Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo.

Extracellular hydrolysis of the phosphate esters of B vitamins (B1, B2, and B6) is crucial for their cellular uptake and metabolism. Although a few zinc-dependent enzymes have been implicated in these processes, their exact mechanisms of action remain largely unknown. This study investigated the potential involvement of phosphate group hydrolyzing enzymes in the hydrolysis of B vitamin phosphate esters.

ZNT5-6 and ZNT7 play an integral role in protein N-glycosylation by supplying Zn to Golgi α-mannosidase II.

The stepwise addition of monosaccharides to N-glycans attached to client proteins to generate a repertoire of mature proteins involves a concerted action of many glycosidases and glycosyltransferases. Here, we report that Golgi α-mannosidase II (GMII), a pivotal enzyme catalyzing the first step in the conversion of hybrid- to complex-type N-glycans, is activated by Zn supplied by the early secretory compartment-resident ZNT5-ZNT6 heterodimers (ZNT5-6) and ZNT7 homodimers (ZNT7). Loss of ZNT5-6 and ZNT7 function results in marked accumulation of hybrid-type and complex/hybrid glycans with concomitant reduction of complex- and high-mannose-type glycans.

Sophisticated expression responses of ZNT1 and MT in response to changes in the expression of ZIPs.

The zinc homeostatic proteins Zn transporter 1 (ZNT1) and metallothionein (MT) function in dampening increases in cytosolic zinc concentrations. Conversely, the expression of ZNT1 and MT is expected to be suppressed during decreases in cytosolic zinc concentrations. Thus, ZNT1/MT homeostatic responses are considered to be essential for maintaining cellular zinc homeostasis because cellular zinc concentrations are readily altered by changes in the expression of several Zrt-/Irt-like proteins (ZIPs) under both physiological and pathological conditions.

Early secretory pathway-resident Zn transporter proteins contribute to cellular sphingolipid metabolism through activation of sphingomyelin phosphodiesterase 1.

Sphingomyelin phosphodiesterase 1 (SMPD1) converts sphingomyelin into ceramide and phosphocholine; hence, loss of SMPD1 function causes abnormal accumulation of sphingomyelin in lysosomes, which results in the lipid-storage disorder Niemann-Pick disease (types A and B). SMPD1 activity is dependent on zinc, which is coordinated at the active site of the enzyme, and although SMPD1 has been suggested to acquire zinc at the sites where the enzyme is localized, precisely how SMPD1 acquires zinc remains to be clarified. Here, we addressed this using a gene-disruption/reexpression strategy.