The Absorption of Beta-Carotene and Its Conversion into Vitamin A

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Abstract
The final diagram24 (Fig. 6) may be used to summarize our present thoughts on this subject. β-Carotene is absorbed from the intestine and is converted into vitamin A only in the presence of bile acids. Conjugated bile acids do not function solely in dispersing the lipophilic substrate into a micellar form which is suitable for absorption. Rather, they possess a more specific function which is lodged mainly in the cholanic acid structure, but is enhanced by conjugation. Cholic acid derivatives were most effect in stimulating the overall conversion. The presence of a negative charge or of an N-acyl glycine derivative in the micelle did not in itself enhance β-carotene cleavage. Since the uptake of vitamin A alcohol, retinene, and apparently of vitamin A acid was unaffected by conjugated bile acids, and since no apparent stimulation of intracellular synthetic reactions took place in their presence, it is likely that the bile salts act primarily by enhancing the absorption of β-carotene rather than by stimulating β-carotene cleavage. The action of bile salts in molecular terms, however, is completely unknown. The rate limiting step in the over-all conversion process also seems to reside at the absorptive step. If correction is made for the β-carotene bound nonspecifically—a binding which is independent of oxygen, occurs rapidly, and increases as the integrity of the intestinal preparation declines—the calculated amount of intracellular β-carotene is very low. Furthermore, the rate of uptake and esterification of vitamin A alcohol and of retinene is rapid compared to the rate of β-carotene conversion. Few intermediates accumulate between β-carotene and vitamin A ester. Some retinene and vitamin A alcohol are present, and some nonpolar and acidic products form. The amount of these is small, however, compared to the amount of ester present; and there is no reason to believe that the acidic and polar compounds are intermediates of β-carotene cleavage. Indeed, no real evidence exists that retinene is a direct intermediate, although it is present in the intestine, reaches a maximal concentration early, and is converted to vitamin A ester. The requirement for oxygen may be involved in absorption, cleavage, or in the general maintenance of the tissue. With reservations, a central cleavage mechanism seems to be favored by our results. A more detailed possible mechanism is outlined in Figure 6, based in large part on analogous reactions carried out by known enzyme systems. Only the reduction of retinene and esterification of vitamin A have been demonstrated thus far in cell free systems. Finally, the rise in vitamin A ester to a maximum followed by a decrease suggests that the formation of lipoprotein and its secretion into the lymph is a second rate-limiting step.