Coenzymes and cofactors activity in enzymes Many Enzymes

Co-enzymes and cofactors activity in enzymes

Many Enzymes Require Cofactors for Activity A cofactor is a small non-protein molecules that is bound (either tightly or loosely) to an enzyme and is required for catalysis. Catalytic activity of many enzymes depends on the presence of cofactors.

Many Enzymes Require Cofactors for Activity

Types of cofactors 4

Essential Ion Cofactors Activator ions – bind reversibly to enzyme and often participate in substrate binding. Metal ions of metalloenzymes – cations that are tightly bound to enzyme and participate directly in catalysis (Fe, Zn, Cu, Co). Metal activated enzymes – require or are stimulated by addition of metal ions (i. e. Mg 2+, is required by many ATP requiring enzymes)

inorganic cofactors Functions of iron Iron must be present in hemoglobin in order to pick oxygen • Electron transport • Oxygen binding • Oxygen carrier

Examples of Iron-dependent Enzymes Aldehyde Oxidase R-CHO + O 2 RCOOH + H-O-O-H Tryptophan 5 -monooxygenase L-tyrptophan + BH 4 + O 2 5 OH L-tryptophan + BH 2 + H 2 O Fatty Acid desaturase Stearoyl-Co. A + NADH + H+ + O 2 Oleoyl-Co. A + NAD+ + 2 H 2 O Peroxidase 2 H 2 O 2 2 H 2 O + O 2 (O 2 is either incorporated into the product or reduced by electrons)

Inorganic cofactors Mg 2 is used in glycolysis. In the first step of converting glucose to glucose 6 phosphate

Zinc Function 300 enzymes require zinc ◦ DNA, RNA polymerases numerous hormones require zinc ◦ insulin transcription factors (zinc finger proteins) membrane stability myelination skeletal development

Example of prosthetic group Metalloenzymes contain firmly bound metal ions at the enzyme active sites (examples: iron, zinc, copper, cobalt). Example of metalloenzyme: carbonic anhydrase contains zinc

Ion Examples of enzymes containing this ion Cupric Cytochrome oxidase Ferrous or Ferric Cytochrome (via Heme) Hydrogenase Magnesium Glucose 6 -phosphatase Hexokinase Manganese Arginase Molybdenum Nitrate reductase Nitrogenase Nickel Urease Zinc Alcohol dehydrogenase Carbonic anhydrase

Coenzymes are small organic non-protein molecules. Loosely attached to apoenzymes, seperated easily by dialysis they are often called cosubstrate or secondary substrate. Reaction involving: oxidoreduction, group. transfer, Isomerization and covalent bond formation req. coenzyme.

Coenzymes • Organic molecule that temporarily binds to apoenzyme in order for it to work + apoenzyme Protein coenzyme Non-Protein holoenzyme Total

The functional role of Coenzymes is to act as transporters of chemical group A coenzyme is a necessary helper for enzymes that assist in biochemical transformations. These molecules act to transfer chemical groups between enzymes or from Enzyme to substrate or product. A coenzyme Transport a variety of chemical groups (Such as Hydride, Acetyl, Formyl, Methenyl or methyl).

Vitamin Insufficiency Generally Result in malfunction of enzymes Main clinical symptoms of dietary vitamin insufficiency generally arise due the malfunction of enzymes. Dietary vitamin insufficiency leads to a lack of sufficient cofactors derived from vitamins to maintain homeostasis.

Vitamins of B complex group acting as co-enzymes vitamins Thiamine Vitamin B 1 active form (co-enzyme) TPP (thiamine pyrophosphate) Riboflavin Vitamin B 2 FMN, FAD Niacin Vitamin B 3 NAD, NADH Pantothenic acid Vitamin component of coenzyme B 5 A Pyridoxine Vitamin B 6 PLP (pyridoxal phosphate) Biotin Folic acid THF Cobalamine Vitamin B 12 cobamide (Tetrahydrofolate)

Vitamin B 1 - Thiamine q The active form is thiamin pyrophosphate (TPP) § Thiamin is rapidly converted to thiamin pyrophosphate (TPP) in small intestine, brain and liver. § TPP is formed from thiamin by the action of thiamine diphosphotransferase. q TPP coenzyme is required by enzymes in the decarboxylation of -keto acids. q Entity Transferred; Aldehydes

TPP as co-enzymes

Riboflavin functions, vit B 2 Active forms are ◦ Flavin adenine dinucleotide (FAD) ◦ Flavin mononucleotide (FMN) These play key roles in hydrogen transfer reactions associated with ◦ Glycolysis ◦ TCA cycle ◦ Oxidative phosphorylation. 21

Regulated by ACTH, aldosterone, and thyroid hormone p. 283 b

p. 283 c

FAD As co-enzyme

Vitamins and Derivatives Involved in Group Transfer Reactions Nicotine Adenine Dinucleotide (NAD) & Nicotine Adenine Dinucleotide Phosphate (NADP) Derivative of Niacin (B 3) Serve as cofactors in oxidation / reduction reactions Act as co-substrates for dehydrogenases ◦ Entity Transferred; Hydride ion (H+ + 2 e-) Electron (Hydrogen atom)

(a reaction of glycolysis) H+ glyceraldehyde 3 P + NAD (substrate) (co substrate) dehydrogenase (enzyme ) • • Di. Phosphoglyceric acid + NADH (product) (NAD act as co-enzyme & H acceptor)

Coenzyme A (Co. A) ◦ Derivative of Pantothenic acid (B 5) ◦ Entity Transferred; Acetyl group and other acyl groups

Pyridoxal Phosphate ◦ PLP is Derivative of Pyridoxine (Vit. B 6) involved in : Transamination reactions required for the synthesis and catabolism of the amino acids. ◦ Decarboxylation reactions. ◦ Entity Transferred; Amino Groups(-NH 2)

Example of co-enzyme in amino acid metabolism NH 2 Glutamate + pyruvate + pyrodoxal P (co-substrate, acceptor Transaminase & donor of amino group) (enzyme) α-Ketoglutaric acid + Alanin

Biotin is a coenzyme for enzymes that transfer carboxyl groups ◦ Entity Transferred; Carbon Dioxide