Pantothenate biochemical activities

Phosphopantetheine coenzymes are the biochemically active forms of the vitamin pantothenic acid. In figure 10.11, 4 -phosphopantetheine is shown as covalently linked to an adenylyl group in coenzyme A or it can also be linked to a protein such as a serine hydroxyl group in acyl carrier protein (ACP). It is also found bonded to proteins that catalyze the activation and polymerization of amino acids to polypeptide antibiotics. Coenzyme A was discovered, purified, and structurally characterized by Fritz Lipmann and colleagues in work for which Lipmann was awarded the Nobel Prize in 1953. 

The biochemical mode of action of dalapon has not been unequivocally elucidated. The protein precipitating action of chlorinated aliphatic acids, hence of dalapon, is known (Redemann and Hamaker, 1954), and it has also been proved by the investigations of Kemp et al. (1969) that the acid form of dalapon is able to form a hydrogen bond with the amide group of the protein molecule, so that this mechanism, in blocking enzyme activity, may be the cause of the phytotoxic action. Hilton et al. (1959) proved that dalapon inhibits the pantothenic acid synthesis of plants. 

A pantothenic acid hydrolase (pantothenase) activity has been isolated from Pseudomonas fluorescens and other Pseudomonas strains. This enzyme hydrolyzes the amide bond of pantothenic acid 2 to form pantoic acid 5 (or pantoyl lactone) and /i-alanine 7 (EC 3.5.1.22) (Equation (10)). A detailed kinetic study of the reaction mechanism has shown that the reaction is partially reversible because of the formation of an acyl—enzyme (pantoyl-enzyme) intermediate during the course of catalysis, which may react with either water or / -alanine to form pantoic acid (the product hydrolysis) or pantothenic acid (the original substrate) Such a mechanism suggests that this enzyme could act as a pantothenate synthase, as reaction of the active site serine with pantoyl lactone would result in the formation of the pantoyl—enzyme intermediate. However, no biochemical or genetic evidence is currently available to support such a hypothesis. 

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. 

The 2-carbon unit or activated acetate, which is the acetylated form of coenzyme A, the pantothenic acid-containing enzyme, has been shown to occupy a central position in many converging pathways. The role of mitochondria and other essential cellular units in oxidative metabolism, which have been elucidated recently, link cytology and biochemistry closely together and may lead to closer correlation between pathologic anatomical changes demonstrable in tissue section and biochemical abnormalities found in body fluids and tissues (Chapter 12). 

The sulfur content in the human body is about 140 g. Foods contain a large number of covalent sulfur compounds. Many sulfur compounds perform important biochemical functions as biocatalysts (e.g. thiamine, pantothenic acid bound in coenzyme A and biotin), and sulfur-containing amino acids, cysteine and methionine, are protein constituents. Many sulfur compounds are important precursors of flavour-active compounds. 

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