The ␣-Ketoglutarate Family of Amino Acids Includes Glu, Gln,Pro, Arg, and Lys Amino acids derived from -ketoglutarate include glutamate Glu, glutamine Gln, proline Pro, arginine Arg, an
Trang 1The ␣-Ketoglutarate Family of Amino Acids Includes Glu, Gln,
Pro, Arg, and Lys
Amino acids derived from -ketoglutarate include glutamate (Glu), glutamine
(Gln), proline (Pro), arginine (Arg), and in fungi and protoctists such as Euglena,
lysine (Lys) The routes for Glu and Gln synthesis were described when we
consid-ered pathways of ammonium assimilation
Proline is derived from glutamate via a series of four reactions involving
activation, then reduction, of the -carboxyl group to an aldehyde
(glutamate-5-semialdehyde), which spontaneously cyclizes to yield the internal Schiff base,
1 - pyrroline-5-carboxylate (Figure 25.20) NADPH-dependent reduction of the
pyrro-line double bond gives propyrro-line
Arginine biosynthesis involves enzymatic steps that are also part of the urea
cycle,a metabolic pathway that allows certain animals (including humans) to
ex-crete any excess nitrogen arising from overconsumption of protein Net synthesis
of arginine depends on the formation of ornithine Interestingly, ornithine is
de-rived from glutamate via a reaction pathway reminiscent of the proline
biosyn-thetic pathway (Figure 25.21) Glutamate is first N-acetylated in an acetyl-CoA–
dependent reaction to yield N-acetylglutamate (Figure 25.21) An ATP-dependent
phosphorylation of N-acetylglutamate to give N-acetylglutamate-5- phosphate primes
this substrate for a reduced pyridine nucleotide-dependent reduction to the
semi-aldehyde N -acetyl5-semialdehyde then is aminated by a
glutamate-dependent aminotransferase, giving N-acetylornithine, which is deacylated to
orni-thine In mammals, ornithine is made from glutamate via a pathway that does not
involve an N -acetyl block.
Ornithine has three metabolic roles: (1) to serve as a precursor to arginine, (2) to
function as an intermediate in the urea cycle, and (3) to act as an intermediate in
Arg degradation In any case, the -NH3of ornithine is carbamoylated in a
reac-tion catalyzed by ornithine transcarbamoylase The carbamoyl group is derived
from carbamoyl-P synthesized by carbamoyl-phosphate synthetase I (CPS-I) CPS-I
is the mitochondrial CPS isozyme; it uses two ATPs in catalyzing the formation of
carbamoyl-P from NH3 and HCO3 , one to activate the bicarbonate ion and the
other to phosphorylate the carbamate arising from carboxyphosphate through its
1
NH3+ –O
C O
O
O
P O–
–O
CH2 CH2 C
H C O–
O
NH3+ C
O
CH2 CH2 C
H C O–
O
NAD(P)+
NAD(P)H
2
NH3+ C
O
CH2 CH2 C
H C O–
O
H
3
H2 C
H2 C C
H C
H
O–
O
NAD(P)H
H +
H +
H2O
Pi
+
+
4
NAD(P)+
H
H2
C
H2
C
C
H C
O–
O H
H
Glutamate-5-semialdehyde Proline
Δ1 -Pyrroline-5-carboxylate
FIGURE 25.20 The pathway of proline biosynthesis from glutamate.The enzymes are (1)-glutamyl kinase,
(2) glutamate-5-semialdehyde dehydrogenase, and (4)1-pyrroline-5-carboxylate reductase; reaction (3) occurs
nonenzymatically.
