Download Coenzymes

Lecture 6
Vitamins and Coenzymes
Outline
• Classification of vitamins
• Structure of vitamins
• Features and functions of vitamins
as coenzyme
Introduction
• Some enzymes require cofactors for activity
-- Essential ions
mostly metal ions: Zn2+,Fe2+
-- Coenzymes (organic compounds)
Vitamin-derived coenzymes-derivatives of
vitamins.
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
 Vitamin
 Vitamin
 Vitamin
 Vitamin
 Vitamin

A:
B:
C:
D:
E:
K:
prevent night blindness
anti-beriberi factor
anti-scurvy factor
anti-ricket factor
for reproduce properly
concerned with coagulation
Classification
Water Soluble
 Vitamin C
 B Vitamins
 Thiamine
(B1)
 Riboflavin (B2)
 Niacin
 Pantothenic Acid
 Biotin
 Pyridoxine (B6)
 Folic Acid
 Vitamin B12
(cyanocobalamin)
Lipid Soluble
 Vitamin A
 Vitamin D
 Vitamin E
 Vitamin K
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.
2.
3.
4.
5.
6.
7.
8.
Thiamin (B1)
Riboflavin (B2)
Niacin
Pantothenic Acid
Biotin
Vitamin B6
Folic Acid
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.
Thiazole ring
Thiamine:
named as
the "thiovitamine"
("sulfurcontaining
vitamin")
Pyrimidine ring
Active form :Thiamine pyrophosphate (TPP or cocarboxylase)
N
CH2
H3C
N
+
N
CH3
NH2 HC
CH2
S
Reactive carbon atom
CH2
O
O
O
P O
P
OH
OH
OH
Biochemical function
﹡TPP:
 co-enzyme
of
oxidative
decarboxylation of α–keto acids
and transketolase, involved in
carbohydrate metabolism.
﹡with effects in the
conduction,
inhibiting
cholinesterase activity.
nerve
the
Food Sources of thiamin

Recommended Dietary
Allowance(RDA):
 M:1.2mg/d，



F:1.1mg/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
its name from its color. The root of this word is
the Latin word "flavus" meaning "yellow."
NH2
• Active form (coenzyme):
• flavin mononucleotide (FMN)
N
N
• flavin adenine dinucleotide (FAD)
O
O
H2C
O
HCOH
O
P
OH
P
N
O
CH 3
N
O
OH
HCOH
HCOH
OH
CH 3
N
H3C
Ⅲ
H3C
Ⅱ
N
Ⅰ
N
O
C
C
NH
O
Vit B2
FMN
AMP
FAD
OH
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)
Pyridine derivative
﹡ Vitamin PP
nicotinic acid
nicotinamide
•The name 'niacin' was derived from “nicotinic acid
+ vitamin”
﹡Active form (coenzyme)
Nicotinamide adenine dinucleotide (NAD+)
Nicotinamide adenine dinucleotide phosphate (NADP+)
nicotinamide
adenine
NAD+ (Nicotinamide adenine dinucleotide) , R: H
OH
NADP+ (Nicotinamide adenine dinucleotide phosphate), R:
P
OH
O
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
enriched 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.
pantoic acid
b-alanine
CH 3
HO
CH 2
C
CH
C
CH 3 OH
O
NH
CH 2
CH 2
C
O
OH
Active form :
• coenzyme A (CoA)
• 4-phosphopantetheinyl: acyl carrier protein
(ACP)
Biochemical function
﹡CoA and ACP are coenzyme of acyl transferase，
transfer of acyl.
Pantothenic acid
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 biotindependent enzymes.
• Biotin: co-enzyme of
carboxylase, the
carrier of activated
carbon dioxide(CO2).
Biotin - Food Sources

Widespread in food
 Cheese,
egg yolk, liver, peanut butter,
soybeans, fish

Synthesized by GI (gastrointestinal )
bacteria.
Biotin Defficiency

Deficiency: rare
 Depression
 Numbness（麻痹）
 Lethargy
• Avidin was first
isolated from raw
chicken egg white by
Esmond Emerson Snell
 Dermatitis（皮炎）


