Malonyl-CoA Abnormal Inhibition of Residual Enzyme Activity in Carnitine Palmitoyltransferase Deficiency

1986 ◽  
Vol 25 (4) ◽  
pp. 309-316 ◽  
Author(s):  
Carlo P. Trevisan ◽  
Corrado Angelini ◽  
Antonio Fiorellini ◽  
Grazia Isaya ◽  
Graziella Zacchello
Keyword(s):  
Enzyme Activity ◽  
Carnitine Palmitoyltransferase ◽  
Residual Enzyme Activity ◽  
Malonyl Coa ◽  
Carnitine Palmitoyltransferase Deficiency

Nε-Acetyl L-α Lysine Improves Activity and Stability of α-Amylase at Acidic Conditions: A Comparative Study with other Osmolytes

2020 ◽  
Vol 27 (6) ◽  
pp. 551-556
Author(s):  
Nidhya N. Joghee ◽  
Gurunathan Jayaraman ◽  
Masilamani Selladurai
Keyword(s):  
Enzyme Activity ◽  
Amino Acid ◽  
Thermodynamic Stability ◽  
Protective Effects ◽  
Residual Enzyme Activity ◽  
Functional Stability ◽  
Biotechnological Applications ◽  
Optimal Temperature ◽  
Acidic Conditions ◽  
Cellular Components

Background: Nε-acetyl L-α lysine is an unusual acetylated di-amino acid synthesized and accumulated by certain halophiles under osmotic stress. Osmolytes are generally known to protect proteins and other cellular components under various stress conditions. Objective: The structural and functional stability imparted by Nε-acetyl L-lysine on proteins were unknown and hence was studied and compared to other commonly known bacterial osmolytes - ectoine, proline, glycine betaine, trehalose and sucrose. Methods: Effects of osmolytes on the temperature and pH profiles, pH stability and thermodynamic stability of the model enzyme, α-amylase were analyzed. Results: At physiological pH, all the osmolytes under study increased the optimal temperature for enzyme activity and improved the thermodynamic stability of the enzyme. At acidic conditions (pH 3.0), Nε-acetyl L-α lysine and ectoine improved both the catalytic and thermodynamic stability of the enzyme; it was reflected in the increase in residual enzyme activity after incubation of the enzyme at pH 3.0 for 15 min by 60% and 63.5% and the midpoint temperature of unfolding transition by 11°C and 10°C respectively. Conclusion: Such significant protective effects on both activity and stability of α-amylase imparted by addition of Nε-acetyl L-α lysine and ectoine at acidic conditions make these osmolytes interesting candidates for biotechnological applications.

scholarly journals Effects of dl-2-bromopalmitoyl-CoA and bromoacetyl-CoA in rat liver and heart mitochondria. Inhibition of carnitine palmitoyltransferase and displacement of [14C]malonyl-CoA from mitochondrial binding sites

1985 ◽  
Vol 230 (1) ◽  
pp. 169-179 ◽  
Author(s):  
M R Edwards ◽  
M I Bird ◽  
E D Saggerson
Keyword(s):  
Binding Site ◽  
Rat Liver ◽  
Binding Sites ◽  
Liver Mitochondria ◽  
Carnitine Palmitoyltransferase ◽  
Heart Mitochondria ◽  
Nitrobenzoic Acid ◽  
Malonyl Coa ◽  
Tissue Differences ◽  
The Relationship

The overt form of carnitine palmitoyltransferase (CPT1) in rat liver and heart mitochondria was inhibited by DL-2-bromopalmitoyl-CoA and bromoacetyl-CoA. S-Methanesulphonyl-CoA inhibited liver CPT1. The inhibitory potency of DL-2-bromopalmitoyl-CoA was 17 times greater with liver than with heart CPT1. Inhibition of CPT1 by DL-2-bromopalmitoyl-CoA was unaffected by 5,5′-dithiobis-(2-nitrobenzoic acid) or (in liver) by starvation. In experiments in which DL-2-bromopalmitoyl-CoA displaced [14C]malonyl-CoA bound to liver mitochondria, the KD (competing) was 25 times the IC50 for inhibition of CPT1 providing evidence that the malonyl-CoA-binding site is unlikely to be the same as the acyl-CoA substrate site. Bromoacetyl-CoA inhibition of CPT1 was more potent in heart than in liver mitochondria and was diminished by 5,5′-dithiobis-(2-nitrobenzoic acid) or (in liver) by starvation. Bromoacetyl-CoA displaced bound [14C]malonyl-CoA from heart and liver mitochondria. In heart mitochondria this displacement was competitive with malonyl-CoA and was considerably facilitated by L-carnitine. In liver mitochondria this synergism between carnitine and bromoacetyl-CoA was not observed. It is suggested that bromoacetyl-CoA interacts with the malonyl-CoA-binding site of CPT1. L-Carnitine also facilitated the displacement by DL-2-bromopalmitoyl-CoA of [14C]malonyl-CoA from heart, but not from liver, mitochondria. DL-2-Bromopalmitoyl-CoA and bromoacetyl-CoA also inhibited overt carnitine octanoyl-transferase in liver and heart mitochondria. These findings are discussed in relation to inter-tissue differences in (a) the response of CPT1 activity to various inhibitors and (b) the relationship between high-affinity malonyl-CoA-binding sites and those sites for binding of L-carnitine and acyl-CoA substrates.

scholarly journals Hepatic mitochondrial inner-membrane properties, β-oxidation and carnitine palmitoyltransferases A and B. Effects of genetic obesity and starvation

1986 ◽  
Vol 233 (2) ◽  
pp. 427-433 ◽  
Author(s):  
L J Brady ◽  
C L Hoppel ◽  
P S Brady
Keyword(s):  
Membrane Fluidity ◽  
Carnitine Palmitoyltransferase ◽  
Membrane Properties ◽  
Zucker Rats ◽  
Beta Oxidation ◽  
Inner Membrane ◽  
Membrane Polarization ◽  
Mitochondrial Inner Membrane ◽  
Malonyl Coa ◽  
Obese Rats

Hepatic mitochondrial carnitine palmitoyltransferase (CPT) properties, beta-oxidation of palmitoyl-CoA and membrane polarization were measured in lean and obese Zucker rats. The Vmax. of the ‘outer’ carnitine palmitoyltransferase (‘CPT-A‘) increased with starvation, with no change in the Km for either carnitine or palmitoyl-CoA. The Ki for malonyl-CoA increased with starvation in lean rats, but not in obese rats. The Vmax. of the ‘inner’ enzyme (‘CPT-B‘), as measured by using inverted submitochondrial vesicles, increased with starvation in obese rats only, with no change in the Km for either carnitine or palmitoyl-CoA. The Ki for malonyl-CoA was 2-5-fold higher in inverted vesicles than in intact mitochondria, and showed no alteration with starvation. The activities of both enzymes correlated positively with each other and with beta-oxidation, and inversely with membrane polarization. Malonyl-CoA had little effect on gross membrane fluidity in the Zucker rat, as reflected by diphenylhexatriene fluorescence polarization. The results indicate that both enzymes are related and respond similarly to alterations in membrane fluidity. Membrane fluidity may provide a mechanism for co-ordinated control of CPT activity on both sides of the mitochondrial inner membrane.

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