Utilization of biotin in proliferating human lymphocytes

Area of Science:

• Immunology
• Cell Biology
• Nutritional Biochemistry

Background:

• Lymphocytes are key immune cells that proliferate upon antigenic stimulation.
• Understanding nutrient transport in activated immune cells is crucial for immune function.
• Biotin is an essential vitamin involved in various metabolic processes.

Purpose of the Study:

• To investigate if proliferating lymphocytes enhance biotin cellular uptake.
• To elucidate the mechanisms behind increased biotin uptake in stimulated lymphocytes.
• To determine if increased biotin uptake supports metabolic demands of proliferating lymphocytes.

Main Methods:

• Human peripheral blood lymphocytes were isolated and stimulated to proliferate using mitogens (pokeweed lectin, concanavalin A, phytohemagglutinin).
• Biotin uptake was quantified using radiolabeled [3H]biotin, with confirmation of minimal biotin metabolism.
• Kinetic analysis and the effect of cycloheximide (protein synthesis inhibitor) were assessed.

Main Results:

• Biotin uptake increased by 278-722% in proliferating lymphocytes compared to non-proliferating controls.
• The increase in uptake was attributed to a higher number of biotin transporters on the cell surface, not altered affinity.
• Inhibition of protein synthesis abolished the mitogen-induced increase in biotin transport.
• Biotin-dependent beta-methylcrotonyl-CoA carboxylase activity was 2.5-fold higher in stimulated lymphocytes.

Conclusions:

• Mitogen-stimulated lymphocytes increase biotin uptake primarily by upregulating the synthesis of biotin transporters.
• This enhanced uptake likely provides necessary biotin coenzyme for increased carboxylase activity in proliferating immune cells.
• The findings highlight a specific nutrient transport adaptation in activated lymphocytes to meet metabolic demands.