Calcineurin is a eukaryotic Ca2+- and calmodulin-dependent serine/threonine protein phosphatase. It is a heterodimeric protein consisting of a catalytic subunit calcineurin A, which contains an act...

https://www.physiology.org/doi/pdf/10.1152/physrev.2000.80.4.1483

Calcineurin : form and function

Regulation of the Calmodulin-stimulated Protein Phosphatase, Calcineurin

The final unique stage in the metabolism of L-isoleucine involves the cleavage of 2-methylacetoacetyl-CoA to acetyl-CoA and propionyl-CoA (Section 104) The propionyl-CoA is further metabolized to methylmalonyl-CoA by a biotin-dependent carboxylase and subsequently via succinyl-CoA into the tricarboxylic acid cycle L-Valine is also metabolized ultimately to methylmalonyl-CoA (Section 104), and thus these two branched-chain amino acids form the major precursors of propionyl-CoA and methylmalonyl-CoA Other precursors of propionyl-CoA include methionine, threonine, oddcarbon-number fatty acids and cholesterol The methylmalonyl-CoA produced by propionyl-CoA carboxylase occurs as the D(S)-enantiomer and is racemized to the L(R)-enantiomer by methylmalonyl-CoA racemase L(R)Methylmalonyl-CoA is then metabolized to succinyl-CoA by a vitamin B12-dependent mutase prior to introduction of the modified molecule into the tricarboxylic acid cycle

Disorders of propionate and methylmalonate metabolism

'Wash-out' and inactivation of the Ca current were examined in dialysed, voltage-clamped neurones of Helix aspersa under conditions that isolate the Ca current virtually free of other currents. EGTA or other internal Ca2+ chelators were routinely omitted from the dialysate. The time-dependent loss, or wash-out, of Ca current was slowed by addition to the dialysing solution of agents, such as dibutyryl adenosine 3'-5'-cyclic monophosphate (dibutyryl cyclic AMP), Mg adenosine 5'-triphosphate (ATP) and the catalytic subunit of cyclic-AMP-dependent protein kinase, that promote protein phosphorylation and by EGTA. However, neither the phosphorylation-promoting agents nor internal EGTA prevented wash-out entirely, nor did they significantly restore previously 'washed-out' current. With phosphorylating agents in the dialysing solution, the irreversible development of wash-out was greatly reduced by introduction of leupeptin, an inhibitor of protease activity. Thus, the irreversible component of wash-out appears to result from a Ca-dependent proteolytic process. In the presence of leupeptin alone, Ca current amplitude continued to decline: however, the current could be largely or fully restored with addition of catalytic subunit, dibutyryl cyclic AMP, and Mg ATP to the dialysing solution. Thus, inhibition of proteolysis revealed a reversible component of wash-out that appears to result from dephosphorylation. During perfusion with leupeptin, Mg ATP, dibutyryl cyclic AMP and catalytic subunit the Ca current remained stable for up to several hours without addition of internal Ca2+ buffer. The rate of inactivation of the current that occurs during a depolarizing step showed only a very gradual decline during this time. Under these conditions, perfusion with calcineurin, a Ca-calmodulin-dependent phosphatase, caused a significant increase in the rate of Ca current inactivation. This inactivation was virtually eliminated by introduction of EGTA or by replacement of external Ca2+ with Ba2+, which is consistent with the ion dependency for calmodulin-dependent activation of calcineurin. When ATP in the dialysate was replaced with ATP-gamma-S (adenosine 5'-O-(thiotriphosphate], an analogue that donates a thiophosphate group resistant to hydrolysis, the rate of inactivation slowed. Since Ca-dependent inactivation during step depolarizations is enhanced by conditions that promote dephosphorylation, and Ca current wash-out is slowed by conditions that promote phosphorylation, inactivation and reversible wash-out appear to be related.(ABSTRACT TRUNCATED AT 400 WORDS)

/pdf/an-enzymatic-mechanism-for-calcium-current-inactivation-in-1ntdp898df.pdf

An enzymatic mechanism for calcium current inactivation in dialysed Helix neurones.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2888%2980628-8

