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BIOCHEmISTRY  ``BIOCHEMISTRY—METABOlISM             BIOCHEmISTRY  ``BIOCHEMISTRY—METABOlISM           SECTION II         79




                  Pentose phosphate      Also called HMP shunt. Provides a source of NADPH from abundantly available glucose-6-P
                  pathway                 (NADPH is required for reductive reactions, eg, glutathione reduction inside RBCs, fatty acid
                                          and cholesterol biosynthesis). Additionally, this pathway yields ribose for nucleotide synthesis. Two
                                          distinct phases (oxidative and nonoxidative), both of which occur in the cytoplasm. No ATP is
                                          used or produced.
                                         Sites: lactating mammary glands, liver, adrenal cortex (sites of fatty acid or steroid synthesis), RBCs.

                   REACTIONS
                   Oxidative                               NADP +  NADPH               NADP +  NADPH  CO
                    (irreversible)                                                                    2
                                                 Glucose-6-P
                                                        i                 6-Phosphogluconate            Ribulose-5-P i
                                                        Glucose-6-P dehydrogenase
                   Nonoxidative                                                                              Phosphopentose
                    (reversible)                                                                             isomerase
                                                Fructose-6-P i                                          Ribose-5-P i
                                                                                         Transketolase, B₁

                                                  Fructose                                               Nucleotide
                                               1,6-bisphosphate                                          synthesis


                                             DHAP       Glyceraldehyde-3-P
                                                                   i


                  Glucose-6-phosphate    NADPH is necessary to keep glutathione   X-linked recessive disorder; most common
                  dehydrogenase           reduced, which in turn detoxifies free radicals   human enzyme deficiency; more prevalent
                  deficiency              and peroxides.  NADPH in RBCs leads to   among African Americans.  malarial
                                          hemolytic anemia due to poor RBC defense   resistance.
                                          against oxidizing agents (eg, fava beans,   Heinz bodies—denatured globin chains
                                          sulfonamides, nitrofurantoin, primaquine/  precipitate within RBCs due to oxidative stress.
                                          chloroquine, antituberculosis drugs). Infection   Bite cells—result from the phagocytic removal
                                          (most common cause) can also precipitate   of Heinz bodies by splenic macrophages.
                                          hemolysis; inflammatory response produces   Think, “Bite into some Heinz ketchup.”
                                          free radicals that diffuse into RBCs, causing
                                          oxidative damage.

                                                    Glucose-6-P            NADP +               2 GSH              H O
                                                                                                                    2 2
                                                                                               (reduced)

                                                               Glucose-6-P          Glutathione         Glutathione
                                                              dehydrogenase          reductase          peroxidase


                                                                                                GSSG
                                           6-phosphogluconolactone         NADPH                                    2H O
                                                                                                                      2
                                                                                               (oxidized)























          FAS1_2019_01-Biochem.indd   79                                                                                11/7/19   3:16 PM
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