Lecture 6

Vitamins and Coenzymes

Outline

• Classification of vitamins

• Structure of vitamins

• Features and functions of

vitamins as coenzyme

•Some enzymes require cofactors for activity

-- Essential ions

mostly metal ions: Zn2+,Fe2+

-- Coenzymes (organic compounds)

Vitamin-derived coenzymes-derivatives of vitamins.

Introduction

Vitamins

Definition ： Vitamins are organic nutrients that are required in small quantities for a variety of biochemical functions and which, generally, cannot be synthesized by the body and must therefore be supplied by the diet.

History

Thiamine was discovered in 1912 & was thought to be a vital amine compound & thus the term vitamin was invented

Vita=vital for life Min=amine

Properties Vital to life; are essential Organic compounds Individual units; not linked in chains Do not provide energy Assist with release of energy (coenzymes) Needed in small amounts: micro/milli grams Fruits and vegetables are a primary source

Nomenclature and function

Vitamin A: prevent night blindness Vitamin B: anti-beriberi factor Vitamin C: anti-scurvy factor Vitamin D: anti-ricket factor Vitamin E: for reproduce properly Vitamin K: concerned with coagulatio

n

Water Soluble Vitamin C B Vitamins

Thiamine (B1) Riboflavin (B2) Niacin Pantothenic Acid Biotin Pyridoxine (B6) Folic Acid Vitamin B12 (cyanoc

obalamin)

Lipid Soluble Vitamin A Vitamin D Vitamin E Vitamin K

Classification

Energy-releasing

Hematopoietic

Water-soluble vitamins

Common features: 1.Water soluble 2.Easy to be discharged through urine. Rarely accumulated to the toxic concentrations. 3.Their storage is limit. Must be provided regularly.Vitamin B12 is the only water-soluble vitamin

that can be stored in the liver for many years.

B Vitamins

1. Thiamin (B1)2. Riboflavin (B2)3. Niacin4. Pantothenic Acid5. Biotin6. Vitamin B6

7. Folic Acid8. Vitamin B12

• Indispensable for metabolism.• B vitamins help the body to produce energy. • B complex vitamin are necessary for healthy skin, hair, eyes and liver, also help the nervous system function properly.

1. Vitamin B1 (Thiamine )• In 1897 Christiaan Eijkman discovered

that fowl fed on a diet of cooked, polished rice developed paralysis, which could be reversed by discontinuing rice polishing.

• He attributed that to a nerve poison in the endosperm of rice, from which the outer layers of the grain gave protection to the body.

• Eijkman was awarded the Nobel Prize in Physiology and Medicine in 1929, because his observations led to the discovery of vitamins.

N

N

CH3

CH2

NH2S

CH

N+

CH3

CH2 CH2 O P

OH

O

O P

O

OH

OH

Pyrimidine ringThiazole ring

Reactive carbon atom

Thiamine: named as the "thio-vitamine" ("sulfur-containing vitamin")

Active form :Thiamine pyrophosphate (TPP or cocarboxylase)

Biochemical function

﹡TPP: co-enzyme of oxidative decarboxylation of α–keto acids and transketolase, involved in carbohydrate metabolism. ﹡with effects in the nerve conduction, inhibiting the cholinesterase activity.

Food Sources of thiamin

Recommended Dietary Allowance(RDA): M:1.2mg/d ， F:1.1

mg/d Most exceed RDA in diet Surplus is rapidly lost in

urine; non toxic Sources

Unrefined cereal grains and meat ； seeds, nuts, legumes

Deficiency of Thiamin

• Thiamine was named "the anti-beriberi factor ”(or antineuritic vitamin) (1926)

Beriberi: The word is from a Sinhalese phrase meaning "I

cannot, I cannot", the word being doubled for emphasis.

a neurological and cardiovascular disease Weakness, nerve degeneration, irritability, poor

arm/leg coordination, loss of nerve transmission, edema, heart failure.

Beriberi

2. Vitamin B2 (riboflavin) Vitamin B2, also commonly called riboflavin, gets it

s name from its color. The root of this word is the Latin word "flavus" meaning "yellow."

Vit B2

FMN AMP

FAD

ⅠⅡⅢN

N

C

NH

N

C

O

O

CH3

CH3

CH3

HCOH

HCOH

HCOH

H2C PO

OH

O

O

OH

O

PO

CH3O

OHOH

N

N

N

N

NH2

• Active form (coenzyme): • flavin mononucleotide (FMN) • flavin adenine dinucleotide (FAD)

Biochemical function

FMN and FAD are the prosthetic group of oxidoreductases with function of transmitting hydrogen, they play key roles in energy metabolism.

Proteins with FAD or FMN attached to them are often referred to as flavoproteins.

