1
Enzymes – Part I
Biochemistry I
Lecture 1 2008 (J.S.)
2
Variety of biochemical reactions that comprise life are
remarkable biological catalysts known as enzymes.
As any chemical catalysts at all, enzymes
– remain unchanged after the catalyzed reactions,
– cannot alter reaction equilibria (the values of K),
– increase the rate at which
a reaction approaches
equilibria by lowering the
height of the kinetic barrier,
i.e. by lowering the free
energy of activation ΔG‡
.
3
Nearly all enzymes are proteins.
Some enzymes also have non-protein prosthetic groups
(covalently bound coenzymes), some other enzymes
associate with metal ions or organic coenzymes that are
needed for catalytic activity.
The first enzyme prepared as pure substance in crystalline form was
urease (Sumner 1926), the primary structure of it (complete amino acid
sequence) was recognized in 1960.
Lysozyme was the first enzyme the tertiary structure of which had been
estimated by X-ray diffraction in 1965.
Since the 80´s, some types of ribonucleic acids are known that
catalyze splitting and certain polymerization of nucleic acids.
These catalysts are named ribozymes.
About 3000 different molecular types of enzymes are
present in an average cell. Many of them are localized
only in certain organelles (compartments) within the cell.
The principle of compartmentalization facilitates the
control of different metabolic pathways.
4
The characteristic attributes of enzymes
Enzymes differ from ordinary chemical catalysts
in four important respects:
1 High catalytic efficiency resulting in high reaction rates
2 Enzymes function under mild reaction conditions
3 Specificity of the catalytic action
4 Capacity for regulation
5
1 High catalytic activities
Reaction rates are at least several orders of magnitude greater than
those of the corresponding reactions catalyzed by ordinary chemicals
and 106
–1017
times greater than those of non-catalyzed reaction.
On the other hand, enzymes like other proteins exhibit
a low degree of stability and are subjects of biodegradation.
6
2 Enzymes function under mild reaction conditions:
– at atmospheric pressure,
– at low temperature
(most of the enzymes are denatured above 50 °C),
– in limited range of pH values
(denaturation of enzymes in extremely acidic as
well as alkaline solutions),
– in dilute solutions (at very low enzyme concentrations).
7
3 Enzymes are highly specific catalysts
Specificity in the reaction that enzymes catalyze
An enzymes usually catalyzes a single type of chemical reaction
or a set of closely related reactions
Enzymes are classified on the basis of the types of reactions that they
catalyze (oxidoreductases, transferases, hydrolases, etc.)
The type of catalyzed reaction depends very much of the coenzyme
(if it is needed for the reaction).
Substrate specificity – enzymes are specific in the choice of reactants.
The first step in enzymatic catalysis is the binding of the proper reactant (called
substrate) to the enzyme – the formation of an enzyme-substrate (ES) complex.
From many compounds that may react in a certain type of reaction,
enzymes are usually able to bind
a limited group of similar compounds of the same type.
The existence of a unique specific substrate
(so-called absolute substrate specificity) is rather exceptional.
8
SERINE PROTEASES
Serine 195
Chymotrypsin, trypsin
CYSTEINE PROTEINASES
Carboxypeptidase A, thermolysin (bacterial)
METALLOPROTEINASES
Cathepsins, papain
ASPARTYL PROTEINASES
Pepsin, renin
Example:
Major classes of proteinases
All of them are peptide-cleaving
enzymes.
Due to the different arrangement
of active sites, they exhibit
different substrate specificities
and different catalytic mechanisms.
9
A deep, relatively
hydrophobic pocket
At the bottom of the
deep pocket there is
an acidic residue (Asp)
Two residues of valine
close off the mouth of the
small hydrophobic pocket
The active sites of three homologous serine proteinases
- members of the chymotrypsin family:
Their overall structure is nearly the same, the amino acid sequences are approximately 40 %
identical.
Certain residues other than serine in "additional pockets" play key roles in
determining the substrate specificity of these enzymes.
The peptide bonds preferred to be cleaved
by chymotrypsin are those just past residues with large, hydrophobic, and
uncharged side chains (e.g. Phe, Trp),
by trypsin those after residues with long, positively charged side chains (Arg, Lys),
by elastase those past residues with small hydrophobic side chains (Gly, Ala).
