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KIMIA KOFAKTORKIMIA KOFAKTOR DAN KOENZIM DAN KOENZIM

1.1. PENTRANSFER FOSFATPENTRANSFER FOSFAT

2.2. PENTRANSFER HIDROGENPENTRANSFER HIDROGEN

3.3. PENTRANSFER ASIL ATAU METILPENTRANSFER ASIL ATAU METIL

4.4. PENTRANSFER GG KARBOKSILPENTRANSFER GG KARBOKSIL

5.5. PENTRANSFER GG ALDEHIDPENTRANSFER GG ALDEHID

6.6. TERLIBAT DLM METABOLISME TERLIBAT DLM METABOLISME

AS.AMINOAS.AMINO

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KOFAKTORKOFAKTOR

1.1. SENYAWA-2 YANG DIPERLUKAN SENYAWA-2 YANG DIPERLUKAN ENZIM UNTUK MELAKUKAN ENZIM UNTUK MELAKUKAN TRANSFORMASITRANSFORMASI

2.2. APOENZIM:APOENZIM: MOLEKUL ENZIM MOLEKUL ENZIM TANPA KOFAKTOR.TANPA KOFAKTOR.

3.3. HOLOENZIMHOLOENZIM: SPESI AKTIF YG : SPESI AKTIF YG TERBUAT DR APOENZIM DAN TERBUAT DR APOENZIM DAN KOFAKTOR.KOFAKTOR.

4.4. KOFAKTORKOFAKTOR DPT BERUPA ION DPT BERUPA ION LOGAM ATAU MOLEKUL ORGANIK LOGAM ATAU MOLEKUL ORGANIK YG DIKENAL DG YG DIKENAL DG KOENZIMKOENZIM..

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KOFAKTOR DAN KOFAKTOR DAN KOENZIMKOENZIM

1.1. ION LOGAM: ZnION LOGAM: Zn2+2+, Mg, Mg2+2+, Co, Co2+2+

2.2. KOENZIMKOENZIM: MOLEKUL ORGANIK KECIL : MOLEKUL ORGANIK KECIL

BUKAN PEPTIDA SERING DISEBUT BUKAN PEPTIDA SERING DISEBUT

GUGUS PROSTETIK.GUGUS PROSTETIK.

3.3. VITAMIN AVITAMIN A: MOLEKUL ORGANIK KECIL : MOLEKUL ORGANIK KECIL

YG HARUS ADA DLM MAKANAN.YG HARUS ADA DLM MAKANAN.

4.4. KEBANYAKAN KOENZIM DILIBATKAN KEBANYAKAN KOENZIM DILIBATKAN

DLM MENGKATALISIS REAKSI-2 DLM MENGKATALISIS REAKSI-2

METABOLIK.METABOLIK.

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PENGGOLONGAN PENGGOLONGAN KOENZIM:KOENZIM:

1.1. PEMINDAH FOSFAT.PEMINDAH FOSFAT.

2.2. PEMINDAH HIDROGEN.PEMINDAH HIDROGEN.

3.3. PEMINDAH GG ASIL DAN METIL.PEMINDAH GG ASIL DAN METIL.

4.4. PEMINDAH GG KARBOKSIL.PEMINDAH GG KARBOKSIL.

5.5. PEMINDAH GG ALDEHID.PEMINDAH GG ALDEHID.

6.6. METABOLISME ASAM-2 AMINO.METABOLISME ASAM-2 AMINO.

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1. 1. Phosphorylating Phosphorylating CoenzymesCoenzymes

Adenosine Triphosphate (ATP)Adenosine Triphosphate (ATP) ATP carries activated phosphateATP carries activated phosphate Require magnesium to be activeRequire magnesium to be active

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ADENOSIN TRIFOSFAT ADENOSIN TRIFOSFAT (ATP)(ATP)

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

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2. 2. Coenzymes that Catalyse Coenzymes that Catalyse Hydrogen Transfer Hydrogen Transfer

Nicotinamide CoenzymesNicotinamide Coenzymes

Nicotinamide adenine dinucleotide, Nicotinamide adenine dinucleotide,

NADNAD++ is a dinucleotide made up of an is a dinucleotide made up of an

adenosine residue and a nicotinamide adenosine residue and a nicotinamide

nucleoside joined by two phosphate nucleoside joined by two phosphate

unitsunits..

The nicotinamide ring is the The nicotinamide ring is the

functional part of the moleculefunctional part of the molecule. .

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NIKOTIANAMIDA ADENIN NIKOTIANAMIDA ADENIN DINUKLEOTIDA (NADDINUKLEOTIDA (NAD++))

BAG. BAG. AKTIFAKTIF

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ILUSTRASI ILUSTRASI PENGIKATAN HPENGIKATAN H

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

reactions.reactions.

