2OPO3-2HO

H3C

H

N

H

CH2

CH2OPO3-2HO

H3C

N CCH2CH2CO2-

H

CO2-

N

CH2NH2

CH2OPO3-2HO

H3C

O

H

H2O

-O2CCH 2CH2CCO 2-

+ +

++

-O2CCH 2CH2CHCO 2-

H2O

Tautomerization

Vitamin-Coenzymes in Amino Acid Metabolism

• Vitamin B-6 : pyridoxal phosphate– Enzymes that bind amino

acids use PLP as coenzyme for binding

• Transaminases• Amino acid

decarboxylases• Amino acid deaminases

Absorption of Vitamin B-12 (Fig. 10-10)

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Vitamin-Coenzymes in Amino Acid Metabolism

• Vitamin B-12– Catabolism of BCAA

• Methyl-malonyl CoA mutase (25-9 &10)

Vitamin-Coenzymes in Amino Acid Metabolism

• Vitamin B-12– Methionine

synthesis/recycling• Methionine as a

methyl donor– Choline and

creatine synthesis– Homocysteine is

product– HCys -> Met

requires B-12

Vitamin-Coenzymes in Amino Acid Metabolism

• Folacin: Tetrahydrofolate (THF)– Carrier of single

carbons• Donor & receptor• Glycine and serine• Tryptophan degradation• Histidine degradation• Purine and pyrimidine

synthesis

Ascorbic Acid Structure

(AscH2

)

O

OH

OHO

HO

OH

AscH2 is a Di-acid

At pH 7.4, 99.95% of vitamin C will be present as AscH-; 0.05% as AscH2 and 0.004% as Asc2-. Thus, the antioxidant chemistry of vitamin C is the chemistry of AscH- .

O

OH

OHO

HO

OH

O

OH

OHO

O

OH

O

O

OHO

O

OH

pK1 = 4.1 pK2 = 11.8

AscH2 AscH- Asc2-

Forms of Ascorbate

pK = 4.1

pK = 11.8

pK = -0.86

O O

OHO

OHOH

HOO O

HOHO

OHOH

OH

HO

+H+ -H+

+H+ -H+

O

OH

OHO

HO

OH

AscH2

O

OH

OHO

O

OH

AscH-

+H+ -H+

O

O

OHO

O

OH

Asc2

-e

-e -e

Asc

O

O

OHO

O

OH

O

O

OHO

O

OH

DHA

+H2O-H2O

+H2O

-H2O

DHAA (2) DHAA (1) (>99%)

(pK ~ 8-9)

O

OH

OHO

O

OH

AscH

Ascorbate Falling Apart

+H2O

+2H+

-2H+

AscH2

HO

OH

O

OH

O

HO

-e

Asc

HO

OH

O

O

O

ODHA

HO

OH

O

O

O

O

+e

-e

+e

DHA

HO

OH

O

O

O

O

2,3-diketo-L-gulonic acid

L-xylonicacid

L-lyxonic acid

C

C

C

C

C

CH2OH

OHO

OH

HO

O

O

H

H

C

C

C

C

CH2OH

OHO

OH

OH

HO H

H

H

C

C

C

C

CH2OH

OHO

OH

HO

HO

H

H

H

+

L-xylose

CH2OH

C

C

C

CH2OH

OH

HO

O

H

L-threonicacid

oxalic acid

+

C

C

C

CH2OH

OH

HO

O OH

HC

C

O OH

OHO

AscH- is a Donor Antioxidant

AscH- donates a hydrogen atom (H or H+ + e-) to an oxidizing radical to produce the resonance-stabilized tricarbonyl ascorbate free radical. AscH has a pKa of -0.86; thus, it is not protonated in biology and will be present as Asc-.

AscAscH

O

OH

OHO

O

OH

R+ RH+

O

O

HO

O

OH

O

Ascorbate, Summary

Ascorbate is a versatile, water soluble, donor, antioxidant.

Thermodynamically, it can be considered to be the terminal, small-molecule antioxidant.

AscAscH

O

OH

OHO

O

OH

R+ RH+

O

O

HO

O

OH

O