Trang 2reaction with the ammonium ion (Figure 25.22) CPS-I represents the committed
step in the urea cycle, and CPS-I is allosterically activated by N-acetylglutamate Be-cause N-acetylglutamate is both a precursor to ornithine synthesis and essential to
the operation of the urea cycle, it serves to coordinate these related pathways
The product of the ornithine transcarbamoylase reaction is citrulline (Figure
25.23) Ornithine and citrulline are two -amino acids of metabolic importance that nevertheless are not among the 20 -amino acids commonly found in
pro-teins Like CPS-I, ornithine transcarbamoylase is a mitochondrial enzyme The re-actions of ornithine synthesis and the rest of the urea cycle enzymes occur in the cytosol
The pertinent feature of the citrulline side chain is the ureido group In a com-plex reaction catalyzed by argininosuccinate synthetase, this ureido group is first
ac-tivated by ATP to yield a citrullyl-AMP derivative, followed by displacement of AMP
by aspartate to give argininosuccinate (Figure 25.23) The formation of arginine is
then accomplished by argininosuccinase, which catalyzes the nonhydrolytic
elimi-nation of fumarate from argininosuccinate This reaction completes the biosynthe-sis of Arg
1
NH3+ –O
C O
O
–O
P O O–
CH2 CH2 C
H C O–
O
NH C
O
CH2 CH2 C
H C O– O
2
H
5
C O–
O
H3C C
CH3
NH C
O
CH2 CH2 C
H C O
CH3
NAD(P)+
3
NH C
O
CH2 CH2 C
H C
CH3
4
NH
H2O
CH2
H C O
CH3
CH3
CH2 CH2 C
H C
O +H3N
NH3+ +H3N
O
CH2
CH2
ATP
Glutamate
N-Acetylglutamate
N-Acetylglutamate-5-semialdehyde
SCoA
N-Acetylglutamate-5-P
Glutamate
-Ketoglutarate
CoASH
ADP
FIGURE 25.21 The bacterial pathway of ornithine biosynthesis from glutamate The enzymes are
(1) N-acetylglutamate synthase, (2) N-acetylglutamate kinase, (3) N-acetylglutamate-5-semialdehyde
dehydrogenase, (4) N-acetylornithine -aminotransferase, and (5) N-acetylornithine deacetylase.
Trang 3The Urea Cycle Acts to Excrete Excess N Through Arg Breakdown
The carbon skeleton of arginine is derived principally from -ketoglutarate, but the
N and C atoms composing the guanidino group (Figure 25.23) of the Arg side chain
come from NH4 , HCO3 (as carbamoyl-P), and the -NH2groups of glutamate and
aspartate The circle of the urea cycle is closed when ornithine is regenerated from
Arg by the arginase-catalyzed hydrolysis of arginine Urea is the other product of
this reaction and lends its name to the cycle Note that the N atoms in urea arose
from NH4 and the Asp amino group In terrestrial vertebrates, urea synthesis is
re-quired to excrete excess nitrogen generated by increased amino acid catabolism—
for example, following dietary consumption of more than adequate amounts of
pro-tein Urea formation is basically confined to the liver
A healthy adult human male eating a typical American diet will consume about
100 g of protein per day Because such an individual will remain in nitrogen balance
(neither increasing or decreasing his net protein levels), his body must dispose of
about 1 mole of excess N derived from the amino acids in this dietary protein
Glu-tamate is key to this process because of the position of gluGlu-tamate dehydrogenase at
the interface of amino acid and carbohydrate metabolism and the importance of
glu-tamate to the urea cycle
Increases in amino acid catabolism lead to elevated glutamate levels and a rise in
N-acetylglutamate, the allosteric activator of CPS-I Stimulation of CPS-I raises
over-all urea cycle activity because activities of the remaining enzymes of the cycle simply
respond to increased substrate availability Removal of potentially toxic NH4 by
CPS-I is another important aspect of this regulation The urea cycle is linked to the
citric acid cycle through fumarate, a by-product of the action of argininosuccinase
(Figure 25.23, reaction 3)
Lysinebiosynthesis in some fungi and in the protoctist Euglena also stems from
-ketoglutarate, making lysine a member of the -ketoglutarate family of amino acids
+
δ +
1
C
O
O
O–
P
O
O O–
P
O
O O–
P
O
CH2
NH2
O
HO C
O
O–
O–
P O
2
C
O
NH2 –O
–
+
3
O O
O–
P
C NH2
Overall: 2 +HCO3– + NH3
O C
O–
P
O
+ 2 ADP + Pi
Pi
N
N N
ATP
ATP
Bicarbonate ion
NH3
Carbonyl-P
intermediate
Carbamate
Carbamoyl-P
ADP ADP
FIGURE 25.22 The mechanism of action of CPS-I.
