Disease relevance of ACLY

• As a citrate cleavage enzyme that may play an essential role in de novo lipogenesis inhibition, G cambogia is claimed to lower body weight and reduce fat mass in humans [1].
• PATIENTS AND METHODS: The total series included 102 cases with small-cell carcinoma (SCLC; 40%), adenocarcinoma (ACL; 26%), squamous cell carcinoma (SQLC; 18%) and large-cell carcinoma (LCC; 9%) [2].
• The presence of antibodies to cardiolipin (ACL Abs) has been reported in some patients suffering from multiple sclerosis (MS), especially of the "neuromyelitic" type [3].
• ACL promoter activity was markedly stimulated by the overexpression of SREBP-1a and, to a lesser extent, by SREBP-2 in Alexander human hepatoma cells [4].
• This is due, at least in part, to increases in cytosolic citrate metabolism through ATP citrate lyase in rats similar to that seen with chronic metabolic acidosis and hypokalemia [5].

Psychiatry related information on ACLY

• We hypothesized that a derotational knee brace improved the stability of an ACL deficient knee by augmenting limb proprioception, causing hamstring muscles to increase in activity and/or to contract earlier during a side-step cut [6].
• Results of a 21 question survey, taken at the ACL Study Group meeting in 1984, present a composite picture of current practices in ACL reconstruction and rehabilitation [7].
• ACL research retreat: the gender bias. April 6-7, 2001. Meeting report and abstracts [8].
• We have also briefly outlined the variables that we consider to be the most important in the decision-making process of treatment options after ACL disruption [9].
• Unfortunately, young patients with active life-styles who present with an ACL-deficient knee and early evidence of arthritis remain a very difficult population to treat [10].

High impact information on ACLY

• In this article, we demonstrate that Huh-7 cells harboring replicating, full-length HCV RNAs express elevated levels of ATP citrate lyase and acetyl-CoA synthetase genes, both of which are involved in cholesterol and fatty acid biosynthesis [11].
• The rates of phosphorylation of ATP-citrate lyase by nm23-H1(S120G) and nm23-H1(P96S) were similar to that by wild-type nm23-H1 [12].
• Nm23-H1 also can transfer phosphate from its catalytic histidine to histidines on ATP-citrate lyase and succinic thiokinase [12].
• Atenolol, in contrast, did not affect either TPR or ACL [13].
• Nifedipine reduced total peripheral resistance (TPR; 1744 +/- 398 versus 1290 +/- 215 dyne-s/cm5) and increased arterial compliance (ACL; 1.234 +/- 0.253 versus 1.776 +/- 0.415 mL/mm Hg) [13].

Chemical compound and disease context of ACLY

• However, similar to metabolic acidosis and hypokalemia, enalapril caused a 42% increase in renal cortical ATP citrate lyase activity [5].
• Hydroxycitrate (HCA), a popular dietary supplement for weight loss, is a competitive inhibitor of ATP-citrate lyase, an extramitochondrial enzyme involved in the initial steps of de novo lipogenesis (DNL) [14].
• Clinical analysis was performed on anti-cardiolipin x beta2 glycoprotein 1 (ACL x beta2 GP1) antibody positive patients with collagen vascular diseases [15].
• Cutaneous leishmaniasis caused by Leishmania major (zoonotic, ZCL) and L. tropica (anthroponotic, ACL) is found in most countries of the Eastern Mediterranean Region [16].
• Anaemia was seen in 50.8%, leukopenia in 18.4%, thrombocytopenia in 11.8%, ANA in 100%, anti-dsDNA in 92.3%, anti-Sm in 34.7%, anti-SSA in 38.5%, anti-SSB in 15.4%, ACL in 30.8%, low C3 in 50% and false positive VDRL in 3.3% [17].

