KIMIA KOFAKTOR

DAN KOENZIM
1. PENTRANSFER FOSFAT
2. PENTRANSFER HIDROGEN
3. PENTRANSFER ASIL ATAU METIL
4. PENTRANSFER GG KARBOKSIL
5. PENTRANSFER GG ALDEHID
6. TERLIBAT DLM METABOLISME AS.AMINO

11/04/21 Mas Tono 1

 KOFAKTOR
1. SENYAWA-2 YANG DIPERLUKAN ENZIM
UNTUK MELAKUKAN TRANSFORMASI
2. APOENZIM: MOLEKUL ENZIM TANPA
KOFAKTOR.
3. HOLOENZIM: SPESI AKTIF YG TERBUAT
DR APOENZIM DAN KOFAKTOR.
4. KOFAKTOR DPT BERUPA ION LOGAM
ATAU MOLEKUL ORGANIK YG DIKENAL
DG KOENZIM.

11/04/21 Mas Tono 2

 KOFAKTOR DAN KOENZIM
1. ION LOGAM: Zn2+, Mg2+, Co2+
2. KOENZIM: MOLEKUL ORGANIK KECIL
BUKAN PEPTIDA SERING DISEBUT GUGUS
PROSTETIK.
3. VITAMIN A: MOLEKUL ORGANIK KECIL YG
HARUS ADA DLM MAKANAN.
4. KEBANYAKAN KOENZIM DILIBATKAN DLM
MENGKATALISIS REAKSI-2 METABOLIK.

11/04/21 Mas Tono 3

 PENGGOLONGAN KOENZIM:

1. PEMINDAH FOSFAT.
2. PEMINDAH HIDROGEN.
3. PEMINDAH GG ASIL DAN METIL.
4. PEMINDAH GG KARBOKSIL.
5. PEMINDAH GG ALDEHID.
6. METABOLISME ASAM-2 AMINO.
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 1. Phosphorylating Coenzymes
 Adenosine Triphosphate (ATP)
 ATP carries activated phosphate
 Require magnesium to be active

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 ADENOSIN TRIFOSFAT (ATP)

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 ATP provides the driving force for reactions by
supplying a good leaving group for C-C bond
formation or elimination reactions.

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 2. Coenzymes that Catalyse Hydrogen
Transfer
 Nicotinamide Coenzymes
 Nicotinamide adenine dinucleotide, NAD+ is
a dinucleotide made up of an adenosine
residue and a nicotinamide nucleoside joined
by two phosphate units.
 The nicotinamide ring is the functional part
of the molecule.
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 NIKOTIANAMIDA ADENIN
DINUKLEOTIDA (NAD+)
BAG. AKTIF

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 ILUSTRASI PENGIKATAN H

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The two nicotinamide coenzymes have a very important
role in metabolism and are involved in hundreds of
enzyme catalysed reactions.

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 Mechanism of Hydrogen Transfer

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 Flavin Coenzymes

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 ACTIVE SITE FAD AND FMP

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 Role in Metabolism

Like the nicotinamides the flavin coenzymes are involved

in hydrogen transfer.
The most important aspect of this is the ability to
transfer hydrogen to oxygen as part of respiration.
In other words they utilise molecular oxygen
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 3. Acyl Transfer Coenzymes
ACTIVE
SITE

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 Chemistry of Thiol Esters
• The pKa of the thiol in CoA-SH is ~ 10 (ROH ~ 16) so
at physiological pH reasonable amounts of CoA-S-
can be formed which is a potent nucleophile and more
nucleophilic than RO-.
• Thiol esters (CoA-SAc) are more reactive than esters
as:
– RS- is a much better leaving group than RO-.
– In thiol esters the d-orbitals of S do not overlap
with the p-orbitals. Therefore there is no
mesomeric effect which makes the carbonyl more
polar than in esters.
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 ACYL TRANSFERS MECHANISM

As such acetyl CoA is involved in Claisen condensations.

This is the basis of fatty acid, polyketide (phenol),
terpene and steroid biosynthesis.

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 4. Methylating Coenzymes
ACTIVE SITE

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 MECHANISM OF METHYLATION

S-Adenosylmethionine is the principle methylation agent

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5. Coenzymes that Transfer Carboxyl Groups

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CARBOXYLATION MECHANISM
• Biotin is an essential coenzyme that catalyses the transfer
of carboxyl groups.
– Initially the biotin is anchored to a lysine residue on the
enzyme via the carboxylic acid group.
– This then allows the addition of CO2 to N(1) position of
biotin.

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 Types of Reactions
1. Direct carboxylation of the substrate

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 (2). Transcarboxylation

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 6. Aldehyde transfer coenzyme
Thiamine Pyrophosphate:
• Thiamine pyrophosphate, TPP, is a coenzyme that stabilises
carbanions and in doing so facilitates a number of crucial
reactions.
• It is introduced to the body as thiamine, vitamin B1.
• This then is phosphorylated to produce the active coenzyme.
• TPP catalyses the following reactions of -keto acids. (-
keto acids are produced by pyridoxal phosphate see next
section)
– Non-oxidative decarboxylation
– Oxidative carboxylation
– Acyloin formation
– Transketolisation

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 Thiamine Pyrophosphate (TPP)
ACTIVE SITE

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Chemistry of the Thiazolium Cations

• The active portion of the TPP is the

thiazolium cation.
• This can lose the acidic proton to form a ylid.
• The quaternary ammonium stabilises the
negative charge of the carbanion due to:
– The adjacent positive charge.
– The ability of the d-orbitals of sulfur to accept
some of the negative charge.

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 FORMATION OF YLID

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 Mode of Action

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 7. Coenzymes that stabilise carbanions -
Electrophilic catalysis

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 Mode of action

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 C-H Bond Cleavage

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 Racemisation

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 Transamination

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 The pyridoxal phosphate can be
regenerated

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