scholarly journals AMP-forming acetyl-CoA synthetases in Archaea show unexpected diversity in substrate utilization

Archaea ◽  
2006 ◽  
Vol 2 (2) ◽  
pp. 95-107 ◽  
Author(s):  
Cheryl Ingram-Smith ◽  
Kerry S. Smith
Keyword(s):  
Phylogenetic Analysis ◽  
Molecular Basis ◽  
Catalytic Efficiency ◽  
Adenosine Monophosphate ◽  
Archaeoglobus Fulgidus ◽  
Acetyl Coa ◽  
Chain Acyl ◽  
Key Enzyme ◽  
Methanothermobacter Thermautotrophicus ◽  
Branched Chain

Adenosine monophosphate (AMP)-forming acetyl-CoA synthetase (ACS; acetate:CoA ligase (AMP-forming), EC 6.2.1.1) is a key enzyme for conversion of acetate to acetyl-CoA, an essential intermediate at the junction of anabolic and catabolic pathways. Phylogenetic analysis of putative short and medium chain acyl-CoA synthetase sequences indicates that the ACSs form a distinct clade from other acyl-CoA synthetases. Within this clade, the archaeal ACSs are not monophyletic and fall into three groups composed of both bacterial and archaeal sequences. Kinetic analysis of two archaeal enzymes, an ACS fromMethanothermobacter thermautotrophicus(designated as MT-ACS1) and an ACS fromArchaeoglobus fulgidus(designated as AF-ACS2), revealed that these enzymes have very different properties. MT-ACS1 has nearly 11-fold higher affinity and 14-fold higher catalytic efficiency with acetate than with propionate, a property shared by most ACSs. However, AF-ACS2 has only 2.3-fold higher affinity and catalytic efficiency with acetate than with propionate. This enzyme has an affinity for propionate that is almost identical to that of MT-ACS1 for acetate and nearly tenfold higher than the affinity of MT-ACS1 for propionate. Furthermore, MT-ACS1 is limited to acetate and propionate as acyl substrates, whereas AF-ACS2 can also utilize longer straight and branched chain acyl substrates. Phylogenetic analysis, sequence alignment and structural modeling suggest a molecular basis for the altered substrate preference and expanded substrate range of AF-ACS2 versus MT-ACS1.

Molecular function of the prolyl cis/trans isomerase and metallochaperone SlyD

2013 ◽  
Vol 394 (8) ◽  
pp. 965-975 ◽  
Author(s):  
Michael Kovermann ◽  
Franz X. Schmid ◽  
Jochen Balbach
Keyword(s):  
Molecular Chaperone ◽  
Molecular Basis ◽  
Catalytic Efficiency ◽  
Enzyme Mechanism ◽  
Molecular Function ◽  
Twin Arginine Translocation ◽  
Chaperone Function ◽  
Nickel Binding ◽  
Biophysical Analysis ◽  
Optimal Function

Abstract SlyD is a bacterial two-domain protein that functions as a molecular chaperone, a prolyl cis/trans isomerase, and a nickel-binding protein. This review summarizes recent findings about the molecular enzyme mechanism of SlyD. The chaperone function located in one domain of SlyD is involved in twin-arginine translocation and increases the catalytic efficiency of the prolyl cis/trans isomerase domain in protein folding by two orders of magnitude. The C-terminal tail of SlyD binds Ni2+ ions and supplies them for the maturation of [NiFe] hydrogenases. A combined biochemical and biophysical analysis revealed the molecular basis of the delicate interplay of the different domains of SlyD for optimal function.

scholarly journals Evidence that ACN1 (acetate non-utilizing 1) prevents carbon leakage from peroxisomes during lipid mobilization in Arabidopsis seedlings

2011 ◽  
Vol 437 (3) ◽  
pp. 505-513 ◽  
Author(s):  
Elizabeth Allen ◽  
Annick Moing ◽  
Jonathan A. D. Wattis ◽  
Tony Larson ◽  
Mickaël Maucourt ◽  
...  
Keyword(s):  
Carbon Sink ◽  
Glyoxylate Cycle ◽  
Eicosenoic Acid ◽  
Primary Metabolism ◽  
Acetyl Coa ◽  
Primary Metabolite ◽  
Lipid Mobilization ◽  
Transcript Levels ◽  
Chain Acyl ◽  
Acetate Accumulation

ACN1 (acetate non-utilizing 1) is a short-chain acyl-CoA synthetase which recycles free acetate to acetyl-CoA in peroxisomes of Arabidopsis. Pulse-chase [2-13C]acetate feeding of the mutant acn1–2 revealed that acetate accumulation and assimilation were no different to that of wild-type, Col-7. However, the lack of acn1–2 led to a decrease of nearly 50% in 13C-labelling of glutamine, a major carbon sink in seedlings, and large decreases in primary metabolite levels. In contrast, acetyl-CoA levels were higher in acn1–2 compared with Col-7. The disappearance of eicosenoic acid was slightly delayed in acn1–2 indicating only a small effect on the rate of lipid breakdown. A comparison of transcript levels in acn1–2 and Col-7 showed that induced genes included a number of metabolic genes and also a large number of signalling-related genes. Genes repressed in the mutant were represented primarily by embryogenesis-related genes. Transcript levels of glyoxylate cycle genes also were lower in acn1–2 than in Col-7. We conclude that deficiency in peroxisomal acetate assimilation comprises only a small proportion of total acetate use, but this affects both primary metabolism and gene expression. We discuss the possibility that ACN1 safeguards against the loss of carbon as acetate from peroxisomes during lipid mobilization.

