07 - Chemistry of Coenzymes

Metallo-enzyme

These are tighly-bound cofactors of enzymes

Ion activator

These are loosely-bound cofactors of enzymes

Prosthetic group

These are tighly-bound coenzymes of enzymes

Second Substrate

These are loosely-bound coenzymes of enzymes

F; They are heat stable
T
F; They accelerate enzymatic reactions
T

MTF: The following are characteristics of coenzymes

1.) Heat-labile
2.) Low Molecular Weight
3.) Inhibit enzymatic reactions
4.) Recover original state at the end of the reaction

Accepting and transferring functional groups

How do coenzymes accelerate enzymatic reactions

Water-soluble vitamins

What type of vitamins are coenzymes derived from?

Ubiquinone, tetrahydrobiopterin, Lipoic Acid

These are the 3 coenzymes not derived from a vitamin

Niacin (B3)

NAD+ and NADP+ are derived from what vitamin?

Riboflavin (B2)

FAD and FMN are derived from what vitamin?

Pantothenic Acid (B5)

What vitamin is CoA derived from?

Thiamine (B1)

What vitamin is TPP derived from?

Pyridoxine (B6)

What vitamin is Pyridoxal Phosphate derived from?

Folic Acid (B9)

What vitamin is THF derived from?

Cyanocobalamin (B12)

What vitamin is Cobamide derived from?

NAD/NADP, FAD/FMN, Ubiquinone, Tetrahydrobiopterin

These 4 coenzymes are involved in redox reactions

Lipoic Acid, TPP, and CoA

These 3 coenzymes are involved in the transfer of acyl groups or active aldehydes

Pyridoxal Phosphate

This coenzyme is involved in amino group transfer

THF

This coenzyme is involved in one carbon compound transfer

Cobamide

This coenzyme is involved in the transfer of alkyl groups

Nitrogenous base, a sugar, and a phosphate

A nucleotide is composed of what 3 parts?

Ribose

What sugar is found in RNA

Deoxyribose

What sugar is found in DNA

Phophodiester bonds

This type of bond links nucleotides together

Adenine and Guanine

Purine bases are found in which nucleotides

Cytosine, Uracil, and Thymine

Pyrimidine bases are found in which nucleotides

F; Thymine is the methylated form of uracil

T/F: Uracil is a methylated form of thymine

AMP and Nicotinamide

What 2 major structures make up NAD+

T

T/F: Nicotinamide is not a true nucleotide which makes NAD+ a pseudonucleotide

2’ hydroxyl group

Which part of AMP in NAD+ may be phosphorylated?

Carbon 4

This is the active site of the nicotinamide group in NAD+

Lactate Dehydrogenase and Malate Dehydrogenase

What 2 enzymes make use of NAD

Glucose-6-Phosphate-Dehydrogenase

What enzyme makes use of NADP

Hydride ion

This is the only molecule that C4 of nicotinamide group of NAD can accept

NADH + H

This is the reduced form of NAD+

Conversion of Lactate → Pyruvate

Lactate dehydrogenase, along with NAD, will catalyze what reaction?

Yes

Can the conversion of lactate to pyruvate be reversed?

Oxidation

When lactate transfers 2 hydrogen to NAD to become pyruvate, does it undergo oxidation or reduction?

260 nm

Peak absorption wavelength of NAD

340 nm

Peak absorption wavelength of NADH

AMP and Isoalloxazine ring (Pseudonucleotide)

What are the 2 structures that make up FAD

Ribitol

What sugar is found in the isoalloxazine ring of FAD

N1 and N5 of isoalloxazine ring

These are the active sites of FAD

Succinate dehydrogenase via histidine residue

FAD is covalently bound to what enzyme via what amino acid residue

Citric Acid Cycle and Complex II of ETC

FAD is a coenzyme for Succinate Dehydrogenase in what pathway

Beta oxidation of fats

FAD is a coenzyme for Acyl CoA Dehydrogenase in what pathway

L-amino acid oxidase (Oxidative Deamination)

FMN is a coenzyme for what enzyme and what pathway?

AMP

What component of FAD is missing in FMN?

Semiquinone Radical

This is the semi-reduced form of FAD and FMN

FADH2

This is the final reduced form of FAD

FMNH2

This is the final reduced form of FMN

2

How many protons/electrons does it take to fully reduce FAD and FMN?

450 nm

Max absorbance wavelength of FAD

Oxidation of succinic acid to fumaric acid

Succinate dehydrogenase, along with FAD, will catalyze what reaction?

C2 and C3

From which carbons will the 2 hydrogen atoms be taken from when succinic acid is oxidized to fumaric acid?

