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ch8

Horton • Moran • Scrimgeour • Perry • Rawn

Principles of Biochemistry
Fourth Edition

Chapter 7
Coenzymes and Vitamins

Copyright © 2006 Pearson Prentice Hall, Inc.

 Cofactors

 Cofactors: Are chemical species required by inactive

apoenzymes to convert them to active holoenzymes.
 Are essential portion of active sites of certain enzymes.

Inorganic Organic

K+, Ca++, Mg++ Zn++, Fe+3

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 A. Essential ions (minerals)
 Many minerals required by all organisms are essential
because they are cofactors. They could be divided into:
1) Activator ions: reversibly bound to enzymes and often
participate in binding of substrates or in stimulating
enzymes (eg, Ca++, K+, Mg++…).
2) Metal ions of metalo-enzymes: tightly bound cations,
frequently participate directly in catalytic reactions (eg,
Fe+2 in heme containing proteins and iron-sulfur
clusters, and Zn++ in carbonic anhydrase…).

[Fe-S] clusters

3 Heme
 Mechanism of carbonic anhydrase

 The zinc ion in the active site

promotes the ionization of a
bound water molecule.
 The resulting hydroxide ion
attacks the carbon atom of
carbon dioxide, producing
bicarbonate, which is released
from the enzyme.

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 B. Coenzymes
 Coenzymes: are organic cofactors that act as group-
transfer reagents. They are specific for the chemical
group that they accept and donate.
 Can be divided into:
1) Cosubstrates: are actually substrates in enzyme-
catalyzed reaction. Cosubstrate is altered during reaction
and dissociates from the active site, but the original
structure is regenerated in a subsequent reaction
catalyzed by another enzyme (Recycled repeatedly
within the cell).
2) Prosthetic group: remains bound to the enzyme during
the course of the reaction. May be altered during the
reaction but must return to its original form at the end.
Attached covalently to apoenzyme or tightly by many
noncovalent interactions.
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 Source of coenzymes

 Prokaryotes, protists, fungi, and plants are capable

of synthesizing their coenzymes from simple
precursors.
 Animals have lost the ability to synthesize
coenzymes, and need to consume vitamins as
coenzyme precursors (Vitamins is enzymatically
transformed in the body to their corresponding
coenzymes).

 Vitamin-deficiency can lead to certain diseases

that can be cured or prevented by consuming the
appropriate vitamin.

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( B3 )

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scurvy
 • characterised by diarrhoea,
dermatitis and dementia. If left
untreated, death is the usual

characterised by diarrhoea, dermatitis and

dementia. If left untreated, death is the usual

dermatitis
Pernicious anemia
inability to absorb vitamin B 12.

Blood film acute gastritis

 Beriberi
is caused by a lack of thiamine (vitamin B1).

. Its symptoms include weight loss,

emotional disturbances, impaired
sensory perception (Wernicke's
encephalopathy), weakness and
pain in the limbs, and periods of
irregular heart rate. Edema
(swelling of bodily tissues) is
common
• Two broad classes of vitamins :
• water-soluble (such as B vitamins).Water-soluble
vitamins are required daily in small amounts
because they are readily excreted in the urine and
the cellular stores of their coenzymes are not
stable.
• fat-soluble such as vitamins A, D, E, and K, are
stored by animals and excessive intakes can result
in toxic conditions known as hypervitaminoses.
• It’s important to note that not all vitamins are
coenzymes or their precursors
( B3 )

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Adenosine triphosphate (ATP)
 Reactions of ATP

• ATP is a versatile reactant that can donate its:

(1) Phosphoryl group (g-phosphate)
(2) Pyrophosphoryl group (g,b phosphates)
(3) Adenylyl group (AMP)
(4) Adenosyl group

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Adenosine triphosphate (ATP)

AMP
ADP
ATP
 Adenosine triphosphate (ATP)

• phosphoryl
group transfer.
ATP and S-adenosylmethionine
S-adenosylmethionine
 S-adenosylmethionine
• is the donor of almost all the methyl groups used in
biosynthetic reactions( Methylation reactions).
• For example, it is required for conversion of the hormone
norepinephrine to epinephrine.
 Nucleotide-sugar coenzymes
• The most common nucleotide sugar, uridine
diphosphate glucose (UDP-glucose)
• are involved in carbohydrate metabolism.

