The monocarboxylate transporter family--Structure and functional characterization.
Level 5 - mechanism / opinion, no new human data
Narrative review of biochemical and structural mechanistic studies.
PubMed 22131303 · doi:10.1002/iub.573
What was done
This narrative review summarizes structural and biochemical findings on the 14-member monocarboxylate transporter (MCT / SLC16) family. It details the structural topology, catalytic mechanisms, and chaperone protein requirements of monocarboxylate-transporting isoforms (MCT1–4) derived from labeling studies, proteolytic digestion, site-directed mutagenesis, and molecular modeling.
What was found
The abstract reports qualitative mechanistic properties rather than numerical data. MCTs 1–4 facilitate proton-linked transport of L-lactate, pyruvate, and ketone bodies. Structural mapping confirms a 12-transmembrane helix topology with intracellular termini and a large intracellular loop between helices 6 and 7. Proper plasma membrane translocation and catalytic activity of MCT1–4 require association with single-transmembrane immunoglobulin chaperones: MCT1, MCT3, and MCT4 bind preferentially to basigin, whereas MCT2 binds to embigin. Chaperone association alters inhibitor specificity but does not modify substrate kinetics.
Why it matters
Understanding the structural conformations and required chaperone interactions of MCTs provides a mechanistic baseline for targeting cellular metabolic transport (such as lactate shuttling) in disease states.
Limits
The abstract provides no quantitative metrics or statistical evaluations. Findings reflect in vitro biochemical and structural models rather than clinical trial data, and eight of the 14 SLC16 family members remained uncharacterized orphan transporters at the time of review.
Cited by
- supports Ketones and lactate are transported across cell membranes via monocarboxylate transporters (MCTs).