Did You Know?
 Eating
large amounts of raw egg white can
lead to biotin deficiency
Raw egg whites contain a glycoprotein
(Avidin) which tightly binds biotin and
prevents its absorption from the intestine;
cooking denatures protein.
6. Vitamin B6 (pyridine derivatives)
﹡Three forms of vitamin B6:

Pyridoxine, pyridoxal, pyridoxamine
﹡Active form :

Pyridoxal-Phosphate(PLP), pyridoxaminePhosphate
Biochemical
function
﹡Coenzyme of amino acid aminotransferase,
decarboxylase, and - amino-- levulinate
synthase （ALA synthase）
Food Sources of Vit B6
• Most protein-rich foods
such as meat, fish, and
poultry provide ample
vitamin B6 ; some
vegetables and fruits
are good sources, too.
Vitamin B6 Deficiency



Overt deficiencies are rare
Isoniazid therapy (the firstline antituberculosis medication)
can induce VitB6 deficiency.
Manifestations




Stomatitis, glossitis
Dermatitis
Irritability, confusion, depression
Anemia
7. Folic acid (or folate)
• 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.
﹡Active form:
Tetrahydrofolate (THF or FH4)
pteridine
para-aminobenzoic acid
(PABA)
FH4 (or THF)
glutamic acid
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 Functions
 New
cell synthesis - GI tract, RBC
 Protein synthesis
 DNA/RNA synthesis
 Increased needs w/ pregnancy

It is especially important during
periods of rapid cell division and
growth.
Folic 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 - Deficiency


Megaloblastic anemia (macrocytic anemia)

An anemia (of macrocytic classification) that
results 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
cause 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.

Dimethylbenzi
midazole(DMB)
Active form:
Methylcobalamin; (R：-CH3)
5 (R：5`-deoxyadenosine)
deoxyadenosylcobalamin
Corrin ring
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
 Shiny
colored skin (anemia/icterus)
tongue (atrophic glossitis)
 Mentally
 Shuffling
sluggish
broad gait
B Vitamins Coenzyme Roles
Vitamin Thiamin
Coenzyme
TPP
Riboflavin
FAD
FMN
Protein Metabolism
Niacin
NAD
B6
NADP
Folate
PLP
Pantothenic
Acid
THF
CoA
Carbohydrate Met
Biotin
PLP
PLP
TPP
FAD
FMN
NADP
THF
B12
B12
NAD
CoA
B12
Biotin
FAD
FMN
CoA
NAD
B12
B12
B12
Fat Metabolism
NAD
ENERGY
Biotin
9. Vitamin C（ascorbic acid）
 Water
soluble
 sour taste (acid)
 Six-carbon polyhydroxy compound
 Strong antioxidant
O
O
1
2
HO
OH
4
3
C
H
OH
CH2OH
O
O
C
HO
HO
H
HO
C
14
O
C
C
O
£«2H
C
OH
Vitamin C
Reduced state
C
O
C
H
C
HO
CH
H2C
£­ 2H
14
O
CH
H2C
OH
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
Vitamin C deficiency

Scurvy
Scaly, dry skin
 Edema
 Bleeding gums
 Poor wound healing
 Infection


Can be destroyed by heat and oxygen
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 ，pellagra
transfer of hydrogen
Pantothenic
acid
CoA
Acetyl transfer
Biotin
co-enzyme of carboxylase,
carrier of CO2
Summary (continue)
Name
Form of
coezyme
Function
Vitamin B6
PyridoxalPhosphate(PLP)
Coenzyme of
aminotransferase,
amino carrier
Folic acid
FH4 (THF)
Carrier of one
carbon unit
Megaloblastic
anemia
Vitamin B12 Cobalamine,
5 deoxyadenosylc
obalamin
methyl transfer
Megaloblastic
anemia
Vitamin C
hydroxylation
scurvy
ascorbic
acid（reduce）
Deficiency