Specifically, very long chain acylcoenzyme A (CoA) dehydrogenase (VLCAD), medium chain acyl-CoA dehydrogenase (MCAD), peroxisomal bifunctional protein (hydratase
+ 3-hydroxyacyl-CoA dehydrogenase) (PH), peroxisomal thiolase (PT), diacylglicerol acyltransferase 1 (DGAT1), and p52 mRNA levels were higher in hPPAR[alpha] mice than in mPPAR[alpha] and Ppar[alpha]-null mice.
MLST was performed by using the following seven housekeeping genes (protein products are shown in parentheses): abcZ (putative ATP-binding cassette transporter), adk (adenylate kinase), aroE (shikimate dehydrogenase), fumC (fumarate hydratase
) gdh (glucose-6-phosphate dehydrogenase), pdhC (pyruvate dehydrogenase subunit), and pgm (phosphoglucomutase) as previously described (6).
The teams pooled their efforts and report in an upcoming issue of Nature Genetics the discovery of mutations of the gene that encodes an enzyme called fumarate hydratase
. Previous research had shown that this enzyme normally enables a cell to derive energy by metabolizing sugar.
patent application number 08/873,001, 'Transformation of Wheat with the Cyanamide Hydratase
Gene,' contact J.
(ACOH, EC 22.214.171.124 [two loci]), Adenylate Kinase (AK, EC 126.96.36.199), Arginine Kinase (ARK, EC 188.8.131.52), Dihydrolipoamide Dehydrogenase (DDH, EC 184.108.40.206 [two loci, only one scorable]), Glucose-6-phosphate Isomerase (GPI, EC 220.127.116.11), Malate Dehydrogenase (MDH, EC 18.104.22.168 [two loci, only one scorable]), Phosphogluconate Dehydrogenase (PGDH, EC 22.214.171.124), and Phosphoglucomutase (PGM, EC 126.96.36.199) were resolved on a discontinuous tris-citrate buffer pH 7.1 (Ayala et al.
Other, less intuitive ones include Enoyl-CoA hydratase
1 (ECH1), which is associated with fatty acid metabolism, and complement C1q binding protein (C1QBP), associated with immune function.
Type I 3-MGAuria is caused by defective activity of 3-MG-CoA hydratase
within the leucine catabolic pathway, and is known as "primary 3-MGA-uria." Barth syndrome (type II) is an example of "secondary 3-MGA-uria" associated with normal hydratase
activity and unaffected leucine catabolism.
Interestingly, inhibition of LDH-A, a major isoform of LDH and a known HIF target which is overexpressed in RCC, has been recently shown to suppress the tumouregenesis of cells that underexpress fumarate hydratase
(FH) both in vitro and in vivo.[sup.13] Inactivation of the FH gene, a key enzyme in the TCA cycle which catalyzes the conversion of fumarate to malate, results in the accumulation of HIF.[sup.14] Although the inhibitory effects of LDH-A inhibition were shown for the smaller subset of type 2 papillary RCC which have a genetic defect in the FH gene (patients with hereditary leiomyomatosis and renal cell cancer- HLRCC), they are probably applicable to the more common type of clear-cell RCC, in which enhanced LDH activity and glycolysis occurs also largely due to HIF activity.
Peroxisomal bifunctional protein from rat liver is a trifunctional enzyme possessing 2-Enoyl-CoA hydratase
, 3-Hydroxyacyl-CoA dehydrogenase, and [[DELTA].sup.3],[[DELTA].sup.2]-Enoyl-CoA isomerase activities.
Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC), also referred to as Reed syndrome, (1-4) is a rare familial cancer disorder caused by a germline mutation in the fumarate hydratase
(FH) gene (Figure 1).
The majority of these expressed proteins were involved in glycolysis (enolase, fructose-bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase, L-lactate dehydrogenase, 6-phosphofructokinase, glucose-6-phosphate isomerase, phosphoglycerate kinase, phosphopyruvate hydratase
, pyruvate kinase, triosephosphate isomerase, and 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase) and the remaining proteins were involved in fer-mentation (alcohol-acetaldehyde dehydrogenase, formate ace-tyltransferase, and pyruvate-formate lyase), the pentose phosphate pathway (6-phosphogluconate dehydrogenase [decarboxylating]), pyruvate decarboxylation (pyruvate dehydrogenase complex E2 component), and the urea cycle (ornithine carbamoyltransferase).
The 3 enzymes involved are long-chain enoyl-CoA hydratase
(LCEH), long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), and long-chain 3-ketoacyl-CoA thiolase (LCTH).