Advanced Biochemistry and Chemical Biology CHM4034 Spring 2008 Dr. Lyons office hours W AM -T,R 4:00-5:00 PM Class website

Monosaccharides are modified

Aldonic AcidAldose Uronic Acid Glucose Gluconic AcidGlucuronic Acid Oxidation reduction reactions : The aldehyde moiety in aldoses can be oxidize to yield a carboxylic acid, the resulting compounds are known as aldonic acids.

Monosaccharides are modified

Ribose Ribitol - The reduction of the carbonyl group in aldoses and ketoses yields polyols known as alditols

Glycerol Inositol

Nucleic Acids The Ultimate Building Blocks

Purines Adenosine NUCLEOSIDE Adenosine monophosphate NUCLEOTIDE Adenine BASE Deoxyadenosine DEOXYNUCLEOSIDE Deoxyadenosine monophosphate DEOXYNUCLEOTIDE

Purines Guanine BASE Guanosine NUCLEOSIDE Guanosine monophosphate NUCLEOTIDE Deoxyguanosine DEOXYNUCLEOSIDE Deoxyguanosine monophosphate DEOXYNUCLEOTIDE

Pyrimidines Cytosine BASE Cytidine NUCLEOSIDE Cytidine monophosphate NUCLEOTIDE Deoxycytidine DEOXYNUCLEOSIDE Deoxycytidine monophosphate DEOXYNUCLEOTIDE

Pyrimidines (DNA only) Thymine BASE Thymidine NUCLEOSIDE Thymidine monophosphate NUCLEOTIDE Deoxythymidine DEOXYNUCLEOSIDE Deoxythymidine monophosphate DEOXYNUCLEOTIDE

Pyrimidines (RNA only) Uracil BASE Uridine NUCLEOSIDE Uridine Monophosphate NUCLEOTIDE

Nucleotide monphosphate Nucleotide diphosphate Nucleotide triphosphate AMP/dAMP ADP/dADP ATP/dATP

BaseNucleosideDeoxy Nucleoside NucleotideDeoxy Nucleotide Adenine A Adenosine A Deoxyadenosine dA Adenosine mono, di, triphosphate AMP, ADP, ATP Deoxyadenosine mono, di, triphosphate dAMP, dADP, dATP Thymine T Thymidine T Deoxythymidine dT Thymidine mono, di, triphosphate TMP, TDP, TTP Deoxythymidine mono, di, triphosphate dTMP, dTDP, dTTP Cytosine C Cytidine C Deoxycytidine dC Cytidine mono, di, triphosphate CMP, CDP, CTP Deoxycytidine mono, di, triphosphate dCMP, dCDP, dCTP Guanine G Guanosine G Deoxyguanosine dG Guanosine mono, di, triphosphate GMP, GDP, GTP Deoxyguanosine mono, di, triphosphate dAMP, dADP, dATP Uracil U Uridine U Deoxyuridine dU Uridine mono, di, triphosphate UMP, UDP, UTP Deoxyuridine mono, di, triphosphate dUMP, dUDP, dUTP

Signaling nucleotides

The stability of RNA v. DNA

Functions for nucleotides other than for DNA/RNA Enter ATP GTP, CTP, UTP and TTP also used in this capacity

NADP + has a 2’ phosphate

Ribitol

Cobalamin Vitamin B 12 Becomes Coenzyme B 12

Fatty Acids

Nomenclature Saturated = -anoic acid, -anoate Unsaturated = -enoic acid, -enoate Take the example of fatty acid with 16 carbons 16 carbon hydrocarbon = hexadecane Fatty acid C16:0 hexadecanoic acid (hexadecanoate) palmitic acid (palmitate) 1 double bond = C16:1, hexadecenoic acid 2 double bonds = C16:2, hexadecadienoic acid Three systems of nomenclature symbol, systematic, common

SymbolCommon NameSystematic Name 12:0Lauric acidDodecanoic acid 14:0Myristic acidTetradecanoic acid 16:0Palmitic acidHexadecanoic acid 16:1 ∆9Palmitoleic acid9-Hexadecenoic acid 18:0Stearic acidOctadecanoic acid 18:1 ∆9Oleic acid9-octadecenoic acid 18:2 ∆9∆12Linoleic acid9,12-octadecadienoic acid 18:3 ∆9∆12∆15Linolenic acid9,12,14-octadecatrienoic acid 20:0Arachidic acidEicosanoic acid 20:4 ∆5∆8∆11∆14Arachidonic acid5,8,11,14-eicosatetraenoic acid 20:5 ∆5∆8∆11∆14∆17Eicospentaenoic acid5,8,11,14,17- eicosapentaenoic acid 22:0Behenic acidDocosanoic acid 24:0Lignoceric acidTetracosanoic acid 24:1 ∆15Nervonic acid15-tetracosenoic acid

Storage lipids/Neutral lipids Triglycerides Triacylglycerol Sterylesters

Structural Lipids - Membrane components Glycerolipids Sphingolipids Diphytanyl lipids

Signaling Lipids Ceramides Inositol containing lipids Eicosanoids Steroids

Thiamine pyrophosphate (TPP)

Phosphohexose isomerase

Breaking a C-C bond between  and  carbons

Enolase

Pyruvate kinase

Acetyl CoA Citrate Synthase Oxaloacetate Claisen condensation Ligase

Aconitase: lyase

Breaking a C-C bond between  and  carbons

With a  keto acid To decarboxylate you need an electron withdrawing group Use you can generate an enolate that can be stabilized by metals, Schiff’s base, etc…

Isocitrate dehydrogenase: oxidoreductase IsocitrateOxalosuccinate

Isocitrate dehydrogenase: oxidoreductase  -ketoglutarate Oxalosuccinate + CO 2 Enol intermediate

Breaking a C-C bond between carbonyl carbon and  carbon NEED TO STABILIZE CARBANION

With an  keto acid To decarboxylate you need an electron withdrawing group Use thiamine pyrophosphate to attack the  carbonyl

Almost the Same Reaction as pyruvate dehydrogenase/decarboxylase  -ketoglutarate dehydrogenase

 -ketoglutarate dehydrogenase

Succinyl-CoA

Succinyl-CoA synthetase: transferase Succinyl-CoA Succinyl-phosphateSuccinate Phosphoenzyme

Succinyl-CoA synthetase: transferase Phosphoenzyme

Succinate dehydrogenase: oxidoreductase Succinate Fumarate

Fumarase: lyase FumarateMalate

Malate dehydrogenase oxaloacetate Malate