Ubiquinone (CoQ)

This is the lipid soluble coenzyme of the ETC

Benzoquinone ring and repeating isoprenoid units

2 components of CoQ

C1 and C4 of benzoquinone ring

Active site of CoQ

Complex I/II to III

CoQ shuttles electrons between which complexes of the ETC

NADH-CoQ Dehydrogenase

CoQ is a coenzyme in what enzyme in complex I of ETC

Succinate-CoQ Dehydrogenase

CoQ is a coenzyme in what enzyme in complex II of ETC

270-290 nm

Max absorbance wavelength of ubiquinone

Biopterin

Tetrahydrobiopterin is synthesized from what molecule?

Guanosine Triphosphate

Biopterin is synthesized from what molecule?

Hydroxylation of aromatic amino acids

Tetrahydrobiopterin is involved in what type of reactions

Phenylalanine, Tyrosine, and Tryptophan

What amino acids does tetrahydrobiopterin act on?

Phenylalanine Hydroxylase

This enzyme, along with tetrahydrobiopterin, hydroxylates Phe to Tyr

Tryptophan Hydroxylase

This enzyme, along with tetrahydrobiopterin, hydroxylates Tyr to DOPA

Loss of 2 hydrogens to become dihydrobiopterin

What changes occur to tetrahydrobiopterin during hydroxylation?

NADPH

What can act as a reducing agent to recover tetrahydrobiopterin from dihydrobiopterin

4a-hydroxytetrahydrobiopterin

This is the intermediate formed when tetrahydrobiopterin participates in hydroxylation

Phenylketonuria

This is a condition that occurs with the deficiency in the enzyme phenylalanine hydroxylase and reductase to recover tetrahydrobiopterin

Substituted pyrimidine, Thiazole, and pyrophosphate

3 components of TPP

C2 of the thiazole ring

This is the active site of TPP

Mg++

What ion does TPP need for activity?

Thiaminase in raw fish

What molecule inactivates TPP and what is its source?

Adjacent Sulfur and nitrogen tends to draw electrons from C2

What is the reason why the hydrogen in C2 of the thiazole ring is acidic

Pyruvate decarboxylase reaction

TPP is involved in this reaction which involves the removal of carbon dioxide of pyruvate

Acetaldehyde

What is the final product of pyruvate decarboxylase reaction

Hydroxyl-ethyl TPP

Intermediate of the pyruvate decarboxylase reaction

Magnesium

Cofactor required for Pyruvate decarboxylase reaction

Transketolase reaction

TPP is involved in this reaction where a keto group of xylulose-5-phosphate is transferred to the first carbon of ribose-5-phosphate

Glyceraldehyde-3-Phosphate and Sedoheptulose-7-phosphate

Products of the transketolase reaction

C2

In the transketolase reaction involving TPP, which carbon of X5P does the carbanion get attracted to?

C2 and C3

The bond between which carbons of X5P will weaken and eventually break during the transketolase reaction

C1 (Carbonyl Carbon)

In the transketolase reaction, the carbanion of TPP will attack which carbon of R5P

Pyruvate Dehydrogenase Complex

These are the group of enzymes responsible for the oxidative decarboxylation of pyruvic acid

Acetyl-CoA, CO2, and NADH

3 products of the Pyruvate dehydrogenase reaction

TPP

In the pyruvate dehydrogenase complex, what coenzymes accompany pyruvate dehydrogenase

Lipoic Acid and CoA

In the pyruvate dehydrogenase complex, what coenzymes accompany Dihydrolipoyl Transacetylase

FAD and NAD

In the pyruvate dehydrogenase complex, what coenzymes accompany Dihydrolipoyl Dehydrogenase

epsilon-amino group of lys

Lipoic Acid is bound to the enzyme via what side chain of which amino acid?

Open chain/Reduced

Which form of lipoic acid is able to accept an acyl group?

alpha-ketoglutarate dehydrogenase and pyruvate dehydrogenase complex

What 2 enzymes does Lipoic Acid serve as a coenzyme for?

AMP, Pantothenic Acid, Thioethanolamine

What are the 3 components of CoA

Pantoic Acid and Beta-alanine

What 2 structures make up pantothenic acid in CoA

Terminal thiol group on thioethanolamine

Which is the active site of CoA

Sulfur attached to C6 and C8

Which is the active site of lipoic acid?

Fatty Acyl CoASH Synthase and Pyruvate Dehydrogenase Complex

What 2 enzymes does CoA serve as a coenzyme for?

Palmitoyl-adenylate and PPi

To activate palmitic acid, it will first react with ATP to form what structure and byproduct?