20 6 Enzyme Cofactors and Vitamins The ribbon

20. 6 Enzyme Cofactors and Vitamins The ribbon representation of carboxypeptidase shows a Zn 2+ cofactor (orange sphere) in the center of the active site, held in place by amino acid residues in the active site. Learning Goal Describe the types of cofactors found in enzymes. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Enzyme Cofactors • A simple enzyme is an active enzyme that consists only of protein. • Many enzymes are active only when they combine with cofactors such as metal ions or small molecules. • A coenzyme is a cofactor that is a small organic molecule such as a vitamin. Core Chemistry Skill Describing the Role of Cofactors General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Metal Ions as Cofactors Many active enzymes require a metal ion. For example, carboxypeptidase requires a Zn 2+ cofactor for the hydrolysis of the peptide bond of a C-terminal aromatic amino acid. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Vitamins and Coenzymes Vitamins • are organic molecules that are essential for normal health and growth. • are required in trace amounts. • need to be obtained from the diet. • are grouped into water-soluble vitamins and fat-soluble vitamins. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Water-Soluble Vitamins Water-soluble vitamins must come from our food each day; they • are soluble in aqueous solutions and cannot be stored in the body. • are cofactors for many enzymes. • are excreted in urine each day. • are easily destroyed by heat, oxygen, and ultraviolet light, so care must be taken in food preparation. Many of the water-soluble vitamins are precursors of cofactors required by many enzymes to carry out certain aspects of catalytic action. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Function of Coenzymes A coenzyme prepares the active site for catalytic activity. General, Organic,

Thiamine, B 1 Thiamine, associated with coenzyme thiamine pyrophosphate (TPP), • is found in the liver, yeast, whole grain bread, cereals, and milk. • has an RDA of 1. 2 mg. • is necessary to avoid beri, whose symptoms are fatigue, poor appetite, and weight loss. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Riboflavin, B 2 Riboflavin, associated with coenzymes flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), • is found in the liver, beef, chicken, eggs, green leafy vegetables, dairy foods, peanuts, and whole grains. • has an RDA of 1. 2– 1. 8 mg. • is necessary to avoid dermatitis; dry skin; red, sore tongue; and cataracts. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Niacin, B 3 Niacin, associated with coenzymes nicotinamide adenine dinucleotide (NAD 2+) and nicotinamide adenine dinucleotide phosphate (NADP 2+), • is found in brewer’s yeast, chicken, beef, fish, liver, brown rice, and whole grains. • has an RDA of 14– 18 mg. • is necessary to avoid pellagra: dermatitis, muscle fatigue, loss of appetite, diarrhea, and mouth sores. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Pantothenic Acid, B 5 Pantothenic acid, associated with coenzyme A, • is found in salmon, beef, liver, eggs, brewer’s yeast, whole grains, and fresh vegetables. • has an RDA of 5 mg. • is necessary to avoid fatigue, retarded growth, muscle cramps, and anemia. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Pyridoxine, B 6 Pyridoxine, associated with pyridoxal phosphate (PLP), • is found in meat, liver, fish, nuts, whole grains, and spinach. • has an RDA of 1. 3– 2. 0 mg. • is necessary to avoid dermatitis, fatigue, anemia, and retarded growth. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Folic Acid, B 9 Folic acid, associated with tetrahydrofolate (THF), • is found in green leafy vegetables, beans, meat, seafood, yeast, asparagus, and whole grains enriched with folic acid. • has an RDA of 400 mcg. • is necessary to avoid abnormal red blood cells, anemia, intestinal tract disturbances, loss of hair, growth impairment, and depression. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Cobalamin, B 12 Cobalamin, associated with methylcobalamin, • is found in liver, beef, kidney, chicken, fish, and milk products. • has an RDA of 2. 0– 2. 6 mcg. • is necessary to avoid pernicious anemia, malformed red blood cells, and nerve damage. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Ascorbic Acid, C Ascorbic acid • is found in blueberries, citrus fruits, strawberries, cantaloupe, tomatoes, peppers, broccoli, cabbage, and spinach. • has an RDA of 75– 90 mg. • is necessary to avoid scurvy: bleeding gums, weakened connective tissues, slow-healing wounds, and anemia. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Biotin, H Biotin, associated with biocytin, • is found in liver, yeast, nuts, and eggs. • has an RDA of 30 mcg. • is necessary to avoid dermatitis, loss of hair, fatigue, anemia, and depression. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Study Check Identify each enzyme as 1) a simple enzyme. 2) an enzyme that requires a cofactor. A. requires Mg 2+ for hydrolysis of phosphate esters B. requires vitamin B 3 to transfer an acetyl group C. is active with four polypeptide subunits General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Solution Identify each enzyme as 1) a simple enzyme. 2) an enzyme that requires a cofactor. 2 A. requires Mg 2+ for hydrolysis of phosphate esters 2 B. requires vitamin B 3 to transfer an acetyl group 1 C. is active with four polypeptide subunits General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Fat-Soluble Vitamins Fat-soluble vitamins • include A, D, E, and K and are not involved as coenzymes in catalytic reactions. • are soluble in lipids but not in aqueous solutions. • are stored in the body and not eliminated in urine. • are important in vision, bone formation, antioxidants, and blood clotting. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Retinol (Vitamin A) Vitamin A, an antioxidant, • is needed for retinol (vision) and synthesis of RNA. • has an RDA of 800 g. • is necessary to avoid night blindness, immune system repression, and slowed growth. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Cholecalciferol (Vitamin D) Vitamin D (D 3) • is synthesized in skin exposed to sunlight. • regulates the absorption of phosphorus and calcium during bone growth. • has an RDA of 5– 10 μg. • is necessary to avoid weakened bones. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Tocopherol (Vitamin E) Vitamin E • is an antioxidant in cells. • is found in whole grains and vegetables. • has an RDA of 15 mg. • is necessary to avoid hemolysis and anemia. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Menaquinon (Vitamin K) Vitamin K • is needed for the synthesis of zymogens for blood clotting. • has an RDA of 90– 120 mcg. • is necessary to avoid prolonged bleeding time and bruising. General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Study Check Identify each of the following as a water-soluble vitamin (WS) or fat-soluble vitamin (FS): A. folic acid B. retinol (vitamin A) C. vitamin C D. vitamin E E. niacin General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Solution Identify each of the following as a water-soluble vitamin (WS) or fat-soluble vitamin (FS): A. folic acid WS B. retinol (vitamin A) FS C. vitamin C WS D. vitamin E FS E. niacin WS General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Study Check Identify the vitamin associated with each of the following: 1) riboflavin (B 2) 2) vitamin A 3) vitamin K 4) vitamin D 5) ascorbic acid A. B. C. D. E. collagen formation part of the coenzymes FAD and FMN absorption of phosphorus and calcium in bone vision blood clotting General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.

Solution Identify the vitamin associated with each of the following: 1) riboflavin (B 2) 2) vitamin A 3) vitamin K 4) vitamin D 5) ascorbic acid 5 1 4 2 3 A. B. C. D. E. collagen formation part of the coenzymes FAD and FMN absorption of phosphorus and calcium in bone vision blood clotting General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C. Timberlake © 2016 Pearson Education, Inc.