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One-Carbon MetabolismOne-Carbon Metabolism

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					•     C      H         A       P       T         E       R   •       21   •



                   ONE-CARBON
                   METABOLISM
                                        •
One-Carbon Metabolism
Oxidation States of Carbon



•      •     •     •       •       •         •       •   •       •    •   •



    ONE-CARBON METABOLISM
    Function: To donate methyl groups to phospholipid, biogenic
       amines, thymidine, and amino acid biosynthesis
       To provide one-carbon fragments at the level of formaldehyde
       and formic acid for purine and pyrimidine biosynthesis
    Location: Most everywhere
    Connections: One-carbon fragments in from serine, glycine, for-
       mate, and histidine
       One-carbon fragments out from SAM, formyl-THF, methylene-
       THF, and methyl-THF
    Regulation: At individual enzyme level


(See Fig. 21-1.)


    OXIDATION STATES OF CARBON
    Count the number of carbons and hydrogens connected to the car-
    bon in question. Carbon–carbon double bonds count only once. The
    lower the number, the more oxidized the carbon. Conversions
    between levels require oxidizing or reducing agents. Conversions
    within a given level require no oxidizing or reducing agents.


                                       233
•   234   •                                                                   Basic Concepts in Biochemistry



                                                                     CH3




                                                                     —
                                         Pi     PPi          Ade — S — CH2CH(NH3)CO2
                                                                                                       Acceptor
                                       ATP                      S-Adenosylmethionine


                                        CH3S — CH2CH(NH3)CO2                                           CH3 Acceptor
                                                methionine

                                                                         Ade — S — CH2CH(NH3)CO2
                                    H4 Folate                                    S-Adenosylhomocysteine
      serine
                                                        B12
        serine              formate   Histidine        enzyme
transhydroxymethylase
                                O
                           H
      glycine                   H4 Folate                         HS — CH2CH(NH3)CO2
                                                       CH3               homocysteine
                                       NADPH
                                                      —




                          CH2                      H4 Folate
                        H4 Folate
                                                                          cystathionine
                                                 NADPH

                                                                                          2-ketobutyrate


                                                                            cysteine


Figure 21-1             One-Carbon Metabolism



     Determining the oxidation state of a specific carbon atom is simple.
Just count the number of carbon and hydrogen atoms that the carbon
atom in question is connected to. Carbon–carbon double bonds count
only once. A more reduced carbon has a higher number, and a more oxi-
dized carbon has a lower number. Carbon atoms can be in five different
oxidation states.1 Being in a different oxidation state means that some
source of oxidizing or reducing agent must be used to convert carbon in
one oxidation state to carbon in another oxidation state. In terms of the
table following, this means that to move up in the table (to a more
reduced form of carbon) requires a reducing agent such as NADH. Mov-
ing down the table requires an oxidizing agent such as NAD or oxy-
gen. Moving between successive oxidation states represents a
two-electron oxidation or reduction. Conversion of carbon within a given
redox state does not require an oxidizing or reducing agent.



1
  This doesn’t count carbon atoms with single electrons (free radicals). You’ve got to draw the
line somewhere, and I’ve chosen to eliminate the more radical elements. If you want to put
them in, you can draw your own table.
21   One-Carbon Metabolism                                                           •   235   •


     For example, converting methylene-THF [ N CH2 N , state 2]2
to formyl-THF [ N C(“O) H, state 1] would require an oxidizing
agent. In contrast, conversion of formyl-THF [ N C(“O) H, state 1]2
to methenyl-THF ( N CH“N , state 1) would not require an oxidiz-
ing or a reducing agent. The way to think about the conversion between
methenyl-THF and formyl-THF is that the reaction is simply the addi-
tion of another amino group from the THF to the C“O of the formyl
group followed by the elimination of water. In none of the reactions does
the carbon atom change its oxidation state.2

       —N—CH(“O)                 NH2—R ∆ —N—CH(OH)—NH—R
              —N—CH(OH)—NH—R ∆ —N—CH“N—R                                        H2O

By comparison, the conversion of methenyl-THF ( N CH“N R,
state 1) to methylene-THF ( N CH2 N , state 2) requires a reducing
agent, NADPH.


     REDUCTION                                TYPICAL                  FOLIC ACID
       LEVEL             NAME               STRUCTURES                EQUIVALENT2

          4          Methane              CH4                       None
                                          CH3—C
                                          C—CH2—C
          3          Methanol             CH3OH                     Methyl-THF
                                          CH3C1                     (—N—CH3)
                                          CH2“C—
          2          Formaldehyde         H—C(“O)—H                 Methylene-THF
                                          H—C(OH)2—H                (—N—CH2—N—)
          1          Formic acid          H—C(“O)—OH                Formyl-THF
                                                                    (—N—C(“O)—H)
                                                                    Methenyl-THF
                                                                    (—N—CH“N—)
          0          Carbon dioxide       O“C“O         None
                                          HO—C(“O)—OH
                                          H2N—C(“O)—NH2



2
 The structural features shown in parentheses or brackets represent the structure of the one-
carbon fragment attached to the N5 and N10 of tetrahydrofolate. The bonds to carbon are as
shown, but for simplicity all the bonds to N may not be shown.

				
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Description: One-Carbon Metabolism