Trang 4R
1
P P
H2N C
O
NH2
NH2+
O
C
–O
NH
CH2
C NH3+ H
C
NH2
CH2
CH2
O
–O
C C C C
O
O–
NH2+
O
C
–O
N
CH2
C NH3+ H
C
N
CH2
CH2
H H
C C H
O –O
CH2 C
O
O–
NH2+
O
C
–O
N
CH2
C NH3+ H
C
CH2
CH2
H
O P
O O
–O
NH2
O
C N
CH2
C NH3+ H
C
CH2
CH2
H O
P
O O
–O
O–
C
O
H2N
2a
2b
3 4
NH3+
O
CH2
CH2
CH2
C NH3+ H
C
H H
–O
–O
A
ATP
H2O
Arginine
Fumarate
Argininosuccinate
Citrullyl-AMP
Citrulline
Carbamoyl-P
Citrulline transporter
Citrulline
Aspartate
Guanidino group Urea
Ornithine transporter
Ureido group MITOCHONDRION
Ornithine
Cytosol
AMP
ACTIVE FIGURE 25.23 The urea cycle series of reactions:The enzymes are (1) ornithine
trans-carbamoylase (OTCase), (2a and 2b) argininosuccinate synthetase, (3) argininosuccinase, and (4) arginase Test
yourself on the concepts in this figure at www.cengage.com/login.
Trang 5in these organisms (As we shall see, the other organisms capable of lysine synthesis—
namely, bacteria, other fungi, algae, and green plants—use aspartate as a precursor.)
To make lysine from -ketoglutarate requires a lengthening of the carbon skeleton by
one CH2unit to yield -ketoadipate (Figure 25.24) This addition is accomplished by a
series of reactions reminiscent of the initial stages of the citric acid cycle First, a
two-carbon acetyl-CoA unit is added to the -carbon of -ketoglutarate to form
homo-citrate Then, in a reaction sequence like that catalyzed by aconitase, homoisocitrate
is formed from homocitrate Oxidative decarboxylation (as in isocitrate
dehydroge-nase) removes one carbon (the original -carboxyl group of -ketoglutarate), leaving
-ketoadipate A glutamate-dependent aminotransferase enzyme then aminates
-ketoadipate to give -aminoadipate Next, the -COOgroup is activated in an
ATP-dependent adenylylation reaction, priming this -COOgroup for reduction to an
aldehyde by NADPH -Aminoadipic-6-semialdehyde is then reductively aminated by
ad-dition of glutamate to its aldehydic carbon in an NADPH-dependent reaction leading
to the formation of saccharopine Oxidative cleavage of saccharopine by way of an
NAD-dependent dehydrogenase activity yields -ketoglutarate and lysine This
path-way is known as the ␣-aminoadipic acid pathway of lysine biosynthesis Interestingly,
ly-sine degradation in animals leads to formation of -aminoadipate by a reverse series of
reactions identical to those occurring along the last steps of this biosynthetic pathway
The Aspartate Family of Amino Acids Includes Asp, Asn, Lys,
Met, Thr, and Ile
The members of the aspartate family of amino acids include aspartate (Asp),
as-paragine (Asn), lysine (via the diaminopimelic acid pathway), methionine (Met),
threonine (Thr), and isoleucine (Ile)
Aspartateis formed from the citric acid cycle intermediate oxaloacetate by
trans-fer of an amino group from glutamate via a PLP-dependent aminotranstrans-ferase
reac-tion (Figure 25.25) Like glutamate synthesis from -ketoglutarate, aspartate
syn-thesis is a drain on the citric acid cycle As we already saw, the Asp amino group
serves as the N donor in the conversion of citrulline to arginine In Chapter 26, we
shall see that this ONH2is also the source of one of the N atoms of the purine ring
system during nucleotide biosynthesis, as well as the C-6-amino-group of the major
