Tubulin tyrosine ligase: a shared fold with the glutathione synthetase ADP-forming family

Abstract The clinical and laboratory features of a 3-mo-old black male infant with glutathione (GSH) synthetase deficiency of the generalized type was evaluated. Partial albinism, brisk hemolytic anemia, recurrent febrile episodes, and mental retardation were noted. Also, severe recurrent metabolic acidosis and marked oxoprolinemia and oxoprolinuria were found in the proband but not in his first-degree relatives. The relationship of these disease manifestations to the underlying metabolic defect is discussed.

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Tubulin-tyrosine ligase catalyzes covalent binding of 3-fluoro-tyrosine to tubulin: kinetic and [19 F]NMR studies

FEBS Letters ◽

10.1016/0014-5793(95)01099-z ◽

1995 ◽

Vol 374 (2) ◽

pp. 165-168 ◽

Cited By ~ 10

Author(s):

Octavio Monasterio ◽

Esteban Nova ◽

Adamari López-Brauet ◽

Rosalba Lagos

Keyword(s):

Covalent Binding ◽

Nmr Studies ◽

Tubulin Tyrosine Ligase ◽

19 F Nmr

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Suppression of tubulin tyrosine ligase during tumor growth

Journal of Cell Science ◽

10.1242/jcs.111.2.171 ◽

1998 ◽

Vol 111 (2) ◽

pp. 171-181 ◽

Cited By ~ 5

Author(s):

L. Lafanechere ◽

C. Courtay-Cahen ◽

T. Kawakami ◽

M. Jacrot ◽

M. Rudiger ◽

...

Keyword(s):

Tumor Growth ◽

Selection Process ◽

Eukaryotic Cells ◽

C Terminus ◽

Tubulin Isotype ◽

Clonal Cell Lines ◽

Tubulin Tyrosine Ligase ◽

Nih 3T3 ◽

Tubulin Carboxypeptidase

The C terminus of the tubulin alpha-subunit of most eukaryotic cells undergoes a cycle of tyrosination and detyrosination using two specific enzymes, a tubulin tyrosine ligase (TTL) and a tubulin carboxypeptidase. Although this enzyme cycle is conserved in evolution and exhibits rapid turnover, the meaning of this modification has remained elusive. We have isolated several NIH-3T3 derived clonal cell lines that lack TTL (TTL-). TTL- cells contain a unique tubulin isotype (delta2-tubulin) that can be detected with specific antibodies. When injected into nude mice, both TTL- cells and TTL- cells stably transfected with TTL cDNA form sarcomas. But in tumors formed from TTL rescued cells, TTL is systematically lost during tumor growth. A strong selection process has thus acted during tumor growth to suppress TTL activity. In accord with this result, we find suppression of TTL activity in the majority of human tumors assayed with delta2-tubulin antibody. We conclude there is a widespread loss of TTL activity during tumor growth in situ, suggesting that TTL activity may play a role in tumor cell regulation.

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Alcoholic Stem Extract ofCoscinium fenestratumRegulates Carbohydrate Metabolism and Improves Antioxidant Status in Streptozotocin–Nicotinamide Induced Diabetic Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/neh099 ◽

2005 ◽

Vol 2 (3) ◽

pp. 375-381 ◽

Cited By ~ 54

Author(s):

I. R. Punitha ◽

K. Rajendran ◽

Arun Shirwaikar ◽

Annie Shirwaikar

Keyword(s):

Carbohydrate Metabolism ◽

Antioxidant Status ◽

Diabetic Rats ◽

Antidiabetic Activity ◽

Glutathione Synthetase ◽

Alcoholic Extract ◽

Enzymatic Antioxidants ◽

Stem Extract ◽

Gluconeogenic Enzyme ◽

Glucose 6 Phosphate Dehydrogenase

Alcoholic extract of the stems ofCoscinium fenestratum, a medicinal plant indigenous to India and Sri Lanka used in ayurveda and siddha medicine for treating diabetes, was studied for its carbohydrate metabolism effect and antioxidant status in streptozotocin–nicotinamide induced type 2 diabetic rats. Oral administration ofC. fenestratumstem extract in graded doses caused a significant increase in enzymatic antioxidants such as catalase, superoxide dismutase, glutathione synthetase, peroxidase, and glutathione peroxidase and in the nonenzymatic antioxidants ascorbic acid, ceruloplasmin and tocopherol. Effects of alcoholic extract on glycolytic enzymes such as glucose-6-phosphate dehydrogenase, lactate dehydrogenase and hexokinase showed a significant increase in their levels, whereas a significant decrease was observed in the levels of gluconeogenic enzyme, glucose-6-phosphatase and alanine aminotransferase in treated diabetic rats. Serum creatinine and urea levels also declined significantly. This investigation demonstrates significant antidiabetic activity ofC. fenestratum.

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Enhancement of Glutathione Content in Glutathione Synthetase-Deficient Fibroblasts from a Patient with 5-Oxoprolinuria via Metabolic Cooperation with Normal Fibroblasts

Experimental Cell Research ◽

10.1006/excr.1994.1119 ◽

1994 ◽

Vol 212 (1) ◽

pp. 69-76 ◽

Cited By ~ 6

Author(s):

Terrance J. Kavanagh ◽

Ganesh Raghu ◽

Collin C. White ◽

George M. Martin ◽

Peter S. Rabinovitch ◽

...

