Biosynthesis and biodegradation In organisms, methylglyoxal is formed as a side-product of several
metabolic pathways. Methylglyoxal mainly arises as side products of
glycolysis involving
glyceraldehyde-3-phosphate and
dihydroxyacetone phosphate. It is also thought to arise via the degradation of
acetone and
threonine. It may form from
3-aminoacetone, which is an intermediate of threonine
catabolism, as well as through
lipid peroxidation. However, the most important source is
glycolysis. Here, methylglyoxal arises from nonenzymatic phosphate elimination from glyceraldehyde phosphate and
dihydroxyacetone phosphate (DHAP), two intermediates of glycolysis. This conversion is the basis of a potential biotechnological route to the commodity chemical
1,2-propanediol. Since methylglyoxal is highly
cytotoxic, several detoxification mechanisms have evolved. One of these is the
glyoxalase system. Methylglyoxal is detoxified by
glutathione. Glutathione reacts with methylglyoxal to give a
hemithioacetal, which converted into
S--lactoyl-glutathione by
glyoxalase I. This
thioester is hydrolyzed to
-lactate by
glyoxalase II.
Biochemical function Methylglyoxal is involved in the formation of
advanced glycation end products (AGEs). In this process, methylglyoxal reacts with free amino groups of
lysine and
arginine and with thiol groups of
cysteine forming AGEs.
Argpyrimidine is one example.
Histones are also heavily susceptible to modification by methylglyoxal and these modifications are elevated in breast cancer.
DNA damages are induced by reactive
carbonyls, principally methylglyoxal and
glyoxal, at a frequency similar to that of
oxidative DNA damages. Such damage, referred to as DNA
glycation, can cause
mutation, breaks in DNA and
cytotoxicity. Methylglyoxal binds directly to the nerve endings and by that increases the chronic extremity soreness in
diabetic neuropathy. ==Occurrence, other==