Fat cadherins constitute a subclass of the large cadherin family characterized by the presence of 34 cadherin motifs. To date, three mammalian Fat cadherins have been described; however, only limited information is known about the function of these molecules. In this paper, we describe the second fat cadherin in Drosophila, fat-like (ftl). We show that ftl is the true orthologue of vertebrate fat-like genes, whereas the previously characterized tumor suppressor cadherin, fat, is more distantly related as compared with ftl. Ftl is a large molecule of 4705 amino acids. It is expressed apically in luminal tissues such as trachea, salivary glands, proventriculus, and hindgut. Silencing of ftl results in the collapse of tracheal epithelia giving rise to breaks, deletions, and sac-like structures. Other tubular organs such as proventriculus, salivary glands, and hindgut are also malformed or missing. These data suggest that Ftl is required for morphogenesis and maintenance of tubular structures of ectodermal origin and underline its similarity in function to a reported lethal mouse knock-out of fat1 where glomerular epithelial processes collapse. Based on our results, we propose a model where Ftl acts as a spacer to keep tubular epithelia apart rather than the previously described adhesive properties of the cadherin superfamily.
The substrates required for glycolysis change markedly at successive stages of spermatogenesis suggesting a considerable plasticity in the expression of glycolytic enzymes. Lactate dehydrogenase (LDH) isoenzymes, LDH-A and LDH-B, are expressed in premeiotic, meiotic cells, and early spermatids, both in avian and mammalian spermatogenesis. Highly polyadenylated forms, particularly of LDH-A, were detected in chicken testis. While mammals and columbid birds express the testis specific LDH-C gene in meiotic and postmeiotic cells, several LDH-B testis specific transcripts were detected in the corresponding cells during chicken spermatogenesis. These testis specific transcripts and the mRNA of mammalian LDH-C show several properties in common, such as temporal correlation of expression, mRNA stability, and repression of premature translation. These observations suggest that the testis specific transcripts could perform during chicken spermatogenesis the functions of the LDH-C mRNA in mammalian testis.
Theoretical and experimental evidence is presented which leads to a rejection of the proposal that the transient-state kinetics of the coupled two-enzyme reaction involving aldolase and glyceraldehyde-3-phosphate dehydrogenase are indicative of a channelled transfer of glyceraldehyde 3-phosphate from the producing enzyme to the consuming one.Keywords: channelling ; transient-state kinetics ; glycolytic enzymes.The possible existence of metabolite channelling between enzymes participating in consecutive reactions of the glycolytic pathway has been a matter of much dispute [l]. One of the proposed biological advantages of metabolite channelling is that it might lead to a reduction of transient times in metabolic systems [I -41, i.e. a reduction of the rate at which steady-state conditions are restored following perturbations of the system. Evidence that claimed to indicate such a reduction of transient times for consecutive enzymes in the glycolytic pathway has been presented by Orosz and Ovidi [5]. They found that the transient rate of N A D H production due to the catalytic interaction of glyceraldehyde-3-phosphate dehydrogenase with glyceraldehyde 3-phosphate increases drastically when the substrate is produced in a coupled reaction through the action of aldolase on fructose 1,6-bisphosphate. This led them to propose that the observed rate increase derives from a channelled transfer of glyceraldehyde 3-phosphate from aldolase to the dehydrogenase.The proposal of Orosz and Ovidi [S] was based on the supposition that the examined transients exhibiting distinct rates reflect comparable mechanistic events. In this investigation, we present evidence showing that this is not the case. Adequately interpreted results of Orosz and Ovidi (and those now presented) infer that the transient-state kinetics of the coupled reaction involving aldolase and glyceraldehyde-3-phosphate dehydrogenase are fully consistent with a free-diffusion mechanism of metabolite transfer and cannot be reconciled with a mechanism of metabolite channelling. THEORYBasic transient-state kinetic relationships for the examined reaction system. Let us consider the irreversible conversion of a substrate S into a product P through the action of an enzyme E operating under pseudo first-order conditions with an apparent first-order rate constant k. The substrate is assumed to be present in two interconvertible forms, one of which (S*) does not interact with the enzyme. The catalytically reactive form (S)Corresponderice to G. Pettersson, Department of Biochemistry, Fax: +46 40 156418.Chemical Center, Box 124, S-221 00 Lund, Sweden of the substrate is further assumed to be produced from an external source at a constant rate u which may or may not equal zero.The kinetic scheme for such a reaction system may be written as 5 s k . p(1)11 k-j S* and prescribes that ( 2 )This set of linear differential equations can be analytically solved. The solution for [S] is given bywhere A, and A, (IL2 3 2,) are the two roots of the secular equa-If k 9 k -, 9 k,, one has I...
Steady-state and transient-state kinetic experiments have been performed to test the proposal that there is a direct (channelled) transfer of NADH from glyceraldehyde-3-phosphate dehydrogenase to alcohol dehydrogenase. The results lend no support to this proposal, but can be best explained in terms of a freediffusion mechanism for NADH transfer between the two enzymes.Keywords: enzyme kinetics ; channeling ; dehydrogenase.Srivastava and Bernhard in 1984 reported that transfer of the coenzyme NADH from glyceraldehyde-3-phosphate dehydrogenase to alcohol dehydrogenase not only proceeds by the freediffusion mechanism shown in Scheme 1, but also by a mechanism of channelled coenzyme transfer [l]. The evidence leading to this conclusion came from steady-state kinetic measurements indicating that the reduction of aldehydes, catalysed by liver alcohol dehydrogenase, was faster than expected for a free-diffusion mechanism of NADH transfer when reactions were performed in the presence of very high concentrations of halibut glyceraldehyde-3-phosphate dehydrogenase. This was claimed to show that the binary complex of NADH and glyceraldehyde-3-phosphate dehydrogenase may substitute for NADH as a coenzyme in the alcohol-dehydrogenase-catalysed reduction of aldehydes, such that there is a direct transfer of NADH from one enzyme to the other without prior release of the coenzyme to solution (Scheme 2).Many kinetically based claims for the existence of a direct (channelled) metabolite transfer between enzymes that do not form static multi-enzyme complexes have been found to derive from misinterpretations of the experimental data [2-61. Considering this and the general importance of establishing by what mechanisms metabolites may be transferred in metabolic pathways, we have reinvestigated the case of NADH transfer between alcohol dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The results are inconsistent with the conclusions drawn by Srivastava and Bernhard [l] and provide evidence that the transfer of NADH between the two enzymes proceeds by a mechanism of free diffusion without any detectable contributions from metabolite channelling.
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