Biochemistry 2/e - Garrett & Grisham Chapter 18 Metabolism an Overview to accompany Biochemistry, 2/e by Reginald Garrett and Charles Grisham All rights reserved Requests for permission to make copies of any part of the work should be mailed to: Permissions Department, Harcourt Brace & Company, 6277 Sea Harbor Drive, Orlando, Florida 32887-6777 Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Outline • • • • • 18.1 Basic Set of Metabolic Pathways 18.2 Catabolism and Anabolism 18.3 Experimental Methods 18.4 Nutrition SPECIAL FOCUS: Vitamins Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Metabolism • The sum of the chemical changes that convert nutrients into energy and the chemically complex products of cells • Hundreds of enzyme reactions organized into discrete pathways • Substrates are transformed to products via many specific intermediates • Metabolic maps portray the reactions Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham A Common Set of Pathways • Organisms show a marked similarity in their major metabolic pathways • Evidence that all life descended from a common ancestral form • There is also significant diversity • Autotrophs use CO2; Heterotrophs use organic carbon; Phototrophs use light; Chemotrophs use Glc, inorganics & S Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham The Sun is Energy for Life • Phototrophs use light to drive synthesis of organic molecules • Heterotrophs use these as building blocks • CO2, O2, and H2O are recycled • See Figure 18.3 Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Metabolism • Metabolism consists of catabolism and anabolism • Catabolism: degradative pathways – Usually energy-yielding! • Anabolism: biosynthetic pathways – energy-requiring! Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Organization in Pathways • • • • • Pathways consist of sequential steps The enzymes may be separate Or may form a multienzyme complex Or may be a membrane-bound system New research indicates that multienzyme complexes are more common than once thought Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Biotin • • • • "Chemistry on a tether" Biotin functions as a mobile carboxyl group carrier Bound covalently to a lysine The biotin-lysine conjugate is called biocytin The biotin ring system is thus tethered to the protein by a long, flexible chain Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Biotin Carboxylations Most use bicarbonate and ATP • Whenever you see a carboxylation that requires ATP and CO2 or HCO3-, think biotin! • Activation by ATP involves formation of carbonyl phosphate (aka carboxyl phosphate) • Carboxyl group is transferred to biotin to form Ncarboxy-biotin • The "tether" allows the carboxyl group to be shuttled from the carboxylase subunit to the transcarboxylase subunit of ACC-carboxylase Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Lipoic Acid Another example of "chemistry on a tether"! • Lipoic acid, like biotin, is a ring on a chain and is linked to a lysine on its protein • Lipoic acid is an acyl group carrier • Found in pyruvate dehydrogenase and -ketoglutarate dehydrogenase • Lipoic acid functions to couple acyl-group transfer and electron transfer during oxidation and decarboxylation of -keto acids Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Folic Acid Folates are donors of 1-C units for all oxidation levels of carbon except that of CO2 • Active form is tetrahydrofolate (THF) • THF is formed by two successive reductions of folate by dihydrofolate reductase • Know how to calculate oxidation states of C! • See Table 18.6 Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Vitamin A Retinol, retinyl esters and retinal are forms of Vitamin A • Retinol-binding proteins (RBPs) help to mobilize and transport vitamin A and its derivatives • Retinol is converted to retinal in the retina of the eye and is linked to opsin to form rhodopsin, a light-sensitive pigment protein in the rods and cones • Vitamin A also affects growth and differentiation Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Vitamin D Ergocalciferol and cholecalciferol • Cholecalciferol is made in the skin by the action of UV light on 7-dehydrocholesterol • Major circulating form is 25-hydroxyvitamin D • 1,25-dihydroxycholecalciferol (1,25dihydroxyvitamin D3) is the most active form • It functions to regulate calcium homeostasis • and plays a role in phosphorus homeostasis Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Vitamins E and K • • • • • Less understood vitamins Vitamin E (-tocopherol) is a potent antioxidant Molecular details are almost entirely unknown May prevent membrane oxidations Vitamin K is essential for blood clotting Carboxylation of 10 glutamyl residues on prothrombin (to form -carboxy-Glu residues) is catalyzed by a vitamin K-dependent enzyme, liver microsomal glutamyl carboxylase Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company Biochemistry 2/e - Garrett & Grisham Copyright © 1999 by Harcourt Brace & Company