scholarly journals Effects of administration of tri-iodothyronine on the response of cardiac and renal pyruvate dehydrogenase complex to starvation for 48 h

1985 ◽  
Vol 232 (1) ◽  
pp. 255-259 ◽  
Author(s):  
M J Holness ◽  
T N Palmer ◽  
M C Sugden
Keyword(s):  
Fatty Acids ◽  
Steady State ◽  
Fatty Acid ◽  
Pyruvate Dehydrogenase ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Pyruvate Dehydrogenase Complex ◽  
Active Form ◽  
Complex Activities ◽  
Dehydrogenase Complex

Effects of administration of tri-iodothyronine (T3) on activities of cardiac and renal pyruvate dehydrogenase complex (active form, PDHa) were investigated. In fed rats, T3 treatment did not affect cardiac or renal PDHa activity, although blood non-esterified fatty acid and ketone-body concentrations were increased. Starvation (48 h) of both control and T3-treated rats resulted in similar increases in the steady-state concentrations of fatty acids and ketone bodies, but inactivation of cardiac and renal pyruvate dehydrogenase complex activities was diminished by T3 treatment. Inhibition of lipolysis increased renal and cardiac PDHa in control but not in T3-treated 48 h-starved rats, despite decreased fatty acid and ketone-body concentrations in both groups. The results suggest that hyperthyroidism influences the response of cardiac and renal PDHa activities to starvation through changes in the metabolism of lipid fuels in these tissues.

Loss of fatty acid control of gluconeogenesis and PDH complex flux in adrenalectomized rats

1994 ◽  
Vol 267 (4) ◽  
pp. E528-E536 ◽  
Author(s):  
G. Cipres ◽  
E. Urcelay ◽  
N. Butta ◽  
M. S. Ayuso ◽  
R. Parrilla ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Reducing Power ◽  
Acid Control ◽  
Body Production ◽  
Rat Livers ◽  
Complex Flux ◽  
Dehydrogenase Complex

This work aimed to determine the role played by the adrenal gland in the fatty acid control of gluconeogenesis in isolated perfused rat livers. The gluconeogenic substrate concentration responses were not altered in adrenalectomized (ADX) rats. This observation indicates that glucocorticoids are not essential to maintain normal basal gluconeogenic rates. In contrast, fatty acid failed to stimulate gluconeogenesis from lactate and elicited attenuated stimulation with pyruvate as substrate in livers from ADX rats. Fatty acid-induced stimulation of respiration and ketone body production were similar in control and ADX rats. Thus the diminished responsiveness of the gluconeogenic pathway to fatty acid cannot be the result of different rates of energy production and/or generation of reducing power. Fatty acids did not inhibit pyruvate decarboxylation in livers from ADX rats. Even though mitochondria isolated from livers of ADX rats showed normal basal rates of pyruvate metabolism, fatty acids failed to inhibit pyruvate decarboxylation and the activity of the pyruvate dehydrogenase complex. This novel observation of the glucocorticoid effect in controlling the pyruvate dehydrogenase complex responsiveness indicates that the mitochondrial partitioning of pyruvate between carboxylation and decarboxylation reactions may be altered in livers from ADX rats. We propose that the diminished effect of fatty acid in stimulating gluconeogenesis in livers from ADX rats is the result of a limited pyruvate availability for the carboxylase reaction due to a lack of inhibition of flux through the pyruvate dehydrogenase complex.

On the Specificity of the Herbicide Chlorsulfuron in Intact Spinach Chloroplasts

1985 ◽  
Vol 40 (11-12) ◽  
pp. 917-918 ◽  
Author(s):  
Uwe Homeyer ◽  
D. Schulze-Siebert ◽  
G. Schultz
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Acid Synthesis ◽  
Spinach Chloroplasts ◽  
Transamination Reaction ◽  
Dehydrogenase Complex

Abstract In vitro incubation of intact spinach chloroplasts with 1 mᴍ Pyruvate was used to study the specificity of action of the herbicide Chlorsulfuron on the synthesis of valine, alanine and fatty acids. As a result, increasing concentrations of the herbicide strongly inhibited valine synthesis while fatty acid synthesis via pyruvate dehydrogenase complex (PDC) and alanine formation by transamination reaction was promoted.