10
Enzymes are frequently stereospecific catalysts
If the reactant of an enzymatic reaction is a chiral compound, only
one of the two enantiomers is recognized as the specific substrate.
R R
X
x
Proper substrate Not-fitting enantiomer
Chiral substrates are bound to the stereospecific enzymes at three
sites:
11
L-Lactate
C
COOH
CH3
HHO
H
C C
CH3
O
O
HO
Enzyme
Example:
When pyruvate is hydrogenated without any catalyst (e.g. in vitro), the
reaction product is the racemic mixture of D-lactate and L-lactate.
In the same reaction catalyzed by lactate dehydrogenase (in the
presence of NADH), pyruvate is reduced stereospecifically to
L-lactate only:
H
C C
CH3
O
O
HO
H
C
COOH
CH3
HHO + C
COOH
CH3
OHH
L-laktát + D-laktátL-Lactate D-Lactate
12
4 Enzymes are regulated catalysts
• The catalytic activity of enzymes can be inhibited or increased
by the binding of specific small molecules and ions,
by the binding of regulatory proteins,
by covalent modifications of enzyme molecules
(e.g. through phosphorylation controlled by extracellular signals).
• The specificity of few enzymes also can be changed
(the specificity of galactosyl transferase during period of lactation)
• The amount of the enzyme in cells is controlled by
induced expression of the particular genes ("adaptable" enzymes),
control of the proteosynthesis of new enzyme molecules
and/or by regulated proteolysis (breakdown) of enzymes.
13
Enzyme nomenclature
Some historical names are used for few enzymes till this time
(without any respect to the function belonging to them, e.g. pepsin,
trypsin, cathepsin, catalase).
The common ending –ase was settled for all enzymes later on.
The contemporary enzyme nomenclature is determined by the
Enzyme Commission (EC) of the International Union of
Biochemistry (IUB).
There are two types of names:
– Systematic names identifying the enzymes fully (with
the enzyme code number, too) without ambiguity. Those names
are not very convenient for everyday use. Only some examples
will be introduced to the students.
– Recommended names (some of them are historical)
are shorter than systematic names; recommended names will be
used in this course.
14
Enzyme nomenclature was adapted according to the
IUB Enzyme classification.
Six major classes of enzymes were constituted:
15
Major class 1 Oxidoreductases
catalyze oxidation-reduction of substrates.
Subclasses and frequent recommended names:
– dehydrogenases catalyze transfers of two hydrogen atoms,
– oxygenases catalyze incorporation of one or two atoms of
oxygen into the substrate (monooxygenases, dioxygenases),
– oxidases catalyze transfers of electrons between substrates
(e.g. cytochrome c oxidase, ferroxidase),
– peroxidases catalyze breakdown of peroxides.
Example: ethanol + NAD+ acetaldehyde + NADH + H+
Recommended name of the enzyme alcohol dehydrogenase
Systematic name ethanol:NAD+
oxidoreductase
(Classification number EC 1.1.1.1 )
16
Major class 2 Transferases
catalyze transfers of an atomic group from one to another substrate.
Subclasses and frequent recommended names:
– aminotransferases, methyltransferases, glucosyltransferases,
– phosphomutases catalysing transfers of the groups PO3
2–
within
certain molecules,
– kinases phosphorylating substrates by the transfer of the
phosphoryl group PO3
2–
from ATP (e.g. hexokinases,
proteinkinases, pyruvate kinase).
Example: glucose + ATP glucose 6-phosphate + ADP
Recommended name of the enzyme glucokinase
Systematic name ATP:D-glucose phosphotransferase
(Classification number EC 2.7.1.1 )
17
Example: glucose 6-phosphate + H2O glucose + HPO4
2–
Recommended name of the enzyme glucose 6-phosphatase
Systematic name glucose 6-phosphate phosphohydrolase
Major class 3 Hydrolases
catalyze hydrolytic splitting of esters, glycosides, ethers, amides and
peptides, anhydrides of acids, etc.
Some subclasses and frequent recommended names:
– esterases (e.g. lipases, phospholipases, ribonucleases,
phosphatases),
– glycosidases (e.g. saccharase, maltase, amylases),
– proteinases and peptidases (pepsin, trypsin, cathepsins,
dipeptidases, carboxypeptidases and aminopeptidases),
– amidases (glutaminase, asparaginase),
– ATPases splitting anhydride bonds of ATP.