scholarly journals A Millennial Myosin Census

2001 ◽  
Vol 12 (4) ◽  
pp. 780-794 ◽  
Author(s):  
Jonathan S. Berg ◽  
Bradford C. Powell ◽  
Richard E. Cheney
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Phylogenetic Analysis ◽  
Molecular Basis ◽  
General Interest ◽  
Class Iii ◽  
New Class ◽  
The Past ◽  
Human Genes ◽  
Complete Set ◽  
Myosin Superfamily

The past decade has seen a remarkable explosion in our knowledge of the size and diversity of the myosin superfamily. Since these actin-based motors are candidates to provide the molecular basis for many cellular movements, it is essential that motility researchers be aware of the complete set of myosins in a given organism. The availability of cDNA and/or draft genomic sequences from humans,Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana,Saccharomyces cerevisiae, Schizosaccharomyces pombe, andDictyostelium discoideum has allowed us to tentatively define and compare the sets of myosin genes in these organisms. This analysis has also led to the identification of several putative myosin genes that may be of general interest. In humans, for example, we find a total of 40 known or predicted myosin genes including two new myosins-I, three new class II (conventional) myosins, a second member of the class III/ninaC myosins, a gene similar to the class XV deafness myosin, and a novel myosin sharing at most 33% identity with other members of the superfamily. These myosins are in addition to the recently discovered class XVI myosin with N-terminal ankyrin repeats and two human genes with similarity to the class XVIII PDZ-myosin from mouse. We briefly describe these newly recognized myosins and extend our previous phylogenetic analysis of the myosin superfamily to include a comparison of the complete or nearly complete inventories of myosin genes from several experimentally important organisms.

BCAA Supplementation in Mice with Diet-Induced Obesity Alters the Metabolome Without Impairing Glucose Homeostasis

Endocrinology ◽  
2021 ◽  
Author(s):  
Jennifer Lee ◽  
Archana Vijayakumar ◽  
Phillip J White ◽  
Yuping Xu ◽  
Olga Ilkayeva ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Homeostasis ◽  
Obese Mice ◽  
High Fat ◽  
Leucine Oxidation ◽  
Insulin Resistant ◽  
Diet Induced Obesity ◽  
Chain Acyl ◽  
Branched Chain ◽  
Relationship Of

Abstract Circulating branched chain amino acid (BCAA) levels are elevated in obese humans and genetically obese rodents. However, the relationship of BCAAs to insulin resistance in diet-induced obese mice, a commonly used model to study glucose homeostasis, is still ill-defined. Here we examined how high-fat high-sucrose (HFHS) or high-fat diet (HFD) feeding, with or without BCAA supplementation in water, alters the metabolome in serum/plasma and tissues in mice and whether raising circulating BCAA levels worsens insulin resistance and glucose intolerance. Neither HFHS nor HFD-feeding raised circulating BCAA levels in insulin-resistant diet-induced obese mice. BCAA supplementation raised circulating BCAA and BCKA levels and C5-OH/C3-DC acylcarnitines (AC) in muscle from HFHS or HFD-fed mice, but did not worsen insulin resistance. A set of short and long-chain acyl CoAs were elevated by diet alone in muscle, liver and WAT, but not increased further by BCAA supplementation. HFD feeding reduced valine and leucine oxidation in WAT but not in muscle. BCAA supplementation markedly increased valine oxidation in muscle from HFD-fed mice while leucine oxidation was unaffected by diet or BCAA treatment. Here we establish an extensive metabolome database showing tissue-specific changes in mice on two different HFDs, with or without BCAA supplementation. We conclude that mildly elevating circulating BCAAs and a subset of ACs by BCAA supplementation does not worsen insulin resistance or glucose tolerance in mice. This work highlights major differences in the effects of BCAAs on glucose homeostasis in diet-induced obese mice versus data reported in obese rats and in humans.

scholarly journals ABC Transporter Subfamily D: Distinct Differences in Behavior between ABCD1–3 and ABCD4 in Subcellular Localization, Function, and Human Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kosuke Kawaguchi ◽  
Masashi Morita
Keyword(s):  
Abc Transporters ◽  
Critical Role ◽  
Vitamin B ◽  
Long Chain Fatty Acids ◽  
Substrate Specificities ◽  
Related Disease ◽  
Chain Acyl ◽  
Membrane Bound ◽  
Branched Chain ◽  
Long Chain

ATP-binding cassette (ABC) transporters are one of the largest families of membrane-bound proteins and transport a wide variety of substrates across both extra- and intracellular membranes. They play a critical role in maintaining cellular homeostasis. To date, four ABC transporters belonging to subfamily D have been identified. ABCD1–3 and ABCD4 are localized to peroxisomes and lysosomes, respectively. ABCD1 and ABCD2 are involved in the transport of long and very long chain fatty acids (VLCFA) or their CoA-derivatives into peroxisomes with different substrate specificities, while ABCD3 is involved in the transport of branched chain acyl-CoA into peroxisomes. On the other hand, ABCD4 is deduced to take part in the transport of vitamin B12from lysosomes into the cytosol. It is well known that the dysfunction of ABCD1 results in X-linked adrenoleukodystrophy, a severe neurodegenerative disease. Recently, it is reported that ABCD3 and ABCD4 are responsible for hepatosplenomegaly and vitamin B12deficiency, respectively. In this review, the targeting mechanism and physiological functions of the ABCD transporters are summarized along with the related disease.

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