Food Sources of riboflavin

Adequate amounts of B2 is present in eggs, milk, meat & cereals.

Destroyed by ultraviolet light & irradiation

• RDA ： M: 1.4mg/d ， • F: 1.2mg/d

Deficiency

Symptoms associated with riboflavin deficiency include

Glossitis （舌炎） Seborrhea （皮脂溢出） Angular stomatitis （口角

炎） Cheilosis （唇干裂） Scrotitis （阴囊焱） Photophobia （畏光）

uncommon

3. Vitamin PP (niacin, pellagra preventive factor)

﹡ Vitamin PP nicotinic acid

nicotinamide

﹡Active form (coenzyme) Nicotinamide adenine dinucleotide (NAD+) Nicotinamide adenine dinucleotide phosphate (NADP+)

•The name 'niacin' was derived from “nicotinic acid + vitamin”

Pyridine derivative

NAD+ (Nicotinamide adenine dinucleotide) , R: H

NADP+ (Nicotinamide adenine dinucleotide phosphate), R: P O

OH

OH

adeninenicotinamide

Biochemical function

﹡NAD+ and NADP+: coenzyme of dehydrogenases, transfer of hydrogen.

Food Sources of Vit PP and Deficiency

Food Sources Niacin is found in unrefined and enr

iched grains and cereal,milk,and lean meats, especially liver. Limited quantities of niacin can also be obtained from the metabolism of tryptophan.

Deficiency Pellagra(Italian:rough skin) Symptoms: three Ds: dermatitis

（皮炎） , diarrhea （腹泻） , dementia （痴呆） , if not treated may rarely lead to death (4th D)

Mostly seen among people whose staple diet is corn or maize.

4. Pantothenic acid

Its name is derived from the Greek “pantothen” meaning "everywhere“. It is found in numerous foods and also is synthesized by intestinal bacteria.

HO CH2 C CH

CH3

CH3 OH

C

O

NH CH2 CH2 C

O

OH

pantoic acid -alanine

Pantothenic acid

Biochemical function﹡CoA and ACP are coenzyme of acyl transferase ， transfer of acyl.

Active form : • coenzyme A (CoA) • 4-phosphopantetheinyl: acyl carrier protein (ACP)

5. Biotin (anti-egg white injury factor)

• The name biotin is taken from the Greek word bios meaning "life." • It is necessary for cell growth, the production of fatty acids, and the metabolism of fats and amino acids.

Imidazole ring

Thiophene ring

Biochemical function• Biotin is covalently bound to the ε-amino groups of lysine residues of biotin-dependent enzymes. • Biotin: co-enzyme of carboxylase, the carrier of activated carbon dioxide(CO2).

Biotin - Food SourcesBiotin - Food Sources

Widespread in foodCheese, egg yolk, liver, peanut

butter, soybeans, fish Synthesized by GI (gastrointestinal

) bacteria.

Biotin DefficiencyBiotin Defficiency

Deficiency: rare Depression Numbness （麻痹） Lethargy Dermatitis （皮炎）

Did You Know? Eating large amounts of raw egg white can lea

d to biotin deficiency Raw egg whites contain a glycoprotein (A

vidin) which tightly binds biotin and prevents its absorption from the intestine; cooking denatures protein.

• Avidin was first isolated from raw chicken egg white by Esmond Emerson Snell

6. Vitamin B6 (pyridine derivatives)

﹡Three forms of vitamin B6:

Pyridoxine, pyridoxal, pyridoxamine

﹡Active form : Pyridoxal-Phosphate(PLP), pyridoxamine-Phosphate

Biochemical function﹡Coenzyme of amino acid aminotransferase, decarboxylas

e, and - amino-- levulinate synthase （ ALA synthase ）

• Most protein-rich foodssuch as meat, fish, andpoultry provide amplevitamin B6 ; somevegetables and fruitsare good sources, too.

Food Sources of Vit B6

Vitamin B6 Deficiency

Overt deficiencies are rare Isoniazid therapy (the first-line

antituberculosis medication) can induce VitB6 deficiency.

Manifestations Stomatitis, glossitis Dermatitis Irritability, confusion, depression Anemia

7. Folic acid (or folate)

﹡Active form: Tetrahydrofolate (THF or FH4)

• Folic acid or folate derive their names from the Latin word folium (which means "leaf"). • Obtained from yeasts and leafy vegetables as well as animal liver.

glutamic acidpteridine para-aminobenzoic acid (PABA)

FH4 (or THF)

Biochemical function FH4 : coenzyme of transferase of one carbon unit. The N5 and N10 of FH4 participate in the transfer of one carbon units.

