Enzymes Cofactors 2012

8/22/2019 Enzymes Cofactors 2012

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Enzymes-cofactorsDr. Mamoun Ahram


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Resources

Biochemistry. 5th edition. Berg JM, Tymoczko JL, Stryer L. New

York: W H Freeman; 2002.

8.1.1 Many Enzymes Require Cofactors for Activity

http://www.ncbi.nlm.nih.gov/books/NBK22380/ Section 9.2 Making a Fast Reaction Faster: Carbonic

Anhydrases

http://www.ncbi.nlm.nih.gov/books/NBK22599/

The Medical Biochemistry Pages Introduction to Vitamins and Minerals

http://themedicalbiochemistrypage.org/vitamins.php
http://www.ncbi.nlm.nih.gov/books/NBK22380/http://www.ncbi.nlm.nih.gov/books/NBK22599/http://themedicalbiochemistrypage.org/vitamins.phphttp://themedicalbiochemistrypage.org/vitamins.phphttp://www.ncbi.nlm.nih.gov/books/NBK22599/http://www.ncbi.nlm.nih.gov/books/NBK22599/http://www.ncbi.nlm.nih.gov/books/NBK22599/http://www.ncbi.nlm.nih.gov/books/NBK22380/http://www.ncbi.nlm.nih.gov/books/NBK22380/http://www.ncbi.nlm.nih.gov/books/NBK22380/


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Cofactors

What are cofactors?

What are coenzymes?

When are coenzymes called prosthetic groups and

when are they cosubstrates?


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Classification of cofactors

Cofactors

Metals

Metallo-proteins

Metal-associated

proteins

Small organicmolecules

Coenzymes cosubstrates


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Apoenzymes vs. holoenzymes


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Vitamin derivatives as cofactors

What are vitamins?

Why are they important?

What are the two classes of vitamins?


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Vitamin C

Ascorbic acid

Example: prolyl

hydroxylase

synthesizes 4-hydroxyproline

(collagen)

An antioxidant


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Thiamin (vitamin B1)

Active form: thiamin pyrophosphate, TPP


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Pyruvate dehydrogenase complex

Decarboxylation of pyruvate into acetyl CoA by the

pyruvate dehydrogenase complex


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-ketoglutarate dehydrogenase

Decarboxylation of -ketoglutarate into succinyl CoA

by -ketoglutarate dehydrogenase


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Riboflavin (vitamin B2)

The precursor for the coenzymes flavin adenine

mononucleotide (FMD) and flavin adenine

dinucleotide (FAD)


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Flavoproteins

Protiens that require FMN or FAD as cofactors

Redox reactions

FAD and FMN are prosthetic groups


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Succinate dehydrogenase

Oxidation of succinate into fumarate by succinate

dehydrogenase


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FAD is a prosthetic group for the pyruvate

dehydrogenase complex

It does not change in the overall reaction


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Niacin (vitamin B3)

Precursor of nicotinamide adenine dinucleotide(NAD+) and nicotinamide adenine dinucleotidephosphate (NADP+)

Cofactors for numerous dehydrogenases

Cosubstrates


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Pantothenic acid (vitamin B5)

Precursor of alanine and pantoic acid

Synthesis of coenzyme A (CoA)

Metabolism of carbohydrate, fats and proteins


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Coenzyme A

Coenzyme A transports acetyl groups from one

substrate to another

via reactive thioester bond


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Decarboxylation of pyruvate into acetyl CoA by the

pyruvate dehydrogenase complex


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Citrate synthase

Condensation of acetyl CoA and oxaloacetate into

citrate by citrate synthase


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Pyridoxal phosphate (vitamin B6)

Pyridoxal, pyridoxamine and pyridoxine are

precursors of active form

Metabolism of amino acids

pyridoxal

phosphate

PyridoxaminePyridoxalPyridoxine


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Aminotransferases

All aminotransferases contain the prosthetic group

pyridoxal phosphate (PLP)


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Examples

Aspartate aminotransferase

Alanine aminotransferase


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Biotin

Carboxylation reactions


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Pyruvate carboxylase

condensation of CO2 to pyruvate forming oxaloacetate

by pyruvate carboxylase


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Acetyl CoA carboxylase

Carboxylation of acetyl CoA to malonyl CoA by acetyl

CoA carboxylase initiating fatty acid synthesis

Biotin is a prosthetic group


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Cobalamin (vitamin B12)

Composed of a tetrapyrrol ring

structure and a cobalt ion in the

center

Two significant reactions

linking fatty acid metabolism

to sugar metabolism by

rearranging methylmalonyl

CoA to succinyl CoA

the formation of methionine

from homocysteine by

methylation


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Folic acid

Reduced within cells to tetrahydrofolate (THF) by

dihydrofolate reductase (DHFR), an NADPH-requiring

enzyme

THF derivatives carry and transfer of one carbon unitsduring biosynthetic reactions, especially of nucleotides


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Lipoic acid

Not a dietary requirement in humans

Not a vitamin

A co-factor in pyruvate dehydrogenase and -

ketoglutarate dehydrogenase


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Metals

EnzymeMetalCarbonic anhydraseZn2+CarboxypeptidaseZn2+

HexokinaseMg2+Glutathione peroxidaseSeSuperoxide dismutaseMn2+


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Example


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Documents

Enzymes Cofactors 2012