Interpretation of the Kinetics of Consecutive Enzyme-catalysed Reactions: Studies on the Arginase-Ornithine Carbamoyltransferase System

Teasdale, RD; Pd, Jeffrey; Kuchel, PW; Nichol, LW

doi:10.1071/bi9820137

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…OCT can support increased flux without an increase in enzyme level, possibly because of the activation by Mn 2ϩ (68). Arginase also demonstrates linear first-order kinetics to increasing concentrations of plasma arginine (65). Thus the present studies confirm a large body of work demonstrating upregulation of urea cycle enzymes in diabetes.…”

Section: Ajp-endocrinol Metabsupporting

confidence: 78%

Proteomic changes associated with diabetes in the BB-DP rat

Johnson

Harris²,

French

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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These studies were structured with the aim of utilizing emerging technologies in two-dimensional (2D) gel electrophoresis and mass spectrometry to evaluate protein expression changes associated with type 1 diabetes. We reasoned that a broad examination of diabetic tissues at the protein level might open up novel avenues of investigation of the metabolic and signaling pathways that are adversely affected in type 1 diabetes. This study compared the protein expression of the liver, heart, and skeletal muscle of diabetes-prone rats and matched control rats by semiquantitative liquid chromatography-mass spectrometry and differential in-gel 2D gel electrophoresis. Differential expression of 341 proteins in liver, 43 in heart, and 9 (2D gel only) in skeletal muscle was detected. These data were assembled into the relevant metabolic pathways affected primarily in liver. Multiple covalent modifications were also apparent in 2D gel analysis. Several new hypotheses were generated by these data, including mechanisms of net cytosolic protein oxidation, formaldehyde generation by the methionine cycle, and inhibition of carbon substrate oxidation via reduction in citrate synthase and short-chain acyl-CoA dehydrogenase. metabolism; acyl carnitine; citrate synthase; methionine; liver; heart; skeletal muscle; mass spectroscopy; two-dimensional gel electrophoresis ALTHOUGH EXTENSIVELY STUDIED, type 1 diabetes remains a major health concern, and much of the pathogenesis still eludes understanding. In the Diabetes Control and Complications Trial, the most strongly regulated subjects still developed complications despite aggressive intervention (35). The fundamental pathology of type 1 diabetes is the loss of pancreatic ␤-cell function and the related release of insulin in the regulation of overall metabolic functions of the body. The complications of type 1 diabetes include dramatically altered energy metabolism and glucose handling, protein oxidation, vascular disease, heart disease, retinopathy, neuropathies, nephropathy, and susceptibility to infections. These results showed that the pathology of diabetes exceeds the simple maintenance of plasma glucose and insulin levels. A more global assessment of the diabetic state may provide useful insight. These studies sought to perform a comprehensive screen of the proteomic changes associated with the type 1 diabetic state, utilizing emerging technology in high-throughput semiquantitative proteomics and two-dimensional (2D) gel electrophoresis to detect protein expression differences as well as possible covalent modifications inherent to the diabetic state.Previous studies have revealed that many enzymes and proteins are under transitional control by insulin (45) that would predictably alter the content of these proteins with the reduction of insulin in type 1 diabetes. The major transcription factors involved in insulin action are adipocyte differentiation and determination factor (ADD)-1/sterol regulatory element binding protein (SREBP)-1/peroxisome proliferator-activated receptor (PP...

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Section: Ajp-endocrinol Metabsupporting

confidence: 78%

Proteomic changes associated with diabetes in the BB-DP rat

Johnson

Harris²,

French

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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“…Many of the enzymes in the urea cycle are upregulated in DM [30, 33]. Argininosuccinate synthetase(control/T1DM = 2.74, T1DM/AFB1 = 1.08), argininosuccinate synthase (control/T1DM = 1.73, T1DM/AFB1 = 0.86)) and arginase-1(control/T1DM = 1.68, T1DM/AFB1 = 0.96), participants in the urea cycle, were decreased in the T1DM group in our study.…”