Keyword(s):

Glutathione Synthetase ◽

Metabolic Cooperation

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Intestinal Barrier Function and Performance of Broiler Chickens Fed Additional Arginine, Combination of Arginine and Glutamine or an Amino Acid-Based Solution

Animals ◽

10.3390/ani11082416 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2416

Author(s):

Reza Barekatain ◽

Tristan Chalvon-Demersay ◽

Clive McLaughlan ◽

William Lambert

Keyword(s):

Amino Acid ◽

Intestinal Permeability ◽

Broiler Chickens ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Basal Diet ◽

Intestinal Barrier Function ◽

Glutathione Synthetase ◽

Feed Conversion ◽

Experimental Treatments

Two experiments were conducted to investigate the effect of arginine (Arg); the combination of Arg and glutamine (Gln); as well as an amino acid-based solution (MIX) containing Arg, Gln, threonine (Thr), and grape extract, on performance, intestinal permeability, and expression of selected mechanistic genes. Using 240 male Ross 308 off-sex broiler chickens, four experimental treatments were replicated six times with 10 birds per replicate. The experimental treatments included 5 g/kg Arg, 2.5 g/kg Arg and 2.5 g/kg Gln, and 1 g/kg MIX added to a basal diet as control. In the second study, the four dietary treatments were then given to 24 birds with or without a synthetic glucocorticoid, dexamethasone (DEX), as a gut dysfunction model. Feed conversion ratio was improved by all the supplemented treatments from day 7 to 35 of age (p < 0.001). DEX injections increased (p < 0.001) the intestinal permeability in all treatments, which tended to be reversed by Arg or MIX. Additional Arg, Arg-Gln, and MIX suppressed (p < 0.05) the overexpression of IL-1β generated by DEX. Feeding birds with MIX treatment increased (p < 0.05) expression of SGLT-1 and glutathione synthetase. In conclusion, tested amino acid supplements were effective in improving feed efficiency and restraining intestinal inflammation caused by DEX through IL-1β pathway.

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Surface Display of a Bifunctional Glutathione Synthetase on Saccharomyces cerevisiae for Converting Chicken Feather Hydrolysate into Glutathione

Molecular Biotechnology ◽

10.1007/s12033-014-9750-4 ◽

2014 ◽

Vol 56 (8) ◽

pp. 726-730 ◽

Cited By ~ 6

Author(s):

Zhiqi Qiu ◽

Hongming Tan ◽

Shining Zhou ◽

Lixiang Cao

Keyword(s):

Saccharomyces Cerevisiae ◽

Surface Display ◽

Glutathione Synthetase ◽

Chicken Feather ◽

Bifunctional Glutathione Synthetase

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Glutathione replenishment capacity is lower in isolated perivenous than in periportal hepatocytes

Biochemical Journal ◽

10.1042/bj2540411 ◽

1988 ◽

Vol 254 (2) ◽

pp. 411-417 ◽

Cited By ~ 42

Author(s):

Y Kera ◽

K E Penttilä ◽

K O Lindros

Keyword(s):

Glutathione Synthetase ◽

Synthetase Activity ◽

Gamma Glutamyl Transpeptidase ◽

Zonal Distribution ◽

Significant Difference ◽

Glutamylcysteine Synthetase ◽

Gsh Metabolism ◽

Collagenase Perfusion ◽

Sulphur Amino Acids ◽

Glutamyl Transpeptidase

The zonal distribution of GSH metabolism was investigated by comparing hepatocytes obtained from the periportal (zone 1) or perivenous (zone 3) region by digitonin/collagenase perfusion. Freshly isolated periportal and perivenous cells had similar viability (dye exclusion, lactate dehydrogenase leakage and ATP content) and GSH content (2.4 and 2.7 mumol/g respectively). During incubation, periportal cells slowly accumulated GSH (0.35 mumol/h per g), whereas in perivenous cells a decrease occurred (-0.14 mumol/h per g). Also, in the presence of either L-methionine or L-cysteine (0.5 mM) periportal hepatocytes accumulated GSH much faster (3.5 mumol/h per g) than did perivenous cells (1.9 mumol/h per g). These periportal-perivenous differences were also found in cells from fasted rats. Efflux of GSH was faster from perivenous cells than from periportal cells, but this difference only explained 10-20% of the periportal-perivenous difference in accumulation. Furthermore, periportal cells accumulated GSH to a plateau 26-40% higher than in perivenous cells. There was no significant difference in gamma-glutamylcysteine synthetase or glutathione synthetase activity between the periportal and perivenous cell preparations. The periportal-perivenous difference in GSH accumulation was unaffected by inhibition of gamma-glutamyl transpeptidase or by 5 mM-glutamate or -glutamine, but was slightly diminished by 2 mM-L-methionine. This suggests differences between periportal and perivenous cells in their metabolism and/or transport of (sulphur) amino acids. Our results suggest that a lower GSH replenishment capacity of the hepatocytes from the perivenous region may contribute to the greater vulnerability of this region to xenobiotic damage.

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