18
Major class 4 Lyases
catalyze non-hydrolytic splitting or forming of bonds C–C, C–O,
C–N, C–S through removing (or adding) a small molecule like H2O,
CO2, NH3.
Some frequent recommended names:
– ammonia lyases (e.g. histidine ammonia lyase – histidase),
– decarboxylases (carboxy lyases),
– aldolases (catalyzing aldol cleavage and formation),
– (de)hydratases (carbonate dehydratase, enolase),
– synthases (citrate synthase).
Example: fumarate + H2O L-malate
Recommended name of the enzyme fumarate hydratase
+ H2O
COOH
C H
CH2
HO
COOH
C
C
COOHH
HOOC H
19
Major class 5 Isomerases
catalyze intramolecular rearrangements of atoms.
Frequent names:
– epimerases,
– racemases,
– (some types of) mutases.
Example: UDP-glucose → UDP-galactose
Recommended name UDP-glucose 4-epimerase
20
Major class 6 Ligases
catalyze formation of high-energy bonds C–C, C–O, C–N in the
reaction coupled with hydrolysis of another high-energy
compound (usually molecule ATP).
Frequent recommended names
– carboxylases
– synthetases (e.g. glutamine syntethase; don't change for
synthases in class 4!)
Example: Pyruvate + CO2 + ATP + H2O → oxaloacetate + ADP + Pi
Recommended name pyruvate carboxylase
21
Classification numbers of enzymes
EC (abbr. Enzyme Commission)
major class number
. subclass number
. sub-subclass number
. the enzyme's arbitrarily assigned serial
number in its subsubclass
Example:
Recommended name: Alanine aminotransferase (ALT)
Code number: EC 2.6.1.2
- Major class 2 Transferases
- Subclass 6 - transferring nitrogenous groups
- Sub-subclass 1 - transferring amino groups
- Enzyme's number 2 Alanine aminotransferase
Systematic name: L-Alanine:2-oxoglutarate aminotransferase
22
The structure of enzymes
Not speaking of ribozymes, enzymes are proteins mostly of
globular type. Some of them exhibit simple or complicated
quaternary structures (oligomeric enzymes and multienzyme
complexes).
The catalytic activity of many enzymes depends on the presence of
small molecules – cofactors.
Such an enzyme without its cofactor is referred to as an apoenzyme, the complete
active enzyme is holoenzyme.
Cofactors can be bound to an enzyme covalently as a prosthetic group, or noncovalently
like a "co-substrate" named coenzyme.
Biochemists do not usually discriminate between the two types of cofactors and use
for both the term coenzymes.
Enzymes the structure of which comprises ions or atoms of a metal that function as
cofactors are classified as metalloenzymes.
23
The active sites of enzymes
The active site of an enzyme is a relatively small part of the structure
that binds the substrates (and the cofactor, if any).
It is a three-dimensional cleft formed by groups that come from different
parts of the amino acid sequence.
In the active site there are
– groups that provide the binding of substrates by multiple weak attractions,
– groups that take direct part in the catalytic mechanism (e.g. with an electric
charge or donating protons),
– auxilliary groups that reinforce and finish the proper shape of the active
site (remind the flexibility of protein tertiary structures).
The precisely defined arrangement of atoms in an active site
that is finished after the substrate is bound is the cause of high
substrate specificity of enzymes.
This process of dynamic recognition of the proper substrate(s) is called
induced fit (D. E. Koshland, Jr., 1958).
24
Ribonuclease (from bovine pancreas) – a diagram of the main chain.
The number represent the positions of α-carbons.
The green dots
are the positively charged
residues of Lys and His
that bind negatively charged
chain of the RNA.
The shape of the active
site can be seen as
a deep cut. It enables
binding of the polynucleotide
chain.
25
Lysozyme – The enzyme catalyzes hydrolytic decomposition of
the long chains of the polysaccharide muramic acid
(a constituent of the bacterial cell walls).
The active site again in
the shape of an incision
into the tertiary structure.
Ribbon diagram with
several components of
the active site.
A schematic representation
of the primary structure –
the active site is composed
of residues that come from
different parts of the chain.
26
Enzyme cofactors
Ions or atoms of metals
Coenzymes
Cofactors
27
Numerous coenzymes are derivatives of vitamins:
28
Cofactors of oxidoreductases (Major class 1)
exist in the oxidized and the reduced forms (a redox half-cell).