The mobile glycosyl group of UDP-glucose is shown

in red
uridine diphosphate glucose
(UDP-glucose
Oxidation-Reduction reaction
NAD+ NADP+
 NAD+ NADP+
• Nicotinamide coenzymes
• Electron transfer during oxidation-reduction reactions.
• Ultraviolet absorption (between oxidized and reduced form).
• NADPH used in biosynthetic reactions.

• Its deficiency cause pellagra

• In many species, tryptophan is degraded to nicotinic acid.
Oxidized and reduced forms of NAD (and NADP)

Nicotinamide adenine dinucleotide

 NAD+ NADP+
• NAD and NADP are a cosubstrate for
dehydrogenases.
• Lactate dehydrogenase is an oxidoreductase that
catalyzes the reversible oxidation of lactate. The
enzyme is a typical NAD-dependent
dehydrogenase.A proton is released from lactate
when NAD is reduced.
FAD FMN
 FAD FMN
• flavin adenine dinucleotide (FAD) and flavin mononucleotide
(FMN) are derived from Riboflavin Vit. B2
• Prosthetic group –tightly bound
• Participate in one e- transfers and two e in two steps

Flavin adenine dinucleotide

Riboflavin Vit. B2

black is FMN, black and blue is FAD

 Coenzyme A

• Panthothenate vit. B5
• Biosynthesis of some carbohydrates & lipids
• Acyl group transfer reactions
• Is a prosthetic group of ACP
Coenzyme A and acyl carrier protein (ACP

(a) In
coenzyme A, 2-mercaptoethylamine is bound to
the vitamin pantothenate, which in turn is bound via a
phosphoester linkage to an ADP group that has an
additional 3'-phosphate group
• Acyl groups covalently attach to the —SH
group to form thioesters.
• A common example is acetyl CoA (where
the acyl group is an acetyl moiety.
• .Acetyl CoA is a “high energy”compound
due to the thioester linkage
 Thiamine pyrophosphate TPP

• coenzyme is thiamine diphosphate (TDP),

also called thiamine pyrophosphate (TPP)
• TDP is synthesized from thiamine by
enzymatic transfer of a pyrophosphoryl
group from ATP
 Thiamine pyrophosphate TPP
TDP is prosthetic group of:
a) Decarboxylase (eg. Pyruvate decarboxylase).
b) Oxidative decarboxylation (eg. Oxidative
carboxylation by pyruvate dehydrogenase in
carbohydrate metabolism,…)
c) Transketolases in the pentose phosphate pathway.
catalyze transfer between sugar molecules of two-carbon
groups that contain a keto group.
 Pyruvate-
dehydrogenase
complexe

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Pyridoxal phosphate
 Pyridoxal phosphate
• Vit. B6
• Prosthetic group for E that catalyze a variety of AA
reactions: isomerizations decarboxylations, side
chain eliminations or replacements.
 Biotin

• prosthetic group for enzymes that catalyze carboxyl group transfer

reactions and ATP-dependent carboxylation reactions (carboxylase
 biotin
• biotin deficiency is rare in humans or animals on
normal diets because biotin is synthesized by
intestinal bacteria and is required only in very small
amounts
• A biotin deficiency can be induced, however, by
ingesting raw egg whites that contain a protein
called avidin. Avidin binds tightly to biotin making
it unavailable for absorption
• Avidin ( can be used in affinity chromatography
Tetrahydrofolate FH4
 Tetrahydrofolate FH4
• FH4
• Polyglutamate form.
• Dihydrofolate reductase thymidylate biosynthesis of DNA
• Transfers of several one-carbon unit
(c)The polyglutamate forms of tetrahydrofolate usually contain five or six
glutamate residues. The reactive centers of the coenzyme, N-5 and N-10, are shown
in red.
One-carbon derivatives of tetrahydrofolate. The
derivatives can be interconverted enzymatically by
the routes shown. (R represents the benzoyl
polyglutamate portion of tetrahydrofolate.)

DNA biosynthesis
Participation of Vit B9 in synthesis of dTMP from dUMP

5-Flouro Uracil

Provides the methyl group for

thymine in DNA
Needed for a pregnant women
Cobalamin vit. B12
- Vitamin B12 (Cobalamin):
Vitamin B12 is required in humans for two
enzymatic reactions:
- Remethylation of homocycteine to methionine
- Isomerization of methylmalonyl CoA
The structure of vitamin B12 contains a corrin
ring system. Cobalt is coordinated in the center of
the ring.
 Cobalamin Coenzymes derived from cobalamin

R= −CN (in cyanocobalamin)

R= −OH (in hydroxocobalamin)
R= H2O (in aquocobalamin)

 Metal coordinated by corrin is cobalt.

