Uptake of oleate from albumin solutions by rat liver. Failure to detect catalysis of the dissociation of oleate from albumin by an albumin receptor.

Abstract

The hepatic removal of albumin-bound substances from plasma requires that they dissociate from albumin. Using indirect methods, we and others have proposed that dissociation may be catalyzed by interaction of albumin with the liver cell surface. This study looked for direct evidence of catalysis by comparing the rate of dissociation of oleate from albumin in vitro with the rate observed within the sinusoids of perfused rat liver. No evidence for catalysis was found. The rate of hepatic oleate removal from dilute albumin solutions did not exceed but instead closely paralleled the rate predicted from the in vitro dissociation rate constant (0.14 s-'). These results suggest that under some conditions the liver can remove unbound material from the sinusoids faster than it can be replenished by dissociation from albumin, resulting in dissociation-limited removal. However, dissociation of oleate does not appear to be catalyzed by the liver.

Hepatic oleate uptake. Electrochemical driving forces in intact rat liver.

“…We have recently argued that uptake of fatty acids requires that they first enter the unbound pool by spontaneous dissociation from albumin, and have shown that at lower albumin concentrations dissociation may limit the uptake rate by limit- ing the availability of unbound fatty acid within the hepatic sinusoids (5). Because unbound fatty acids make up < 0.02% of the total fatty acid in plasma, such a sequence requires an extraordinarily efficient cellular mechanism for removing unbound fatty acids from the sinusoids.…”

“…Hepatic uptake of unesterified fatty acids from plasma proceeds rapidly despite binding of > 99.98% of plasma fatty acids to serum albumin. It has been suggested that this high efficiency reflects a direct interaction ofthe albumin-fatty acid complex with the liver cell membrane (2-4), although we no longer favor this view (5). On the other hand, the uptake mechanism would need to be extraordinarily efficient to account for observed uptake rates if cellular uptake draws only on the small unbound fatty acid pool in plasma (3).…”

Fatty acid uptake in normal human myocardium.

“…Therefore, the FA dissociation from albumin is commonly not thought to be a rate-limiting step for FA transport into myocardial tissue. [20][21][22] The transfer of FA from plasma to cardiac cells does not involve solely a phase boundary (plasmacapillary wall) process; it also involves a sequence of membrane and aqueous phase translocation processes. These include passage of FAs across the capillary wall and movement through the intercellular space before they are presented to the cardiomyocytes.…”

Evidence for vesicles that mediate long-chain fatty acid uptake by human microvascular endothelial cells

“…As most tissues have limited or no capacity to synthesize LCFA on their own, they depend on LCFA uptake from the circulation. Both the liver and the heart are extremely efficient in extracting LCFA from the blood (1,4). The endothelial layer is the first barrier to be traversed by LCFA before they can be metabolized by the underlying parenchymal tissue.…”