Two adjacent cysteine residues in the C-terminal cytoplasmic fragment of bovine rhodopsin are palmitylated

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2882%2980759-X

Identification of the NH2‐terminal blocking group of calcineurin B as myristic acid

Stable isotope ratio analysis of leucine and ketoisocaproic acid in blood plasma by gas chromatography/mass spectrometry. Use of tertiary butyldimethylsilyl derivatives

A concentrate of branched chain fatty acids (as methyl esters) was prepared from the triacylglycerols of subcutaneous adipose tissue lipids of lambs receiving a carbohydrate-rich (cereal) diet. This was accomplished by procedures which allowed the removal of unsaturated components by peroxidation and straight chain saturated components by urea-adduct formation. The concentrate was analyzed by high resolution gas chromatography in combination with mass spectrometry and was shown to consist of a complex mixture of saturated methyl-substituted fatty acids. Methyl substitution occurred on even-numbered carbon atoms (relative to the carboxyl group) and the chain lengths of the acids ranged from 10 to 18 carbon atoms. Acids with one methyl substituent in the fatty acyl chain were most abundant; di-, tri- and tetramethyl-substituted acids were also present. The biosynthesis of these methyl-substituted acids is discussed briefly.

Identification of methyl-branched fatty acids from the triacylglycerols of subcutaneous adipose tissue of lambs.

Mid-chain ethyl substituted fatty acids with chain lengths ranging from 10 to 16 carbon atoms were identified in a concentrate of branched chain fatty acids isolated from the triacylglycerol fatty acids of the subcutaneous adipose tissue of barley-fed lambs. The acids were identified by gas chromatography in combination with mass spectrometry and their mass spectral features are discussed.

Characterization of ethyl substituted fatty acids from lamb subcutaneous triacylglycerols by combined gas chromatography mass spectrometry.

Branched-chain fatty acids (BCFA) were prepared as a concentrate from the adiposetissue lipids of barley-fed lambs. The BCFA was included in a stock Oxoid ration at levels of 2.5–15% by weight and these diets were given to appetite to female weanling rats for up to 14 days. The influence of the diets on inter alia growth-rate and fatty acid composition of tissue lipids was compared with the effect of the same stock diet with inclusions at a level of 5% by weight of 3-methylhexadecanoic acid (3-MHD), 4-methylhexadecanoic acid (4-MHD), 3,7,11,15-tetramethylhexadecanoic (phytanic) acid and n-hexadecanoic (palmitic) acid which, with the stock ration, served as control. Rats receiving diets containing up to 7.5% BCFA grew almost as well as did those given palmitic acid whereas the animals offered the diets containing 3-MHD, 4-MHD or 10% BCFA barely subsisted. Rats given 10% BCFA or phytanic acid became moribund within 3 days. BCFA accumulated to widely varying degrees in the lipids of the main internal organs. The higher proportions of these acids constituted some 40–60% of the total fatty acids of the lipids of kidney, liver and heart and were associated with diets containing 10% and 15% BCFA and 5% 3-MHD. The lower proportions of the branched acids in the lipids of these organs were in the range 15–25% of the total fatty acids and related to diets that included 2.5% BCFA and 5% 4-MHD. In contrast to the changes in fatty acid composition of the lipids of the main internal organs, those of the central and peripheral nervous systems were only minor, the proportions of branched acids amounting to some 3% in brain tissue and up to 14% in sciatic nerve. Clearance of branched acids from tissue lipids of the main internal organs was almost complete after the animals were returned to the basal diet for 14 days but the loss of branched acids from nerve tissue was evidently less rapid.

A Smith

Papers

Identification of the NH2‐terminal blocking group of calcineurin B as myristic acid

Stable isotope ratio analysis of leucine and ketoisocaproic acid in blood plasma by gas chromatography/mass spectrometry. Use of tertiary butyldimethylsilyl derivatives

Identification of methyl-branched fatty acids from the triacylglycerols of subcutaneous adipose tissue of lambs.

Characterization of ethyl substituted fatty acids from lamb subcutaneous triacylglycerols by combined gas chromatography mass spectrometry.

The influence of dietary branched‐chain fatty acids on the fatty acid composition of tissue lipids of rats