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2016-03-07 Metabolism consists of oxidation-reduction reactions Course 2851 Principles of Metabolism Metabolism and endocrinology programme, Karolinska Institutet • • Catabolism = oxidation of carbon + 6 O2 Lecture 3 6 CO2 + 6 H2O Oxidation and reduction Atom H P C S N O Total number of electrons donated ( + ) or received ( – ) from bound atoms Oxidation state = (# bonds shared with N, O) – (# bonds shared with H, P) O Highly reduced “energy rich” Anabolism = reduction of carbon Highly oxidized “energy poor” Functional group —CH3 —CH2— —CH=CH— —CH(NH2) — —CH(OH) — —CH=O —(C=O) — —COOH CO2 State -3 -2 -1 0* 0 +1 +2 +3 +4 More electronegative ? ?—C—? — e– (energy carrier, e.g. NAD) E 2.3 2.3 2.5 2.6 3.0 3.6 — Department of Medicine, Solna Center for Molecular Medicine Karolinska Institutet C The ability of an atom to attract electrons Electrons “prefer” more electronegative atoms – favorable Oxidation state of carbon • Glucose Roland Nilsson, Ph.D Electronegativity ? 1 2016-03-07 Oxidation state of common metabolites Oxidation state of common metabolites Oxidation state of common metabolites Highly reduced “energy rich” Highly reduced “energy rich” Highly reduced “energy rich” Functional group —CH3 —CH2— —CH=CH— —CH(NH2) — —CH(OH) — —CH=O —(C=O) — —COOH CO2 Highly oxidized “energy poor” State -3 -2 -1 0* 0 +1 +2 +3 +4 Choline Methionine Functional group —CH3 —CH2— —CH=CH— —CH(NH2) — —CH(OH) — —CH=O —(C=O) — —COOH CO2 Highly oxidized “energy poor” State -3 -2 -1 0* 0 +1 +2 +3 +4 Palmitate (saturated fat) Functional group —CH3 —CH2— —CH=CH— —CH(NH2) — —CH(OH) — —CH=O —(C=O) — —COOH CO2 State -3 -2 -1 0* 0 +1 +2 +3 +4 Arachidonate (unsaturated fat) Highly oxidized “energy poor” 2 2016-03-07 Oxidation state of common metabolites Oxidation state of common metabolites Oxidation state of common metabolites Highly reduced “energy rich” Highly reduced “energy rich” Highly reduced “energy rich” Functional group —CH3 —CH2— —CH=CH— —CH(NH2) — —CH(OH) — —CH=O —(C=O) — —COOH CO2 Highly oxidized “energy poor” State -3 -2 -1 0* 0 +1 +2 +3 +4 Glutamate Histamine Functional group —CH3 —CH2— —CH=CH— —CH(NH2) — —CH(OH) — —CH=O —(C=O) — —COOH CO2 Highly oxidized “energy poor” State -3 -2 -1 0* 0 +1 +2 +3 +4 Glucose Functional group —CH3 —CH2— —CH=CH— —CH(NH2) — —CH(OH) — —CH=O —(C=O) — —COOH CO2 State -3 -2 -1 0* 0 +1 +2 +3 +4 Glyceraldehyde Highly oxidized “energy poor” 3 2016-03-07 Oxidation state of common metabolites Oxidation state of common metabolites Oxidation state of common metabolites Highly reduced “energy rich” Highly reduced “energy rich” Highly reduced “energy rich” Functional group —CH3 —CH2— —CH=CH— —CH(NH2) — —CH(OH) — —CH=O —(C=O) — —COOH CO2 Highly oxidized “energy poor” State -3 -2 -1 0* 0 +1 +2 +3 +4 Acetoacetate Functional group —CH3 —CH2— —CH=CH— —CH(NH2) — —CH(OH) — —CH=O —(C=O) — —COOH CO2 Highly oxidized “energy poor” State -3 -2 -1 0* 0 +1 +2 +3 +4 Citrate Functional group —CH3 —CH2— —CH=CH— —CH(NH2) — —CH(OH) — —CH=O —(C=O) — —COOH CO2 State -3 -2 -1 0* 0 +1 +2 +3 +4 CO2 Highly oxidized “energy poor” 4 2016-03-07 Can we predict what reactions will happen? Redox perspective of metabolism Electron carriers compartmentalize redox metabolism Reduction Pyruvate to lactate Oxidizing a-ketoglutarate +2 +4 0 +3 Saturated fat Methyl groups (choline) +2 Reduced substrate Sugars one-carbon metabolism Pyruvate Lactate +3 succinate a-ketoglutarate Unfavorable, proceeds to the left Favorable, proceeds to the right Nucleobases glycolysis Fatty acid synthesis Oxidation Energy metabolism Peptide bond R Amino acids puryvate +3 +3 R R Reduction Biosynthesis NADP NADPH Acetyl-CoA Oxidized product TCA cycle Amino acid 2 NAD / FAD NADH / FADH2 Ketone bodies R + Amino acid 1 Reduced product Unsaturated fat Oxidized substrate Dipeptide Carboxylates (citrate) Borderline case! But electroneg. of N = 3.0 < O = 3.6 CO2 Oxidation 5