purine adenine In addition, the entire aspartate molecule is used in the
biosyn-thesis of pyrimidine nucleotides
Asparagineis formed by amidation of the -carboxyl group of aspartate In
bac-teria, in analogy with glutamine synthesis, the nitrogen added in this amidation
comes directly from NH4 In other organisms, asparagine synthetase catalyzes the
ATP-dependent transfer of the amido-N of glutamine to aspartate to yield
gluta-mate, AMP, PP, and asparagine (Figure 25.26)
A DEEPER LOOK
The Urea Cycle as Both an Ammonium and a Bicarbonate Disposal Mechanism
Excretion of excess NH4 in the innocuous form of urea has
tra-ditionally been viewed as the physiological role of the urea cycle
However, the urea cycle also provides a mechanism for the
excre-tion of excess HCO3 arising principally from -carboxyl groups
generated during the catabolism of -amino acids The following
equations illustrate this property:
(1) HCO3 2 NH4 ⎯⎯→ H2NCONH2 2 H2O H
(2) HCO3 H⎯⎯→ H2O CO2
Sum:
2 HCO3 2 NH4 ⎯⎯→ H2NCONH2 CO2 3 H2O
That is, 2 moles of HCO3 are eliminated in the synthesis of each
mole of urea: One is incorporated into the product, urea (reaction
1), and the second is simply protonated and dehydrated to form
CO2(reaction 2), which is easily excreted One interpretation of the
pre-ceding is that these coupled reactions allow a weak acid (NH 4 ) to protonate the conjugate base of a stronger acid (HCO 3 ) At first glance, this
pro-tonation would appear thermodynamically unfavorable, but recall that in the urea cycle, 4 equivalents of ATP are consumed per equiv-alent of urea synthesized: 2 ATPs in the synthesis of carbamoyl-P, and 2 more as 1 ATP is converted to AMP PPiin the synthesis of argininosuccinate from citrulline (Figure 25.23) If this
interpreta-tion is correct, the urea cycle may be considered an ATP-driven proton
pump that transfers H ions from NH 4 to HCO 3 against a thermody-namic barrier In the process, the potentially toxic waste products, ammo-nium and bicarbonate, are rendered innocuous and excreted.
Trang 6H3C
NH3+
P P
C
CH2
CH2
C O
C
C O
C
CH2
CH2 C HO
C O –O
C O–
O
2
C
CH2
CH2
CH C O –O
C O–
O
C
CH2
CH2
C O –O
C O–
O C C
C
CH2
CH2
C O –O
CH2
C
CH2
CH2
C C O –O
CH2 H
4
5 6
NH3+
C
CH2
CH2
C C O –O
CH2 H
O P O O
–O
7
NH3+
H
C
CH2
CH2
C
C
O –O
CH2
H
O
8
NH3+
C
CH2
CH2
C
C
O –O
CH2
H
C O –O
CH2
CH2
C O –O
H
9
NH3+
CH2
CH2
C C O –O
CH2 H
NH3+
CH2
H
Adenosine
CH2
O
ATP
+ + H2O
H2O
H2O
H+
H+
H+
H +
CO 2
-Ketoglutarate
SCoA
+
Homocitrate cis-Homoaconitate Homoisocitrate
+ +
-Ketoadipate
Glu
-KG
-Aminoadipate
Mg 2+
6-Adenylyl--aminoadipate
Mg2+
+
-Aminoadipic-6-semialdehyde
+ +
+ Glutamate
Saccharopine
L -Lysine
NADH
NADPH
NADH
NADP+
NAD+
NADP+
NAD+
CoASH
-KG
FIGURE 25.24 Lysine biosynthesis in certain fungi and Euglena: the
-aminoadipic acid pathway.
Trang 7–O O
C
CH2
C
+
C
CH2 C C
NH3+ H
C
CH2 C C
NH3+ H
CH2
+
C
CH2 C C
CH2
O
Oxaloacetate Glutamate Aspartate -Ketoglutarate
FIGURE 25.25 Aspartate biosynthesis via transamination
of oxaloacetate by glutamate.
HUMAN BIOCHEMISTRY
Asparagine and Leukemia
Leukemia is a cancer of the bone marrow that affects the
production of normal lymphocytes (white blood cells) Acute
lymphoblastic leukemia (ALL) and acute myeloblastic leukemia
(AML) are caused by overproduction of immature lymphocytes.