N5—CH3—FH4

N5 、 N10—CH2—FH4

N5 、 N10=CH—FH4

N10—CHO—FH4

N5—CH=NH—FH4

Major FunctionsNew cell synthesis - GI tract, RBCProtein synthesisDNA/RNA synthesisIncreased needs w/ pregnancy

It is especially important during periods of rapid cell division and growth.

Folic Acid - Food SourcesFolic Acid - Food Sources

“Foliage” - green leafy vegetables, legumes, organ meats, orange juice, sunflower seeds, fortified grains.

Can be destroyed by heat and oxygen

Folic Acid - DeficiencyFolic Acid - Deficiency

Megaloblastic anemia (macrocytic anemia) An anemia (of macrocytic classification) that resu

lts from inhibition of DNA synthesis in red blood cell production.

This is often due to deficiency of vitamin B12 and/or folic acid.

Pregnant or lactating women may require folic acid supplementation. Folic acid deficiency in pregnant women may cau

se neural defects in the fetus.

Megaloblastic Anemia

8. Vitamin B12 (cobalamin, anti-pernicious anemia vitamin)

It is the most complicated vitamin and contains the biochemically rare element cobalt.

Active form:

Methylcobalamin; 5 -deoxyadenosylcobalamin

(R ： -CH3)

(R ： 5`-deoxyadenosine) Corrin ring

Dimethylbenzimidazole(DMB)

Biochemical function and deficiency

﹡Biochemical function ： methyl transfer

﹡Deficiency ： , Megaloblastic anemia (pernicious anemia), nerve disease , high blood level of homocysteine.

Food Sources of Vitamin B12

Vitamin B12 is a unique vitamin, synthesized by only microorganisms and not by animals and plants.

It is naturally found in meat (especially liver and shellfish), milk and eggs. Animals, in turn, must obtain it directly or indirectly from bacteria.

Causes of Vitamin B12 Deficiency

Vitamin B12 deficiency is rarely due to an absense of the vitamin in the diet.

It is much more common in patients who fail to absorb the vitamin from the intestine, resulting in pernicious anemia.Lack of intrinsic factor

(IF)

Pernicious Anemia(PA)

The classic description of patient with PA Lemon colored skin (anemia/icterus) Shiny tongue (atrophic glossitis) Mentally sluggish Shuffling broad gait

B Vitamins Coenzyme RolesThiamin B12BiotinPantothenic

AcidNiacin FolateB6RiboflavinVitamin

FMNTPP NADFAD PLPNADP THF CoA Biotin B12Coenzyme

Protein Metabolism Fat MetabolismCarbohydrate Met

E N E R G Y

NAD PLP

THF B12 NAD

TPP FAD FMN

CoA B12

NADFAD FMN

CoA B12

PLP

B12

NADP

Biotin

9. Vitamin C （ ascorbic acid ）

Water solublesour taste (acid)Six-carbon polyhydroxy compoundStrong antioxidant

OO

HO OH

C CH2OH

H

OH

1

2 3

4

C

C

CH

CH2 OH

OH

H

OH

C

C

O

OOH

14

C

C

CH

CH2 OH

O

H

OH

C

C

O

OO

14

£ 2H

£«2H

Vitamin CReduced state

Dehydro-vitaminC Oxidation state

﹡Biochemical function ： Redox reaction, Hydroxylation, Synthesis of collagen protein ， Absorbance of ferralia protects it from oxidation Antioxidant = Protectant Protects tissue from oxidative stress

Food Sources of Vitamin C---- fresh fruit and vegetables

• Essential nutrient – must get from diet Animals can actually synthesize from glucose, but humans cannot

ScurvyScaly, dry skinEdemaBleeding gumsPoor wound healingInfection

Can be destroyed by heat and oxygen

Vitamin C deficiency

Summary

Name Form of coezyme

Function Deficiency

Vitamin B1

(thiamine)

TPP coenzyme of oxidative decarboxylation of α–keto acids and transketolase

beriberi

Vitamin B2 (riboflavin)

FMN

FAD

coenzyme of flavin dehydrogenase, transfer of hydrogen

glossitis Cheilosis

Vitamin PP (niacin)

NAD+

NADP+

Coenzyme of dehydrogenase ， transfer of hydrogen

pellagra

Pantothenic acid

CoA Acetyl transfer

Biotin co-enzyme of carboxylase,

carrier of CO2

Summary (continue)

Name Form of coezyme

Function Deficiency

Vitamin B6 Pyridoxal-Phosphate(PLP)

Coenzyme of aminotransferase,

amino carrier

Folic acid FH4 (THF) Carrier of one carbon unit

Megaloblastic anemia

Vitamin B12 Cobalamine,

5 -deoxyadenosylcobalamin

methyl transfer Megaloblastic anemia

Vitamin C ascorbic

acid （ reduce ）hydroxylation scurvy