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ONE-CARBON
METABOLISM
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One-Carbon Metabolism
Oxidation States of Carbon
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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, formate, and histidine
One-carbon fragments out from SAM, formyl-THF, methyleneTHF, 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 carbon 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
BG McGraw-Hill: Gilbert, Basic Concepts in Biochemistry, JN 5036
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Basic Concepts in Biochemistry
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CH3
Pi PPi
Ade — S — CH2CH(NH3)CO
2
S-Adenosylmethionine
ATP
Acceptor
CH3S — CH2CH(NH3)CO
2
CH3 Acceptor
methionine
serine
glycine
S-Adenosylhomocysteine
formate
Histidine
O
H
H4 Folate
NADPH
CH2
H4 Folate
B12
enzyme
CH3
—
serine
transhydroxymethylase
Ade — S — CH2CH(NH3)CO
2
H4 Folate
HS — CH2CH(NH3)CO
2
homocysteine
H4 Folate
NADPH
cystathionine
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 oxidized 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. Moving down the table requires an oxidizing agent such as NAD or oxygen. 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.
BG McGraw-Hill: Gilbert, Basic Concepts in Biochemistry, JN 5036
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One-Carbon Metabolism
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For example, converting methylene-THF [NCH2N, state 2]2
to formyl-THF [NC(“O)H, state 1] would require an oxidizing
agent. In contrast, conversion of formyl-THF [NC(“O)H, state 1]2
to methenyl-THF (NCH“N, state 1) would not require an oxidizing or a reducing agent. The way to think about the conversion between
methenyl-THF and formyl-THF is that the reaction is simply the addition 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 (NCH“NR,
state 1) to methylene-THF (NCH2N, state 2) requires a reducing
agent, NADPH.
REDUCTION
LEVEL
NAME
TYPICAL
STRUCTURES
FOLIC ACID
EQUIVALENT2
4
Methane
CH4
CH3—C
C—CH2—C
None
3
Methanol
CH3OH
CH3C1
CH2“C—
Methyl-THF
(—N—CH3)
2
Formaldehyde
H—C(“O)—H
H—C(OH)2—H
Methylene-THF
(—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 onecarbon 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.
BG McGraw-Hill: Gilbert, Basic Concepts in Biochemistry, JN 5036