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76          SECTION II    BIOCHEmISTRY  ``BIOCHEMISTRY—METABOlISM                                                                                                   BIOCHEmISTRY  ``BIOCHEMISTRY—METABOlISM





               Glycolysis regulation,   Net glycolysis (cytoplasm):
                                                                 +
                                                                                                   +
               key enzymes           Glucose + 2 P i  + 2 ADP + 2 NAD  Ž 2 pyruvate + 2 ATP + 2 NADH + 2 H  + 2 H 2 O.
                                     Equation not balanced chemically, and exact balanced equation depends on ionization state of
                                       reactants and products.

                REqUIRE ATP           Glucose                       Glucose-6-P  Glucose-6-P ⊝ hexokinase.
                                                Hexokinase/glucokinase
                                                                               Fructose-6-P ⊝ glucokinase.
                                      Fructose-6-P                Fructose-1,6-BP  AMP ⊕, fructose-2,6-bisphosphate ⊕.
                                                 Phosphofructokinase-1
                                                  (rate-limiting step)         ATP ⊝, citrate ⊝.
                PRODUCE ATP           1,3-BPG                            3-PG
                                                  Phosphoglycerate kinase
                                      Phosphoenolpyruvate             Pyruvate  Fructose-1,6-bisphosphate ⊕.
                                                        Pyruvate kinase
                                                                               ATP ⊝, alanine ⊝.


               Regulation by         Fructose bisphosphatase-2 (FBPase-2) and phosphofructokinase-2 (PFK-2) are the same
               fructose-2,6-           bifunctional enzyme whose function is reversed by phosphorylation by protein kinase A.
               bisphosphate                                                  FBPase-1
                                              Gluconeogenesis    Fructose-6-P         Fructose-1,6-BP  Glycolysis
                                                                              PFK-1
                                                            FBPase-2   PFK-2
                                                            (active in  (active in
                                                           fasting state)  fed state)

                                                                 Fructose-2,6-BP
                                     Fasting state:  glucagon Ž  cAMP Ž  protein  FaBian the Peasant (FBP) has to work hard
                                       kinase A Ž  FBPase-2,  PFK-2, less     when starving.
                                       glycolysis, more gluconeogenesis.

                                     Fed state:  insulin Ž  cAMP Ž  protein   Prince FredericK (PFK) works only when fed.
                                       kinase A Ž  FBPase-2,  PFK-2, more
                                       glycolysis, less gluconeogenesis.



               Pyruvate              Mitochondrial enzyme complex linking      The complex is similar to the α-ketoglutarate
               dehydrogenase           glycolysis and TCA cycle. Differentially   dehydrogenase complex (same cofactors,
               complex                 regulated in fed (active)/fasting (inactive) states.  similar substrate and action), which converts
                                                           +
                                     Reaction: pyruvate + NAD  + CoA Ž acetyl-  α-ketoglutarate Ž succinyl-CoA (TCA cycle).
                                      CoA + CO 2  + NADH.
                                     Contains 3 enzymes requiring 5 cofactors:
                                        1.  Thiamine pyrophosphate (B 1 )
                                        2.  Lipoic acid
                                        3.  CoA (B 5 , pantothenic acid)       The Lovely Coenzymes For Nerds.
                                        4.  FAD (B 2 , riboflavin)             Arsenic inhibits lipoic acid. Arsenic poisoning
                                               +
                                        5.  NAD  (B 3 , niacin)                 clinical findings: imagine a vampire (pigmentary
                                                      +
                                     Activated by:  NAD /NADH ratio,  ADP     skin changes, skin cancer), vomiting and having
                                          2+
                                        Ca .                                   diarrhea, running away from a cutie (QT
                                                                                prolongation) with garlic breath.













          FAS1_2019_01-Biochem.indd   76                                                                                11/7/19   3:16 PM
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