Pantothenic acid turnover

Attachment of phosphopantetheine to proteins is catalyzed by a phosphotransferase that utilizes CoA as the donor. A phosphodiesterase removes the phosphopantetheine, providing a turnover cycle.15, 5b A variety of synthetic analogs have been made.4 16 The reactive center of CoA and phosphopantetheine is the SH group, which is carried on a flexible arm that consists in part of the (3-alanine portion of pantothenic acid. A mystery is why pantoic acid, a small odd-shaped molecule that the human body cannot make, is so essential for life. The hydroxyl group is a potential reactive site and the two methyl groups may enter into formation of a "trialkyl lock" (p. 485), part of a sophisticated "elbow" or shoulder for the SH-bearing arm. 

It is apparent that at this stage of development definitive conclusions are premature, and that this aspect of amino acid and lipide metabolism will be pursued vigorously in the near future. It is of considerable interest to us that biotin and pantothenic acid deficiencies affect amino acid transport in L. arabinosus, since both vitamins are known to play a prominent role in lipide biosynthesis. We are currently reexamining the turnover of lipide fractions in nutritionally normal and vitamin-deficient cell types to determine whether there is some relation between this aspect of metabolism and amino acid transport. In any case, the nature of the catalytic steps involved in amino acid transport is still unknown to us. They probably occur in the peripheral cell membrane, but even this elementary and widely accepted belief will require additional study before it can be accepted beyond doubt as an established fact. 

These findings can be interpreted to support a concept of pool formation in which free amino acids accumulate within the cell through the intervention of membrane-localized transport catalysts. The nature of these catalysts is still unknown. The kinetic and osmotic experiments reported here also appear to exclude biotin and pantothenic acid from direct involvement in the transport process. The evidence suggests that like vitamin B6 they affect transport indirectly through some change in the synthesis or turnover of a structural component of the cell. 

Conventional metabolic pathway engineering concepts and tools were appropriate to develop B. suhtilis Marburg 168 into efficient production strains for the vitamins riboflavin and pantothenic acid. For both compounds, the biochemical reactions from common metabolites to the final products were known to a great detail. Pantothenic acid biosynthesis involves efficient enzymes with high turnover numbers that catalyze standard biochemical reactions. The enzymes of the riboflavin pathway catalyzing more complex reactions are relatively slow, but strains overexpressing these enzymes could be furnished with sufficient biocat-alytic activity. 

One application of this hydrogenation with the structurally related 4,4-dimethyl-2, 3-furandione is shown in Equation 15.53. This a-ketoester undergoes hydrogenation with a neutral rhodium catalyst containing the bpm ligand shown in this equation with spectacularly high turnover numbers and good enantioselectivity. This product is used by Roche in the synthesis of pantothenic acid, a B-vitamin used for the synthesis of coenzyme... 

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