Biological context of ACLY

• Localization of the gene for ATP citrate lyase (ACLY) distal to gastrin(GAS) and proximal to D17S856 on chromosome 17q12-q21 [18].
• The gene encoding ATP-citrate lyase, designated ACLY, was mapped to human chromosome 17q12-q21 by PCR on a panel of human/rodent somatic cell hybrids and localized to 17q21.1 by PCR on a panel of radiation hybrids [18].
• A full-length cDNA clone of 4.3 kb encoding the human ATP-citrate lyase enzyme has been isolated by screening a human cDNA library with the recently isolated rat ATP-citrate lyase cDNA clone [Elshourbagy et al. (1990) J. Biol. Chem. 265, 1430] [19].
• Activities of ATPCL and PDH, acetyl-CoA content, and thrombin-evoked MDA synthesis as well as platelet aggregation in diabetes were 31%, 51%, 62%, 35%, and 21%, respectively, higher than in healthy subjects [20].
• DNMT and ACLY were not previously known in cattle, but the physical localization of the cloned bovine exons is in agreement with the published comparative human and bovine maps [21].

Anatomical context of ACLY

• These data indicate preferential localization of ATP-citrate lyase in cholinergic nerve endings, and indicate that this enzyme is not a rate limiting step in the synthesis of the acetyl moiety of ACh in brain [22].
• Over 70% of the activities of both choline acetyltransferase and ATP-citrate lyase in secondary fractions are found in synaptosomes [22].
• Transfected COS cells expressed detectable levels of an enzymatically active recombinant ATP-citrate lyase enzyme [19].
• Stable, amplified expression of ATP-citrate lyase in CHO cells as achieved by using coamplification with dihydrofolate reductase [19].
• ATP citrate lyase in human adipose tissue [23].

Associations of ACLY with chemical compounds

• Regional and subcellular distribution of ATP-citrate lyase and other enzymes of acetyl-CoA metabolism in rat brain [22].
• Since catalysis of ATP-citrate lyase is postulated to involve the formation of phosphohistidine, these results are consistent with the pattern of earlier observations of the significance of the histidine residue in catalysis of the human ATP-citrate lyase [19].
• ATP:citrate lyase (ACL) is a major generator of cytosolic acetyl-coenzymeA, which is required for both fatty acid and cholesterol biosynthesis [24].
• Propranolol also failed to reverse the isoproterenol-induced increased phosphorylation of ATP citrate-lyase specifically [25].
• Sequence of sites on ATP-citrate lyase and phosphatase inhibitor 2 phosphorylated by multifunctional protein kinase (a glycogen synthase kinase 3 like kinase) [26].

Other interactions of ACLY

• The normal activity of glucose-6-phosphate dehydrogenase and malate dehydrogenase (decarboxylating) (NADP), which supply NADPH for the reduction of acetyl-CoA to fatty acids, would suggest that the change in lipogenesis is of moderate degree, thereb) affecting only the most rate-limiting enzyme, ATP citrate-lyase [27].
• By monitoring the appearance of a known cytosolic protein (ATP citrate lyase) in the medium, we find that the unmodified IL-1 beta s are non-specifically released in very small quantities from the cytosol [28].
• While fatty acid synthase is further established as a target for antineoplastic intervention, recent findings show that interference with acetyl-CoA carboxylase-alpha, ATP citrate lyase or the AMP-activated protein kinase limits cancer cell proliferation and survival [29].
• The increase in lipogenic rate is exactly parallel to a coordinate rise in the activities of the key enzymes of the fatty acid biosynthetic pathway (ATP-citrate lyase, acetyl-CoA carboxylase, and fatty acid synthetase) [30].
• Three of the citrate-processing enzymes, citrate synthase, ATP citrate lyase, and citrate lyase, catalyze reversible aldol-type condensations [31].

Analytical, diagnostic and therapeutic context of ACLY

• Site-specific mutagenesis of His765----Ala diminishes the catalytic activity of the expressed ATP-citrate lyase protein [19].
• The recombinant protein (re-hACL) was purified to homogeneity from the soluble lysate of infected cells and was observed to exist as a tetramer by gel filtration chromatography [24].
• The human ACL (hACL) cDNA was cloned by RT-PCR, and our results indicate the existence of previously unknown sequence variations in hACL [24].
• It is demonstrated that the beta-adrenergic agonist isoproterenol or insulin both promote an immobilization of ATP citrate-lyase, detected in digitonin-permeabilized adipocytes [25].
• The identity of the 120-kDa protein as ATP citrate lyase was confirmed by immunoblotting [32].

References