1. Dental Biochemistry Review CHO and N Metabolism; Molecular Biology

2. Free energy of a reaction The free energy change (  G) of a reaction determines its spontaneity. A reaction is spontaneous if  G is negative (if the free energy of products is less than that of reactants).  G o ' = standard free energy change (at pH 7, 1M reactants & products); R = gas constant; T = temp.

3. “High energy” bonds Phosphoanhydride bonds (formed by splitting out H 2 O between 2 phosphoric acids or between carboxylic & phosphoric acids) have a large negative  G of hydrolysis.

5. BIOENERGETICS SUMMARY Actual (NOT Standard) Free Energy Change determines reaction spontaneity Enzyme reactions may be coupled to promote reaction spontaneity Free energy is released by hydrolysis of “high energy” molecules (e.g. ATP) Reduced coenzymes (e.g. NADH, FADH) are energy-rich compounds

6. Metabolism of Glucose Catabolic Pathways: Glycolysis (Glucose  Pyruvate + ATP) Citric Acid (TCA) (+ oxidative phosphorylation) Pentose Phosphate Shunt Glycogenolysis Anabolic Pathways: Gluconeogenesis Glycogenesis

10. Phosphofructokinase is usually the rate-limiting step of the Glycolysis pathway. Phosphofructokinase is allosterically inhibited by ATP.  At low concentration, the substrate ATP binds only at the active site.  At high concentration, ATP binds also at a low-affinity regulatory site, promoting the tense conformation.

16. Glycogen Synthesis Ingestion of abundant carbohydrates Blood [glucose] increase Secretion of insulin GLUT 4 translocation Activation of Glycogen Synthase Inactivation of Glycogen Phosphorylase

20. Glycogen Degradation Precondition: Low blood glucose Epinephrine (immediate energy need) Glucagon (need for glucose homeostasis) Liver exports glucose Muscle metabolizes Glucose-6-P

26. Actions of Insulin and Glucagon Metabolic PathwayInsulinGlucagon Glucose UptakeIncreased GlycolysisIncreasedDecreased GluconeogenesisDecreaseIncreased GlycogenesisIncreasedDecreased GlycogenolysisDecreasedIncreased

27. Citric Acid (TCA) Cycle and Electron Transport Complete oxidation of glucose to CO2 + H2O Oxidative Phosphorylation (ATP generation)

33. Biosynthetic “Families” of Amino Acids and their Metabolic Precursors PrecursorAmino Acid(s) α-ketoglutarateGlu (E), Gln (Q), Pro (P), Arg (R) OxaloacetateAsp (D), Asn (B), Met (M), Thr (T), Ile (I), Lys (K) 3-phosphoglycerateSer (S), Cys (C), Gly (G) PEP + Erythrose-4-PPhe (F), Tyr (Y), Trp (W) PyruvateAla (A), Val (V), Leu (L) Ribose-5-PHis (H)

38. Urea Cycle Purpose: Disposal of Nitrogen (ammonia) Urea: the main nitrogenous end product in mammals A source of amino acid (Arginine)

42. Amino Acid Derivatives Amino AcidDerivativeFunction HistamineHistidineVasodilation TyrosineThyroxineIodine carrier Nor/EpinephrineHormone(s) DOPANeurotransmitter DopamineNeurotransmitter TryptophanSerotoninNeurotransmitter MelatoninPigment

46. Synthesis of Heme and Hemoglobin

49. Purine Nucleotide Biosynthesis: PRPP to Inosine monophosphate glycine formyl-THF gln ATP Ring closure CO 2 ATP asp ATP fumarate Ring closure formyl-THF H2OH2O Inosine monophosphate (IMP)

53. Carbamoyl phosphate synthetase II Aspartate transcarbamoylase Dihydroorotase Dihydrorotate dehydrogenase Orotate Phosphoribosyltransferase OMP decarboxylase PRPP orotate UMP Synthase dihydroorotate UMP HCO 3 + Gln + 2ATP De Novo Pyrimidine Synthesis

54. Nomenclature of bases, nucleosides, and nucleotides Pyrimidine BaseRibonucleosideRibonucleotide UracilUridineUridylate (UMP, UDP, UTP) CytosineCytidineCytidylate (CMP, CDP, CTP) ThymineThymidineThymidylate (TMP, TDP, TTP) Purine BaseRibonucleosideRibonucleotide AdenineAdenosineAdenylate (AMP, ADP, ATP) GuanineGuanosineGuanylate (GMP, GDP, GTP)

60. Nucleic Acid Structure and Function DNA RNA Enzyme activities Replication & Transcription

66. DNA Polymerase Successive addition of nucleotides to the end of a growing chain is catalyzed by DNA polymerases. E. coli has 5 DNA polymerases, only three of which are considered here: DNA Pol I: repairs DNA and participates in synthesis of lagging strand during replication DNA Pol II: DNA repair. DNA Pol III: major replication enzyme: responsible for chain elongation during replication; largest of polymerases; key component of replisome. contains 10 different subunits; genes have been isolated. Holoenzyme is an asymmetric dimer consisting of two copies of each polypeptide consisting of a core complex, sliding clamp, and single γ (gamma) complex.

79. Catabolite Repression [Glucose] [cAMP] [Glucose] [cAMP] cAMP-CAP lac operon complex CAP activation of lac operon Lac operon expression stimulated No CAP/lac operon complex No lac operon activation, i.e. catabolite repression low high low high

95. Termination step of protein synthesis