Carnosine metabolism of glial cells (Homo sapiens)
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Description
This pathway shows the synthesis and degradation of Carnosine as well as the distribution within glial cells in the brain.
The synthesis pathway starts at two different locations, with beta-alanine being transported from the liver and l-histidine being transported from the intestines, since it needs to be ingested. As can be seen, various transports bring these two amino acids across the blood brain barrier and into the oligodendrocyte where the actual synthesis of carnosine happens by CARNS1. The degradation of carnosine also occurs within the oligodendrocyte by CN1 and CN2. The oligdendrocytes are the only glial cells in the brain which produce carnosine, but all of them use it, so distribution to other glial cells is necessary. The transport to microglia is done by SLC14A2 and 4, while transport to astrocytes only requires SLC14A2.
Carnosine also has an impact on the glutamate transporter of the astrocyte, which is SLC1A2, also known as GLT-1. Carnosine stimulates the transporter, which brings more glutamate and sodium into the cell. The sodium concentration within the cell will be increased, leading to a higher activity of the ATPase. This generates more ADP, which can be used within glycolysis. This then builds a connected to the lactate shuttle which occurs between the astrocyte and neurons, in which the astrocyte produces lactate from pyruvate to give the neurons additional energy support.
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