+
N
H
C
O
NH2
Nicotinic acid
(niacin, PPF)
Nicotinamide
NAD+
- nicotinamide adenine dinucleotideThe
constituent of NAD+
(as well as of NADP+
) is nicotinamide:
O
OH O
N
CONH2
CH2 O P O P O
OH
O O
OH
CH2
H O
OH OH
N
N
N
N
NH2adenine
anhydride bond
+
N
H
C
O
O–
29
NAD+
is the coenzyme of dehydrogenases
It acts as an oxidant that takes off two atoms of hydrogen from the
substrate.
One atom plus one electron (hydride anion H–
) is added to the paraposition
of the pyridinium ring, the remaining H+
binds to the enzyme.
Oxidized form NAD+
(aromatic ring, positive charge)
Reduced form NADH + H+
(quinoid ring, no charge)
Example: Dehydrogenation of ethanol by alcohol dehydrogenase:
30
NADPH + H+
- nicotinamide adenine dinucleotide phosphate
acts as an reductant that supplies two atoms of hydrogen
– to the substrates in reductive syntheses of fatty acids or cholesterol,
– to the hydroxylating enzymatic systems (e.g. synthesis of bile acids
and other steroids, biotransformation of drugs) .
Schematic representation of the hydroxylations
of various biomolecules catalyzed by the hydroxylating monooxygenases:
R-H + O2 + NADPH+H+
→ R-OH + H2O + NADP+
31
FAD - flavin adenine dinucleotide and
FMN - flavin mononucleotide
act as oxidants in certain types catalyzed by dehydrogenases.
Riboflavin (vitamin B2)
a part of coenzymes FAD and FMN
Coenzyme FAD
Oxidized form
N
N N
NH
H3C
H3C
O
O
CH2
CH OH
CH
CH
OH
OH
CH2 O P O
OH
O
P
OH
O
O
CH2
O
OH OH
N
N
N
N
NH2
32
Oxidized forms of coenzymes FAD and FMN také off two atoms of
hydrogen (e.g. from the group –CH2-CH2-).
Example: Dehydrogenation of succinate to fumarate catalysed
by succinate dehydrogenase:
N
N
N
NH
O
O
H3C
N
N
N
N
O
O
H
H+2 H
-2 H
FMN
Oxidized form
FMNH2
Reduced form
H3C
H3C
H3C
CH2–O– P
CH2
H–C–OH
H–C–OH
H–C–OH
CH2–O– P
CH2
H–C–OH
H–C–OH
H–C–OH
COOH
CH2
CH2
COOH
+ FAD
HC
CH
COOH
HOOC
+ FADH2
33
Tetrahydrobiopterin (BH4)
acts as the coenzyme – a reductant – in certain hydroxylations
catalyzed by monooxygenases.
It supplies two atoms of hydrogen and is oxidized to the
quinoid form of dihydropterin:
Molybdopterin
is the derivative of biopterin with the attached heterocycle
that comprises a heteroatom of molybdenum.
It is an important coenzyme of few oxygenases (e.g. xanthine oxidase
and sulfite oxidase).
N
N
N
O
OH
OH
HN
H
H
- 2 H
HN
H
N
N
NHN
O
OH
OH
oxidized (quinoid) form
Dihydrobiopterin
( qBH2 )
reduced form
Tetrahydrobiopterin
( BH4 )
H-NH
34
Lipoic acid - 1,2-dithiolane-3-pentanoic acid, thioctic acid
is a cyclic disulfide attached through an amide bond (lipoamide) to the
transacylase subunit of the 2-oxoacid dehydrogenase complex.
This coenzyme acts as an oxidant: It accepts two hydrogen atoms
from the activated form of an aldehyde, binds the resulting acyl as
a thioester and transfers the acyl onto coenzyme A.
S S
CO–NH–Lys–Enzyme
+ 2 H
S
H
Lipoamide
Oxidized form
Dihydrolipoamide
Reduced form with two sulfanyl groups
CO–NH–Lys–Enzyme
S
H
35
is a substituted 1,4-benzoquinone that acts as the electron acceptor
for flavoprotein dehydrogenases in the respiratory chain.
It has a side chain containing a variable number of (in animals usually 10)
isoprenoid units. Because of its high hydrophobicity, it is entirely dissolved in
the inner mitochondrial membrane.