 Benzimidazole ribonucleotide (blue) is coordinated with cobalt and is
bound via phosphoester linkage to a side chain of corrin ring system. also
Methylcobalamin participates in the transfer of methyl groups, as
in the regeneration of methionine from homocysteine in
mammals.

In this reaction, the methyl group of 5-methyltetrahydrofolate is

passed to a reactive, reduced form of cobalamin to form
methylcobalamin that can transfer the methyl group to the thiol
side chain of homocysteine.
The coenzyme participates in several enzyme-catalyzed intramolecular
rearrangements in which a hydrogen atom and a second group,bound to adjacent
carbon atoms within a substrate, exchange places

Intramolecular rearrangements catalyzed by adenosylcobalamin-dependent

enzymes. (a) Rearrangement in which a hydrogen atom and a substituent on an
adjacent carbon atom exchange places. (b) Rearrangement of methylmalonyl CoA
to succinyl CoA, catalyzed by methylmalonyl–CoA mutase.
Vitamin B12 human deficiency disease:
- Pernicious anemia.
 ascorbic acid
• ascorbic acid is not a coenzyme but acts as a
reducing agent in several different
enzymatic reactions
• The most important of these reactions is the
hydroxylation of collagen
Ascorbic acid
 Lipid vitamins
• Rings & long aliphatic side chains-
hydrophobic although each possesses at
least one polar group.
• Micelles with bile salts
 - Vitamin A (Retinol):
Vitamin A is often used as a collective term for
several related biologically active molecules:
Retinol, Retinal, Retinoic acid (from animal
foods).
Plant foods contain β-carotene, which can be
oxidatively cleaved to yield two molecules of
retinol.
oxidation
Carotene 2 vit A
α b γ destruction of the double bond in the middle of the chain
CH3 CH3 CH3 CH3
H
CH2OH C
oxidation O

alcohol group aldehyde group

CH3
Vit A
(Retinol) Retinal
 - Vitamin A (Retinol):

-Retinoic acid: regulate gene expression during

cell differentiation.
-Retinal : light sensitive compound, important role
in vision. it is the prothetic group of the protein
rhodopsin.
 - Vitamin D (Cholecalciferol):

• Vitamin D is the collective name for a group of related lipids.

• Vitamin D3 (cholecalciferol) is formed nonenzymatically in the skin
from the steroid 7-dehydrocholesterol when humans are exposed to
sufficient sunlight.
• Vitamin D2, a compound related to vitamin D3 (D2 has an additional
methyl group), is the additive in fortified milk.
• The active form of vitamin D3: is 1,25-dihydroxycholecalciferol
(Calcitriol ) formed from vitamin D3 by two hydroxylation reactions.
• Vitamin D2 is similarly activated
- Vitamin D (Cholecalciferol):

• —vitamin D regulates both intestinal

absorption of calcium and its deposition in
bones.
• In vitamin D– deficiency diseases, such as
rickets in children and osteomalacia in
adults, bones are weak because calcium
phosphate does not properly crystallize on
the collagen matrix of the bones.
Functions of Vit .D
Functions of Vit .D
- Vitamin E (Tocopherol):

• α-tocopherol
• Deficiency : cause Fragile red blood cells
neurological damage.
- Vitamin E (Tocopherol):
• α-tocopherol
• The phenol group of vitamin E can undergo oxidation to a
stable free radical.
• Vitamin E is believed to function as a reducing agent that
scavenges oxygen and free radicals.
• This antioxidant action may prevent damage to fatty acids
in biological membranes.
• A deficiency of vitamin E is rare but may lead to fragile
red blood cells and neurological damage. The deficiency is
almost always caused by genetic defects in absorption of
fat molecules.
- Vitamin K (Phylloquinone):

• Phylloquinone
• is required for the synthesis of some of the
proteins involved in blood coagulation
• Coenzyme for carboxylase
Vitamin K is the coenzyme in the
carboxylation of the γ-carbon of glutamate
side chains in proteins, forming γ-
carboxyglutamate (Gla).
This mechanism is essential for activation of
clotting factors such as: prothrombin
(clotting factor II) and blood clotting
factors II, VII, IX, and X.
The Gla-Ca+2 complex is then able to bind to
phospholipids essential for blood clotting on the
surface of platelets.

Vitamin K human deficiency disease:

- Hypoprothronbinemia.