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Methionine
Breath Test Background |
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Defective Methionine Metabolism in Cirrhosis
Methionine is an essential amino
acid because of its role as a one-carbon methyl donor
and the main source of sulfur groups for other amino
acids. The metabolism of methionine comprises an initial
transfer of its methyl group to methyl acceptors (transmethylation
pathway) followed by a catabolic pathway, the transsulfuration
pathway, which leads to the formation of other sulfur-containing
amino acids. Delayed methionine clearance, decreased
concentration of methionine end products and hypermethioninemia
has been associated with cirrhosis (1,2).
A block of the transsulfuration pathway was suggested
as the reason for these changes in methionine metabolism
during liver disease. Marchesini et al. measured the
plasma clearance of exogenous methionine during steady-state
conditions in cirrhotic patients and in control subjects
(3).
Methionine clearance was reduced and methionine half-life
increased in cirrhotic patients compared to controls.
The study supports reduced metabolism of methionine
via the transsulfuration pathway in cirrhosis. Russmann,
Junker and Lauterburg recently reportedusing a dual
labeled methionine tracer that the transsulfuration
pathway is blocked in cirrhosis but not the transmethylation
pathway (4).
The transsulfuration pathway occurs in the mitochondria
of hepatocytes exclusively. Methionine is oxidized
in the mitochondria on the first carbon to CO2.
Loss of mitochondrial function due to liver disease
will impair the transsulfuration oxidative pathway.
Addressing the need for a non-invasive liver function
test
Metabolic Solutions, Inc. has developed a non-invasive
breath test that determines the degree and progression
of liver impairment in patients with varied causes
of liver disease. The test is based on the metabolism
of 1-13C methionine by hepatic mitochondria
and is called the methionine breath test.
The methionine breath test represents an exciting
new method for determining liver disease severity
because it is a non-invasive, specific, and quantitative
measure of hepatic mitochondrial function. Our studies
demonstrate the effectiveness of the methionine breath
test in measuring hepatic mitochondrial function in
individuals with liver disease.
Principle of the Methionine Breath Test:
Methionine is an essential amino acid that has important
roles in various metabolic processes, including protein
synthesis. The methionine breath test uses 13C-methionine,
which is a non-radioactive isotope and is metabolized
exclusively by hepatic mitochondria. Subsequent to a
dose, 13C-methionine metabolism results in
an increased concentration of 13CO2
in expired breath. The principle behind this technology
is that the quantity of 13CO2 measured
in breath correlates with liver disease severity. The
biochemistry of methionine metabolism is illustrated
in figure 1.
Figure 1:13C-Methionine Metabolism
Literature Cited:
1. Kinsell LW, Harper HA, Barton HC, Michaels GD, Weiss
HA. (1947) Rate of disappearance from plasma of intravenously
administered methionine in patients with liver damage.
Science 106:589-590.
2. Horowitz JH, Rypins EB, Henderson JM, Heymsfield
SB, Moffitt SD, Bain BP, Chawla RK, et al. (1981) Evidence
for impairment of transsulfuration pathway in cirrhosis.
Gastroenterology 81:668-75.
3. Marchesini G, Bugianesi E, Bianchi G, Fabbri A, Marchi
E, Zoli M, and Psi E.(1992) Defective methionine metabolism
in cirrhosis: Relation to severity of liver disease.
Hepatology 16:149-155.
4. Russmann S, Junker E, and Lauterburg BH. (2002) Remethylation
and transsulfuration of methionine in cirrhosis: studies
with L-[H3-methyl-1-13C]methionine.
Hepatology 36:1190-6.
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Nashua, NH 03063
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