scholarly journals Lack of mitochondria-generated acetyl-CoA by pyruvate dehydrogenase complex downregulates gene expression in the hepatic de novo lipogenic pathway

2016 ◽  
Vol 311 (1) ◽  
pp. E117-E127 ◽  
Author(s):  
Saleh Mahmood ◽  
Barbara Birkaya ◽  
Todd C. Rideout ◽  
Mulchand S. Patel
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Pyruvate Dehydrogenase ◽  
De Novo ◽  
Pyruvate Dehydrogenase Complex ◽  
Acid Oxidation ◽  
Acetyl Coa ◽  
Key Genes ◽  
Dehydrogenase Complex

During the absorptive state, the liver stores excess glucose as glycogen and synthesizes fatty acids for triglyceride synthesis for export as very low density lipoproteins. For de novo synthesis of fatty acids from glucose, the mitochondrial pyruvate dehydrogenase complex (PDC) is the gatekeeper for the generation of acetyl-CoA from glucose-derived pyruvate. Here, we tested the hypothesis that limiting the supply of PDC-generated acetyl-CoA from glucose would have an impact on expression of key genes in the lipogenic pathway. In the present study, although the postnatal growth of liver-specific PDC-deficient (L-PDCKO) male mice was largely unaltered, the mice developed hyperinsulinemia with lower blood glucose levels in the fed state. Serum and liver lipid triglyceride and cholesterol levels remained unaltered in L-PDCKO mice. Expression of several key genes ( ACL, ACC1) in the lipogenic pathway and their upstream regulators ( LXR, SREBP1, ChREBP) as well as several genes in glucose metabolism ( Pklr, G6pd2, Pck1) and fatty acid oxidation ( FAT, Cpt1a) was downregulated in livers from L-PDCKO mice. Interestingly, there was concomitant upregulation of lipogenic genes in adipose tissue from L-PDCKO mice. Although, the total hepatic acetyl-CoA content remained unaltered in L-PDCKO mice, modified acetylation profiles of proteins in the nuclear compartment suggested an important role for PDC-generated acetyl-CoA in gene expression in de novo fatty acid synthesis in the liver. This finding has important implications for the regulation of hepatic lipid synthesis in pathological states.

scholarly journals The relationship between changes in lipid fuel availability and tissue fructose 2,6-bisphosphate concentrations and pyruvate dehydrogenase complex activities in the fed state

1988 ◽  
Vol 256 (3) ◽  
pp. 935-939 ◽  
Author(s):  
T J French ◽  
A W Goode ◽  
M J Holness ◽  
P A MacLennan ◽  
M C Sugden
Keyword(s):  
Fatty Acids ◽  
Pyruvate Dehydrogenase ◽  
Surgical Stress ◽  
Pyruvate Dehydrogenase Complex ◽  
Elevated Concentration ◽  
Fed State ◽  
Esterified Fatty Acids ◽  
The Relationship ◽  
Complex Activities ◽  
Dehydrogenase Complex

An elevated concentration of non-esterified fatty acids in the fed state elicited inhibition of cardiac, but not hepatic, pyruvate dehydrogenase complex (PDH). There was a modest decline in fructose 2,6-bisphosphate (Fru-2,6-P2) concentration in heart, and, to a lesser extent, in liver. Surgical stress decreased PDH activities and Fru-2,6-P2 concentrations in both heart and liver. Only the former response was abolished if postoperative lipolysis was inhibited. Surgery also decreased the [Fru-2,6-P2] in gastrocnemius: this response was abolished if lipolysis was inhibited.

Inhibition of the Plastidic Pyruvate Dehydrogenase Complex in Isolated Plastids of Oat

1994 ◽  
Vol 49 (7-8) ◽  
pp. 421-426 ◽  
Author(s):  
Andrea Golz ◽  
Hartmut K. Lichtenthaler
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Pyruvate Dehydrogenase ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Pyruvate Dehydrogenase Complex ◽  
Dependent Manner ◽  
Acid Biosynthesis ◽  
Acetyl Coa ◽  
Dehydrogenase Complex

