Transfer across Perfused Human Placenta. IV. Effect of Protein Binding on Free Fatty Acids

Extract: The effect of protein binding on the rate of placental transfer of hexanoic (C 6) and decanoic (C 10) acids was investigated in an in vitro perfusion system of human placenta. As

much as 30% of transferred C 6 was converted to more polar compounds; so that the observations related to the combined effects on transfer and metabolism. Less than 10% of C 10 was similarly

metabolized. Both fatty acids are soluble in buffered salt solutions at the concentrations used (40 μM) and both are bound to serum albumin, C-10 having higher association constants (K′ for

C 6, 1.48 × 104; for C 10, 1.03 × 105). When the placenta is perfused with buffered salt solution, the transfer of C 6 is 22% more rapid than that of C 10. It is suggested that binding

within the placenta retards C 10 more than C 6. The addition of 1 g/100 ml bovine serum albumin to the maternal perfusate reduces the transfer rate of C 10 by 80%, whereas 2 g/100 ml serum

albumin has a more moderate effect on C 6 (a reduction of 50%). The addition of 1 g/100 ml serum albumin to the fetal perfusate increases transfer rate of both free fatty acids (FFA), C 6 by

about 25% and C 10 by about 250%. With equivalent concentrations of serum albumin in maternal and fetal perfusates, the transfer rate of C 10 was reduced by 65%, whereas there was no

detectable effect on transfer of C 6 in two of three experiments.

The transfer rates of FFA increase logarithmically with progressive shortening of the carbon chain from C 16 to C 8 when maternal and fetal perfusates contain serum albumin. Protein binding

is apparently the determining factor. The rate of transfer falls off at C 6 and C 4, even though protein-binding continues to decrease. The determining factor may be the hydrophilic nature

of these molecules.

Speculation: If the observations on FFA have general applicability, the overall effect of protein binding on placental transfer of a particular substance may relate to its water solubility

and protein binding. If water solubility is not a limiting factor, protein binding may decrease transfer rate sharply, as occurs with decanoic acid (C 10). With substances that have very

limited water solubility, protein binding may increase transfer by increasing the amount presented to the placenta. Palmitic acid (C 16) appears to be such a compound. The fraction bound to

proteins in the perfusate, as measured by equilibrium dialysis, may not be the most significant factor determining rates of transfer. More significant may be the competitive aspects of

binding in the perfusate and to the placenta in influencing rates of release and uptake.

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