Ubiquinone (UQ, coenzyme Q)
Ubiquinone accepts stepwise two electrons (from the flavoprotein) and
two protons from the mitochondrial matrix) and is so fully reduced to
ubiquinol:
O
O
CH3
R
H3C-O
OH
•O
+ e–
+ H+
Ubiquinone Semiubiquinone Ubiquinol
OH
OH
+ e–
+ H+
H3C-O
R = –(CH2-CH=C-CH2)10-H
CH3
36
Cytochromes
are haem-containing proteins, which are one-electron carriers due to
reversible oxidation of the iron atom:
N N
NN
Fe 2+
N N
NN
Fe 3+
+ e–
– e–
Mammalian cytochromes are of three types, called a, b, and c.
All these types of cytochromes occur in the mitochondrial respiratory (electron
transport) chain. Cytochromes type b (including cytochromes class P450) occur
also in membranes of endoplasmic reticulum and elsewhere.
37
Iron-sulphur proteins (FeS-proteins, non-haem iron proteins)
are involved in electron transfer in the mitochondrial terminal respiratory chain
or, e.g. in mitochondrial steroid hydroxylations. Despite the different number of iron atoms
present, each cluster accepts or donates only one electron.
Fe2S2 cluster
Fe4S4 cluster
38
Cofactors of other enzymes
In addition to prosthetic groups or coenzymes of oxidoreductases
(carriers of hydrogen atoms and electrons, resp.), there exist many
enzyme cofactors and other molecules able to carry different groups in
activated form. Surprisingly, most interchanges of activated groups
in metabolism are accomplished by a rather small set of carriers
39
Coenzyme A
Acyl groups are important constituents in both catabolism and anabolism.
Coenzyme A serves as carrier of acyl groups. The terminal sulfanyl group (–SH)
in CoA is the reactive site.
After the reaction with ATP and coenzyme A, the acyl group are linked to CoA by
thioester bonds. Acylcoenzymes A carry activated acyl groups.
~
O
OH
CH2OP
O
O
O
O
P O
O
O
N
N
N
N
NH2
HO
P
O
O
OCH2C
HS CH2 CH2 HN
O
C CH2 CH2 HN
O
C CH
CH3
CH3
Cysteamine β-Alanine Pantoic acid
Pantothenic acid
3´-PhosphoADP
Coenzyme A
(abbr. CoA-SH)
40
Lipoic acid (1,2-dithiolane-3-pentanoic acid, thioctic acid)
was mentioned earlier among prosthetic groups of oxidoreductases, as a cyclic
disulfide attached to the transacylase subunit of the 2-oxoacid dehydrogenase
complex (as lipoamide).
It acts both as an oxidant of an activated aldehyde (carried by thiamine
diphosphate), binds the resulting acyl as a thioester and transfers the acyl onto
coenzyme A:
S S
CO–NH–Lys–EnzymeLipoamide
(oxidized form)
S6
-Acyldihydrolipoamide
(reduced form)
S
H
CO–NH–Lys–Enzyme
S
H
S
H
CO–NH–Lys–Enzyme
S
R-CO
– 2 H
R-CH–
OH
CoA-SH
R-CO–S-CoA
Dihydrolipoamide
(reduced form)
41
Thiamin diphosphate (TDP or TPP)
Thiamine diphosphate (TDP) is one of the five cofactors required for the full function
of 2-oxoacid dehydrogenase complex. In the first of the catalysed reaction, it
acts at decarboxylation of the 2-oxoacid (pyruvate, 2-oxoglutarate, branched
chain 2-oxoacid) as a carrier of the resulting activated aldehyde to the
oxidized form of lipoamide.
Thiamine diphosphate serves similarly as the prosthetic group of transketolase
(transfer of activated glycolaldehyde in the pentose phosphate pathway.
Thiamine diphosphate to which activated
acetaldehyde (α-hydroxyethyl group, product
of decarboxylation of pyruvate) is attached
at C-2 of thiazole ring.
Thiamine diphosphate
42
Pyridoxal 5-phosphate (PLP)
N
CH2OH
H3C
HO
CH2OH
N
CH2-O- P
H3C
HO
HC
O The reactive group
Pyridoxine (vitamin B6) Pyridoxal phosphate
Pyridoxal phosphate is the prosthetic group in many enzymes taking part in
α-amino acid metabolism, catalysing the following types of reactions:
- transamination,
- decarboxylation of amino acids,
- cleavage of the bond between α- and β-carbons of serine and threonine or their direct
deamination, etc.
