Cofactors and Coenzymes

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Presentation transcript:

Cofactors and Coenzymes Title slide - this section. Cofactors ( an atom or molecule essential for the action of a large molecule, cofactors may include metals or coenzyme) and coenzymes - an organic substances that enhances or is necessary for the action of enzymes.

Cofactors Groups or molecules (other than amino acid residues) which are important to catalysis Metals Coenzymes If tightly bound, it is called a prosthetic group Enzyme without prosthetic group (cofactor) Apoenzyme Enzyme with prosthetic group (cofactor) Holoenzyme Definitions illustrated.

Catalysis by Coenzymes Some common coenzymes Transfers Oxidation/Reduction Nicotinamide Adenine Dinucleotide (NAD+) Flavin Adenine Dinucleotide (FAD) Hydride ion (H-) Electrons Redox coenzymes.

Catalysis by Coenzymes Some common coenzymes One carbon metabolism Biotin Tetrahydrofolate Transfers CO2 One carbon groups Single carbon functional coenzymes.

Catalysis by Coenzymes Some common coenzymes Acyl groups and others Coenzyme A Lipoic acid Thiamine pyrophosphate Pyridoxal phosphate 5’-Deoxyadenosyl-cobalamin Transfers Acyl groups Aldehydes Amino groups and amines Alkyl groups Coenzymes involved in group transfers.

Vitamin Derived Coenzymes Symptoms of vitamin deficiencies

Vitamin Derived Coenzymes Symptoms of vitamin deficiencies.

Examples of Coenzyme Catalysis Uncatalyzed reaction Decarboxylation of an amino acid in an uncatalyzed reaction.

Examples of Coenzyme Catalysis Catalysis with pyridoxal phosphate (Vitamin B6 derivative) The amino acid adds to pyridoxal phosphate to form a Schiff base which is a key intermediate in many transformations. Schiff Base

Examples of Coenzyme Catalysis Electron shifts occur and carbon dioxide is lost.

Examples of Coenzyme Catalysis The amine is released from the coenzyme following more electron shifts.

Examples of Coenzyme Catalysis Nicotinamide adenine dinucleotide and alcohol dehydrogenase NAD+ is reduced producing NADH and in the next slide this reduced form of the coenzyme is used to produce ethyl alcohol. NADH NAD+

Examples of Coenzyme Catalysis Reduction of acetaldelhyde to ethyl alcohol by alcohol dehydrogenase using NADH and H+. . Zn 2+ is a cofactor.

NAD+ reactive site, the yellow R is an H in NAD+ and a phosphate in NADP+

FAD reactive sites

Oxidation of an alcohol to a ketone or aldelhyde

FAD oxidation of a hydrocarbon chain - this kind of reaction occurs in fatty acid oxidation

The oxidized and reduced forms of FAD

Complete reduction of a keto to a CH2

CoA (coenzyme A) is an acyl carrier. The Ac~CoA bond is high energy.

The reactive site on CoA is the -SH

Lipoamide also carrier a H

Think chemistry

Oxidation examples from the Krebs citric acid cycle

ATP is carrying phosporyl groups. Other carrying coenzymes.

Close up of ATP - base in blue, ribose in red, two phosphate in yellow and one in grey.

NADH contains an adenyl group from ATP.

The coenzyme form contains an adenyl group.

CoA also contains an adenyl group with an extra phosphate