Lec 5 - Cofactors and coenzymes PDF

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Biochemistry Lecture 5...

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8/2/2019

BIO247 Biochemistry Module 1

Lecture 5 Cofactors and Coenzymes

Dr Jason Terpolilli Building 240.3.015 [email protected]

Human metabolism is complex…

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Knowledge of biochemistry will help you avoid failing prey to nutritional fads and food marketing

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Overview 

In the last three lectures, you covered amino acids, proteins and enzymes.

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You’ve looked at enzyme kinetics and touched on how enzyme-catalysed reactions can be regulated.

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In today’s lecture, we’ll look at a suite of molecules essential to enzyme and protein function

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These are Cofactors

What’s a cofactor? 

A cofactor is a small molecule that associates with an enzyme or protein to perform a biochemical reaction.

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You can think of it as an enzyme’s helper.

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Cofactors can be either metals or small organic molecules

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We call the small organic molecules coenzymes

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The key point though is that they are essential to maintaining enzyme or protein function.

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Metal Cofactors 

Metal cofactors are widespread in biology.

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The metals are always in a ionic (charged) state.

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They are positively charged

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They can often occupy more than one stable, charged state

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They are often strongly bound to enzymes or proteins, frequently occupying a space in the catalytic “core” of the molecule

Examples of cofactors Metal

Enzyme or Protein

Role

Fe2+

Cytochromes

ETC

Cu2+

Cytochrome oxidase

ETC

Carbonic anhydrase

Maintain acid-base balance

Mg2+

Hexokinase

Glycolysis

Zn2+

Alcohol dehydrogenase

Oxidises alcohol

Zn2+

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Cytochromes

Coenzymes 

Coenzymes are small organic molecules that associate with enzymes to facilitate biological reactions.

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Coenzymes can be either loosely or firmly bound to an enzyme o o

Tightly bound – prosthetic groups Loosely bound – often function like a cosubstrate

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Vitamins  Importantly, many coenzymes are derived from vitamins.  These are essential molecules required in the human diet.  But, not all organisms need them, as many can synthesise their own  There are 13 essential vitamins, but not all of them function as coenzymes  The major distinction in vitamins is whether they are water or fat soluble

Vitaminsthatactascoenzymes

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Non‐coenzymevitamins

1: Niacin 

Niacin (aka nicotinic acid, nicotinamide or vitamin B3).

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Meat, fish, vegetables, eggs

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Nicotinic acid converted to two very useful coenzymes we will see a lot in the lectures to follow:

o o

Nicotinamide adenine dinucleotide (NAD) Nicotinamide adenine dinucleotide phosphate (NADP)

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Structure of NAD and NADP

ribose

nicotinamide adenine

ribose

Extra phosphate

NAD and NADP 

Oxidation reduction reactions Remember: A molecule is oxidised when it loses electrons A molecule is reduced when it gains electrons

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NAD+ and NADP+ are the oxidised forms

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Both can receive electrons and be reduced

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NADH and NADPH are the reduced forms

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NAD + and NADH

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The mechanism is the same for NADP +

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Cells therefore use NAD and NADP to pick-up or donate electrons in biological reactions

NAD and NADP 

As a substrate molecule undergoes oxidation, it releases 2 hydrogen atoms.

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One hydride ion (H-:) is accepted by the coenzyme, the remaining H+ is absorbed by the cytosol. NAD+ + 2e- + 2H+ NADP+ + 2e - + 2H+

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NADH + H+

NADPH + H+

NAD and NADP associate with dehydrogenases, a type of oxidoreductase (class I)

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Enzyme Classes

NAD and NADP 

NAD and NADP both associate loosely with enzymes

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NAD and NADP can diffuse away from the enzyme into the solvent or to another molecule of enzyme

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They therefore function as water soluble electron carriers.

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NADH is a soluble electron carrier

Glucose NAD+ NADH + H+

Pyruvate

 NADH in cytoplasm from glycolysis travels to mitochondrion

2: Riboflavin 

Vitamin B2

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Cheese, nuts, meat

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Forms part of two coenzymes: o Flavin adenine dinucleotide (FAD) o Flavin adenine mononucleotide (FMN)

 Like NAD, both FAD and FMN participate in redox reactions

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FAD and FMN 

FAD

Riboflavin with an adenine mononucleotide attached 

FMN

Riboflavin with a phosphate attached

FAD and FMN

FAD or FMN

FADH2 or FMNH2

•

The mechanism is the same for FAD and FMN

•

Unlike NAD + and NADP+, both coenzymes accept 2 H + and 2 e -

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FAD and FMN 

As a substrate molecule undergoes oxidation, it releases 2 hydrogen atoms.

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Two H are accepted by the coenzymes,

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FAD + 2e- + 2H+

FADH2

FMN + 2e- + 2H+

FMNH2

FAD and FMN also associate with dehydrogenases, a type of oxidoreductase (class I)

FAD and FMN 

Unlike NAD and NADP, FAD and FMN associate strongly with enzymes and proteins

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Therefore, FAD and FMN form a prosthetic group.

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Are not water soluble electron carriers, but instead often function within electron transport chains

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For example, succinate dehydrogenase (TCA Cycle)

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3. Pantothenate 

Pantothenic acid, vitamin B5

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Mushrooms, cheese, eggs, oil fish

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Very important vitamin which forms part of Coenzyme A (CoASH)

Pantothenate and CoASH

3’-phosphadenosine diphosphate

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CoASH catalyses the transfer of two carbon fragments

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Particularly important in glycolysis and fatty acid metabolism

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4. Thiamine 

Vitamin B1

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Forms coenzyme thiamine pyrophosphate

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Important in reactions where a bond near a C=O is cleaved

5. Pyridoxine 

Vitamin B6

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Forms pyridoxal phosphapte (PLP)

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PLP a prosthetic group of aminotransferases, so very important in amino acid metabolism

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Summary 

Cofactors are important molecules that associate with enzymes and proteins

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Cofactors that are small organic molecules are coenzymes.

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Many coenzymes are derived from vitamins

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Niacin, riboflavin, pantothenate, thiamine and pyridoxine are some vitamins that form coenzymes we will encounter later in the course.

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Understand how NAD(P) and FAD/FMN function as electron acceptors and know the similarities and differences between them

Relevant Textbook References

Ferrier 7th edition

pp 377-398

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