Both normal and malignant lymphocytes are highly dependent
on the uptake of asparagine from the blood for growth
Admin-istration of E coli asparaginase, an enzyme that converts Asn to
Asp and NH4 (page 806), is one chemotherapeutical approach
to treat childhood ALL and some forms of AML, but patients
of-ten develop resistance to treatment with this “foreign” protein
Inhibition of asparagine synthetase presents an alternative way
to deprive malignant lymphocytes of essential Asn, and
as-paragine synthetase inhibitors might offer a clinical strategy for
treating asparaginase-resistant leukemias The adenylated
sul-foximine shown in the figure is an analog of the aspartyl-AMP
intermediate formed in the asparagine synthetase reaction
(Fig-ure 25.26) In vitro, this compound inhibits asparagine
syn-thetase at nanomolar concentrations The polarity of this
sub-stance limits its ability to cross cell membranes and thus its use
in chemotherapy Hopefully, “second-generation” compounds based on this structure’s affinity for asparagine synthetase will lead to the development of useful drugs to treat these leukemias
OH
NH2
N N
N N O
HO
An adenylated sulfoximine
O
O P
O H
H3N +
O–
CH3
N S –O2C
P P
C
C
C
NH3+
H
CH2
+
O C
C C
NH3+ H
CH2
O C
C C
NH3+ H
CH2
NH2
ATP
AMP
O C
C C
NH3+ H
CH2
NH2
CH2
O C
C C
NH3+ H
CH2
CH2 O–
Step A
[Enz-bound intermediate]
Step B
Asparagine
+
Glutamine
+
Glutamate
AMP
H2O
FIGURE 25.26 Asparagine biosynthesis from Asp, Gln, and ATP by
asparagine synthetase.-Aspartyladenylate is an enzyme-bound
intermediate.
Trang 8Threonine, methionine, and lysine biosynthesis in bacteria proceeds from the
common precursor aspartate, which is converted first to aspartyl- -phosphate and
then to -aspartyl-semialdehyde The first reaction is an ATP-dependent
phosphoryla-tion catalyzed by aspartokinase (Figure 25.27, reacphosphoryla-tion 1) In E coli, there are three
isozymes of aspartokinase, designated aspartokinases I, II, and III Each of these
isozymes is uniquely controlled by one of the three end-product amino acids Form
I is inhibited by threonine and form III, by lysine Form II is not feedback-inhibited, but its synthesis is repressed by methionine
-Aspartyl-semialdehyde is formed via NADPH-dependent reduction of
aspartyl--phosphate in a reaction catalyzed by -aspartyl-semialdehyde dehydrogenase
(Figure 25.27, reaction 2) From here, the pathway of lysine synthesis diverges The methyl carbon of pyruvate is condensed with -aspartyl-semialdehyde, and H2O is
eliminated to yield the cyclic compound 2,3-dihydropicolinate (Figure 25.27, reaction
10) Thus, lysine synthesized by this pathway must be considered a member of both the aspartate and the pyruvate families of amino acids Lysine is a feedback
in-hibitor of this branch-point enzyme Dihydropicolinate is then reduced in an
NADPH-dependent reaction to 1 - piperidine-2,6-dicarboxylate (Figure 25.27, reaction 11) A
series of reactions, including a hydrolytic opening of the piperidine ring, a succiny-lation, a glutamate-dependent amination, and the hydrolytic removal of succinate, results in the formation of the symmetric L , L
-reactions 12 through 14) Epimerization of this intermediate to the meso form, followed by decarboxylation, yields the end product lysine (Figure 25.27,
reac-tions 15 and 16) Because this pathway proceeds through the symmetric L , L -diaminopimelate, one-half of the CO2 evolved in the terminal decarboxylase step
is derived from the carboxyl group of pyruvate and one-half from the -carboxyl
of Asp
The other metabolic branch diverging from -aspartyl-semialdehyde leads to threonine and methionine via homoserine, an analog of serine that is formed by the
NADPH-dependent reduction of -aspartyl-semialdehyde (Figure 25.27, reaction