Section: Discussionmentioning

confidence: 99%

The comparison of CHCA solvent compositions for improving LC-MALDI performance and its application to study the impact of aflatoxin B1 on the liver proteome of diabetes mellitus type 1 mice

et al. 2017

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In nanoflow liquid chromatography-matrix-assisted laser desorption/ionization tandem time-of-flight (nanoLC-MALDI-TOF/TOF) approaches, it is critical to directly apply small amounts of the sample elutes on the sample target using a nanoLC system due to its low flow rate of 200 ~ 300 nl/min. It is recommended to apply a sheath liquid containing a matrix with a several μL/min flow rate at the end of the nanoLC column to ensure a larger co-eluted droplet for more reproducible sample spotting and avoid the laborious task of post-manual matrix spotting. In this study, to achieve a better nanoLC-MALDI performance on sample spotting, we first compared α-Cyano-4-hydroxycinnamic acid (CHCA) solvent composition for efficiently concentrating nanoLC elutes on an anchor chip. The solvent composition of isopropanol (IPA): acetonitrile (ACN):acetone:0.1% Trifluoroacetic acid (TFA) (2:7:7:2) provided strong and homogeneous signals with higher peptide ion yields than the other solvent compositions. Then, nanoLC-MALDI-TOF/TOF was applied to study the impact of aflatoxin B1 on the liver proteome from diabetes mellitus type 1 mice. Aflatoxin B1 (AFB1), produced by Aspergillus flavus and Aspergillus parasiticus is a carcinogen and a known causative agent of liver cancer. To evaluate the effects of long-term exposure to AFB1 on type 1 diabetes mellitus (TIDM), the livers of T1DM control mice and mice treated with AFB1 were analyzed using isotope-coded protein labeling (ICPL)-based quantitative proteomics. Our results showed that gluconeogenesis, lipid, and oxidative phosphorylation mechanisms, normally elevated in T1DM, were disordered following AFB1 treatment. In addition, major urinary protein 1 (MUP1), an indicator of increased insulin sensitivity, was significantly decreased in the T1DM/AFB1 group and may have resulted in higher blood glucose levels compared to the T1DM group. These results indicate that T1DM patients should avoid the AFB1 intake, as they could lead to increased blood glucose levels and disorders of energy-producing mechanisms.

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The effect of feedback on pathway transient response

Easterby¹

1986

Biochemical Journal

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The effect of variation of the rate of input of material on the transient behaviour of metabolic pathways is examined. This reveals the existence of three transient times which make up the overall pathway transient. Two of these have been described previously and represent the times required for the accumulation of the free intermediate pool and the pool of enzyme-bound intermediate. They are state functions and as such are independent of the way in which the steady state was reached. The third is attributable to the variation in the rate of input of material to the pathway. It is dependent on three further factors. These are (a) the time required for the initial enzyme to reach its own steady state, (b) substrate depletion and (c) feedback. The description of the transient is: (Formula: see text) where V0 represents the rate of input and Vss represents the steady-state flux. The transient time associated with the transition between steady-states is shown to be a simple function of the transients for the establishment of each steady state from rest and may be expressed as: tau = tau b-Va/Vb . tau a where Va and Vb refer to the fluxes in the two steady states and tau a and tau b represent the transient times for the establishment of each of the steady-states from rest. The total pathway transient may now be completely defined as: (formula: see text) where summation over all intermediates, I, is implied. The significance of this to the analysis of pathway behaviour is discussed with more general examples of pathway transient analysis.

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Interpretation of the Kinetics of Consecutive Enzyme-catalysed Reactions: Studies on the Arginase-Ornithine Carbamoyltransferase System

Cited by 3 publications

References 10 publications

Proteomic changes associated with diabetes in the BB-DP rat

Proteomic changes associated with diabetes in the BB-DP rat

The comparison of CHCA solvent compositions for improving LC-MALDI performance and its application to study the impact of aflatoxin B1 on the liver proteome of diabetes mellitus type 1 mice

The effect of feedback on pathway transient response

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