The aldehyde group binds to α-amino group of an amino acid forming an
aldimine (Schiff's base) intermediate so that any of the bonds from the
α-carbon of the amino acid may be labilized.
Details of aminotransferase reaction are shown on the next slide.
Transamination is the example of a "ping-pong“ mechanism, in which the first product
leaves before the second substrate binds, with the prosthetic group of the enzyme
temporarily in an altered form.
43
Transamination
Aldimine of PLP Aldimine of AA
(Schiff's bases)
Amino acid
CH
NH2
COOHR R C–COOH
CH2
N
R CH COOH
CH
N
– H2O + H2O
Oxoacid
R C–
O
COOH
CH2 NH2
Pyridoxamine phosphate
HC=O
Pyridoxal phosphate
1st
half
The sum of these partial reactions:
HOOC–C–CH2-CH2-COOH
O
2-Oxoglutarate
CH2 NH2
Pyridoxamine phosphate
– H2O + H2O HC=O
Pyridoxal phosphate
Glutamate
NH2
HOOC-CH-CH2-CH2-COOH
2nd
half
44
Biotin
Biotin is the prosthetic group of many carboxylases. It is attached to the
apoenzymes by an amide link between its carboxyl and the ε-amino group
of a lysine residue.
After carboxylation, carboxybiotin serves as carrier of activated carboxyl group.
Carboxybiotin
O
N NH
S CO–NH-Lys-E
C–
O
HO
Biotin
O
HN NH
S CO–NH-Lys-E
Pi
HOOC-O–PO3
2–
Carboxyphosphate
HCO3
–
+ ATP
ADP
Carboxybiotin is able to transfer CO2 to acceptors without the input of additional
free energy. Example – mitochondrial pyruvate carboxylase:
CO2-biotin-enzyme + pyruvate biotin-enzyme + oxaloacetate
45
Important recommendation:
Pay attention to the distinguishing of decarboxylations and carboxylations.
Decarboxylations of acids may be
– spontaneous (not catalysed by enzymes),
– catalysed by decarboxylases, e.g.
decarboxylation of amino acids (coenzyme pyridoxal phosphate),
oxidative decarboxylation of pyruvate and other α-ketoacids
(coenzyme thiamine diphosphate).
Carboxylations require the presence of carboxybiotin as donor of CO2, e.g.
carboxylation of pyruvate to oxaloacetate (gluconeogenesis),
carboxylation of acetyl-CoA to malonyl-CoA (synthesis of fatty acids),
carboxylation of propionyl-CoA to methylmalonyl-CoA,
carboxylations in the branched-chain amino acid breakdown.
46
Tetrahydrofolate
(H4folate, FH4, tetrahydropteroylglutamate)
Sites for bonding of one-carbon units
–CO–NH-CH-CH2-CH2-COOH
COOH
105N
N
N
N
H2N
OH
CH2-NH–
H
H
Substituted tetrahydropteridine p-Aminobenzoate
Tetrahydropteroic acid
n Glutamate
(n = 1 – 5)
carries activated one-carbon units. Mammals can synthesize the pteridine
ring, but they are unable to conjugate it to the other two units. They obtain FH4
from their diets or from microorganisms in their intestinal tracts,
The transferred one-carbon units can exist in three oxidation states.
The fully oxidized unit is CO2, but it is carried by biotin rather than by FH4.
47
One-carbon groups transferred by H4folate
Tetrahydrofolate (FH4) N5
,N10
-Methylene FH4 N10
-Hydroxymethyl FH4
N5
-Methyl FH4
N10
-Formyl FH4 N5
,N10
-Methenyl FH4 N5
-Formimino FH4
48
Coenzyme B12
(cobamide cofactors 5´-deoxyadenosylcobalamin, methylcobalamin)
In mammals, only two reactions are known to require coenzyme B12:
- intramolecular rearrangement of methylmalonyl-CoA into succinyl-CoA,
- formation of methionine by remethylation of homocysteine.
N N
NN
Co
+
CH3
N
N
Methylcobalamin
(part of the molecule)
5´-Deoxyadenosylcobalamin