3) catalyzed by homoserine dehydrogenase From homoserine, the biosynthetic pathways leading to methionine and threonine separate To form methionine, the OOH group of homoserine is first succinylated by homoserine acyltransferase
(Figure 25.27, reaction 6) Methionine is a feedback inhibitor of this enzyme The
succinyl group of O-succinylhomoserine is then displaced by cysteine to yield cys-tathionine (Figure 25.27, reaction 7) The sulfur atom in methionine is contributed
by a cysteine sulfhydryl Cystathionine is then split to give pyruvate, NH4 , and ho-mocysteine, a nonprotein amino acid whose side chain is one OCH2O group longer than that of Cys (Figure 25.27, reaction 8) Methylation of the homocysteine OSH
via methyl transfer from the methyl donor, N5-methyl-THF (see Chapter 26) gives methionine (Figure 25.27, reaction 9)
In passing, it is important to note the role of methionine itself in methylation
re-actions The enzyme S-adenosylmethionine synthase catalyzes the reaction of
methio-nine with ATP to form S-adenosylmethiomethio-nine, or SAM (Figure 25.28) SAM is a substrate
of methyltransferases in a variety of methyl-donor reactions, such as the formation
of phosphatidylcholine from phosphatidylethanolamine (see Figure 8.6) Following decarboxylation, SAM is a source of propylamine for the synthesis of polyamines (Figure 25.28)
The remaining amino acids of the aspartate family are threonine and isoleucine
Threonine,like methionine, is synthesized from homoserine Indeed, homoserine
is the primary alcohol analog of the secondary alcohol Thr To move this OOH from C-4 to C-3 requires activation of the hydroxyl through ATP-dependent
phos-phorylation by homoserine kinase (see Figure 25.27, reaction 4) As the first
reac-tion unique to Thr biosynthesis, homoserine kinase is feedback inhibited by
threo-nine The last step is catalyzed by threonine synthase, a PLP-dependent enzyme (see
Figure 25.27, reaction 5)
Isoleucine is included in the aspartate family of amino acids because four of its six carbons derive from Asp (via threonine) and only two come from pyruvate
Trang 9+ +
1
HC HC
HC
HC HC
HC
HC HC
C
C O
NH3+
CH2
2
C
C
NH3+
CH2
3
C
NH3+
CH2
CH2
O H
4
–O
O
H2O
H2O
H2O
H2O
CO2
Pi
Pi
Pi
H +
H +
H +
H +
C CH2 CH2
5
–O
O
C HC
H C
H C O H
NH3
CH3
6
Succinyl-10
Pyruvate
C
NH3+
CH2
CH2
O Succ
7
Succinate Cysteine
C
NH3+
CH2
CH2 S
CH2
NH3+ C H O
8
C
NH3+
CH2
CH2 HS
9
C
NH3+
CH2
CH2 S
CH3
C
–O
NH3+
CH2
C H OH
CH2
O
10
2
O–
C
O C
O
–O
N
11
O–
C
O C
O
–O
N
Succinyl- +
12
O–
C
O C
O
O
Succ
13
O–
C
O C
O
Succ
H
NH2
C
NH3+
CH2
CH2
CH2
CH2
NH3+
16
C
NH3+
CH2
CH2
CH2
C
C NH3+ H
15
C
NH3+
CH2
CH2
CH2
C C
NH3+ H
14
O
C
C –O
+
+
C
C
CH2
NH3+
ATP
ADP
ADP
NADP+
NADPH
NADPH
CoASH
CoA
CoASH CoA
NADPH
P
O
Aspartate
Aspartyl--phosphate
Phosphohomoserine Threonine
O-Succinylhomoserine
Cystathionine
NH3 + Pyruvate
N5 -Methyl- THF
Homocysteine
THF
Methionine
2,3-Dihydropicolinate
Δ1
-Piperidine-2,6-dicarboxylate
N-Succinyl-2-amino-6-keto-L -pimelate
-Ketoglutarate
Glutamate
N-SuccinylL - L
-Lysine
mesoL - L
-L - L
-Succinate
FIGURE 25.27 Biosynthesis of threonine, methionine, and lysine, members of the aspartate family of amino acids.
Trang 10CH3
NH3+
P P
O
S
CH2
CH2
C C
–O H
+
NH2
N
N N N
O
CH2
NH2
N
N N N
O
CH2
NH2
N
N N N
O
CH2
S+
CH3
CH2
CH2
C NH3+ H
C O –O
Mg2+
S +
CH3
CH2
CH2
NH3+
CH2
CH2 CH2 C C
NH3+
S
H3C
S
CH2
CH2
C NH3+ H
H
C O –O
Adenosine+
NH2
N
N N N
O
CH2
O
O–
HS
CH2CH2CH2CH2
CH2CH2CH2CH2 CH2CH2CH2
+ H2O
H2O
CO2
Methionine
S-Adenosylmethionine (SAM)
S-Adenosylmethionine
decarboxylase
“Decarboxylated SAM”
Methylated products Methyl acceptors
Methyl transferases
Putrescine
Spermidine
Propylamine
transferases
as in putrescine
spermidine
5 ⴕ-Methylthioadenosine
S-Adenosyl
homocysteine ATP
L -Homocysteine
FIGURE 25.28 The synthesis of S-adenosylmethionine (SAM).