Biomedical Engineering Reference
In-Depth Information
these transporters restricts transfer of monocarboxylates from the basolateral surface
out into the gut lumen.
7.2.2. Tissue Distribution and Subcellular Localization of SMCTs
Adding to the complexity of monocarboxylate transport in the intestinal tract, re-
searchers have recently confirmed the presence of SMCT1 and SMCT2 in the human
and mouse intestine.
11
,
12
Interestingly, these two transporters have very different ex-
pression patterns along the entire length of the intestinal tract. In mouse, SMCT1
was found to have the most abundant transcript expression in the distal part of the
small intestine, cecum, and colon, whereas SMCT2 mRNA expression was local-
ized exclusively to the proximal region of the small intestine.
10
,
12
The presence of
SMCT2 in the proximal (sterile portion) of the small intestine implies that it may play
a major role in the absorption of monocarboxylates that stem from dietary sources
rather than from bacterial sources as in the more distal portions of the intestine.
12
In
addition to assisting the H
+
- linked MCTs in nutrient uptake, the presence of SMCTs
in the colon also presents a unique means by which the intestinal epithelial cell can
import D-lactate from the lumen. Although humans cannot produce D-lactate, it is
the metabolic by-product of many bacteria in the intestinal tract and can serve as an
energy source for mammalian tissues.
10
In situ hybridization studies have also identified unique expression patterns of
SMCTs in the mouse kidney. SMCT2 expression was shown to be greatest in the
cortical regions of the proximal tubule epithelium, where concentrations of lactate
are highest, while SMCT1 transcript expression is high in the cortex and moderate in
medullary regions of the tubule epithelium, where lactate concentrations are low.
12
,
27
Furthermore, the identification of SMCTs in the nephritic proximal tubule epithelium
is significant because no known H
+
-linked MCT has been shown to be expressed on
the apical surface of the proximal or distal region of the tubule epithelium. The SMCTs
would then facilitate the movement of monocarboxylates into and out of the nephron
tubule lumen. It is known that
95% of blood lactate is recovered in the kidney.
28
It makes sense, then, that both high- and low-affinity sodium-coupled cotransporters
are expressed in the proximal tubule, whereas only the high-affinity transporter is
expressed in the distal nephron. During intense exercise the concentration of lactate
in blood can become elevated. The presence of the low-affinity SMCT will ensure
efficient capture of lactate from the blood filtrate, while the high-affinity transporter
will capture the remaining lactate during its passage through the distal nephron.
∼
7.3. REGULATION OF GENE EXPRESSION AND ACTIVITY
7.3.1. Regulation of Gene Expression
Most studies on the regulation of MCT gene expression focus on MCT1. Experimental
evidence suggests that MCT1 function may be regulated at both the transcription and
translational levels. The availability of substrate has been demonstrated to influence
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