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Mechanism of Hydrogen Mechanism of Hydrogen TransferTransfer

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Flavin Coenzymes Flavin Coenzymes

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ACTIVE SITE FAD AND ACTIVE SITE FAD AND FMPFMP

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Role in Metabolism Role in Metabolism

Like the nicotinamides the flavin Like the nicotinamides the flavin coenzymes are involved in hydrogen coenzymes are involved in hydrogen transfer. transfer. The most important aspect of this is the The most important aspect of this is the ability to transfer hydrogen to oxygen as ability to transfer hydrogen to oxygen as part of respiration. part of respiration. In other words they utilise molecular In other words they utilise molecular oxygen oxygen

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3. 3. Acyl Transfer Acyl Transfer Coenzymes Coenzymes

ACTIVE ACTIVE SITESITE

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Chemistry of Thiol EstersChemistry of Thiol Esters

• The pKa of the thiol in CoA-SH is ~ 10 (ROH ~ The pKa of the thiol in CoA-SH is ~ 10 (ROH ~ 16) so at physiological pH reasonable amounts 16) so at physiological pH reasonable amounts of CoA-Sof CoA-S-- can be formed which is a potent can be formed which is a potent nucleophile and more nucleophilic than ROnucleophile and more nucleophilic than RO--..

• Thiol esters (CoA-SAc) are more reactive than Thiol esters (CoA-SAc) are more reactive than esters as: esters as: – RSRS-- is a much better leaving group than RO is a much better leaving group than RO--..– In thiol esters the d-orbitals of S do not In thiol esters the d-orbitals of S do not

overlap with the p-orbitals. Therefore there overlap with the p-orbitals. Therefore there is no mesomeric effect which makes the is no mesomeric effect which makes the carbonyl more polar than in esters. carbonyl more polar than in esters.

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ACYL TRANSFERS ACYL TRANSFERS MECHANISMMECHANISM

As such acetyl CoA is involved in Claisen As such acetyl CoA is involved in Claisen condensations. condensations.

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

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4.4. Methylating Methylating CoenzymesCoenzymes

ACTIVE ACTIVE SITESITE

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MECHANISM OF MECHANISM OF METHYLATIONMETHYLATION

S-Adenosylmethionine is the principle S-Adenosylmethionine is the principle methylation agent methylation agent

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5. Coenzymes that Transfer 5. Coenzymes that Transfer Carboxyl GroupsCarboxyl Groups

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CARBOXYLATION CARBOXYLATION MECHANISMMECHANISM

• Biotin is an essential coenzyme that Biotin is an essential coenzyme that catalyses the transfer of carboxyl groups. catalyses the transfer of carboxyl groups. – Initially the biotin is anchored to a lysine Initially the biotin is anchored to a lysine

residue on the enzyme via the carboxylic residue on the enzyme via the carboxylic acid group. acid group.

– This then allows the addition of COThis then allows the addition of CO22 to to N(1) position of biotin. N(1) position of biotin.

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Types of ReactionsTypes of Reactions1. 1. Direct carboxylation of the Direct carboxylation of the

substratesubstrate

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(2). (2). TranscarboxylationTranscarboxylation

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6.6. Aldehyde transfer Aldehyde transfer coenzymecoenzymeThiamine PyrophosphateThiamine Pyrophosphate::

• Thiamine pyrophosphate, TPP, is a coenzyme Thiamine pyrophosphate, TPP, is a coenzyme that stabilises carbanions and in doing so that stabilises carbanions and in doing so facilitates a number of crucial reactions. facilitates a number of crucial reactions.

• It is introduced to the body as thiamine, It is introduced to the body as thiamine, vitamin B1. vitamin B1.

• This then is phosphorylated to produce the This then is phosphorylated to produce the active coenzyme. active coenzyme.

• TPP catalyses the following reactions of TPP catalyses the following reactions of --keto acids. (keto acids. (-keto acids are produced by -keto acids are produced by pyridoxal phosphate see next section) pyridoxal phosphate see next section) – Non-oxidative decarboxylationNon-oxidative decarboxylation– Oxidative carboxylationOxidative carboxylation– Acyloin formationAcyloin formation– Transketolisation Transketolisation

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Thiamine PyrophosphateThiamine Pyrophosphate (TPP)(TPP)

ACTIVE ACTIVE SITESITE

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Chemistry of the Chemistry of the Thiazolium CationsThiazolium Cations

• The active portion of the TPP is the The active portion of the TPP is the thiazolium cation.thiazolium cation.

• This can lose the acidic proton to form This can lose the acidic proton to form a ylid. a ylid.

• The quaternary ammonium stabilises The quaternary ammonium stabilises the negative charge of the carbanion the negative charge of the carbanion due to: due to: – The adjacent positive charge.The adjacent positive charge.– The ability of the d-orbitals of sulfur to The ability of the d-orbitals of sulfur to

accept some of the negative charge. accept some of the negative charge.

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FORMATION OF YLIDFORMATION OF YLID

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Mode of Action Mode of Action

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77. Coenzymes that stabilise . Coenzymes that stabilise carbanions - Electrophilic catalysiscarbanions - Electrophilic catalysis

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Mode of action Mode of action

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CC-H Bond Cleavage-H Bond Cleavage

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Racemisation Racemisation

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Transamination Transamination

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The pyridoxal phosphate The pyridoxal phosphate can be regenerated can be regenerated