The activity of the plastidic pyruvate dehydrogenase complex (pPDHC) is one source of acetyl-CoA in plastids of higher plants needed for de novo fatty acid biosynthesis. This plastidic enzyme reaction is specifically inhibited by acetylmethylphosphinate (AMPI), a com ­ pound which had hitherto been known only as an inhibitor of the mitochondrial pyruvate dehydrogenase complex (mPDHC). In the test system of isolated intact oat plastids (Avena sativa) [2-14C]pyruvate was used for de novo fatty acid biosynthesis. The incorporation of label from [2-14C]pyruvate in fatty acids was inhibited by AMPI in a dose-dependent manner. The inhibition rose with increasing preincubation time of plastids with the inhibitor. I50 values for the inhibition of de novo fatty acid biosynthesis from [2-14C]pyruvate by AMPI for iso­lated etioplasts and chloroplasts were 4.5 and 80 μm , respectively. The activity of the pPDHC decreased during greening of oat seedlings, as is seen from the decreasing incorporation of [2-14C]pyruvate into fatty acids during the light-induced transformation of etioplasts into chloroplasts. In contrast to the decreasing pPDHC activity, the activity of the plastidic acetyl-C oA synthetase (ACS), which transfers acetate to acetyl-CoA, rose parallel to the transfor­mation of etioplasts into chloroplasts. During the assay time of 20 min we could not detect an incorporation of radiolabel from pyruvate or acetate into β-carotene or any other carotenoid

Enzyme activities of D-glucose metabolism in the fission yeast Schizosaccharomyces pombe

1992 ◽  
Vol 38 (12) ◽  
pp. 1313-1319 ◽  
Author(s):  
C. S. Tsai ◽  
J.-L. Shi ◽  
B. W. Beehler ◽  
B. Beck
Keyword(s):  
Steady State ◽  
Alcohol Dehydrogenase ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Pyruvate Decarboxylase ◽  
Washout Rate ◽  
Synthetase Activity ◽  
Dehydrogenase Complex

The activities of key enzymes that are members of D-glucose metabolic pathways in Schizosaccharomyces pombe undergoing respirative, respirofermentative, and fermentative metabolisms are monitored. The steady-state activities of glycolytic enzymes, except phosphofructokinase, decrease with a reduced efficiency in D-glucose utilization by yeast continuous culture. On the other hand, the enzymic activities of pentose monophosphate pathway reach the maximum when the cell mass production of the cultures is optimum. Enzymes of tricarboxylate cycle exhibit the maximum activities at approximately the washout rate. The steady-state activity of pyruvate dehydrogenase complex increases rapidly when D-glucose is efficiently utilized. By comparison, the activity of pyruvate decarboxylase begins to increase only when ethanol production occurs. Depletion of dissolved oxygen suppresses the activity of pyruvate dehydrogenase complex but facilitates that of pyruvate decarboxylase. Acetate greatly enhances the acetyl CoA synthetase activity. Similarly, ethanol stimulates alcohol dehydrogenase and aldehyde dehydrogenase activities. Evidence for the existence of alcohol dehydrogenase isozymes in the fission yeast is presented. Key words: yeast, glucose-metabolizing enzymes.

scholarly journals Expressing a cytosolic pyruvate dehydrogenase complex to increase free fatty acid production in Saccharomyces cerevisiae

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Yiming Zhang ◽  
Mo Su ◽  
Ning Qin ◽  
Jens Nielsen ◽  
Zihe Liu
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Pyruvate Dehydrogenase ◽  
Unsaturated Fatty Acids ◽  
Pyruvate Dehydrogenase Complex ◽  
Cell Factory ◽  
Acetyl Coa ◽  
Fatty Acid Production

Abstract Background Saccharomyces cerevisiae is being exploited as a cell factory to produce fatty acids and their derivatives as biofuels. Previous studies found that both precursor supply and fatty acid metabolism deregulation are essential for enhanced fatty acid synthesis. A bacterial pyruvate dehydrogenase (PDH) complex expressed in the yeast cytosol was reported to enable production of cytosolic acetyl-CoA with lower energy cost and no toxic intermediate. Results Overexpression of the PDH complex significantly increased cell growth, ethanol consumption and reduced glycerol accumulation. Furthermore, to optimize the redox imbalance in production of fatty acids from glucose, two endogenous NAD+-dependent glycerol-3-phosphate dehydrogenases were deleted, and a heterologous NADP+-dependent glyceraldehyde-3-phosphate dehydrogenase was introduced. The best fatty acid producing strain PDH7 with engineering of precursor and co-factor metabolism could produce 840.5 mg/L free fatty acids (FFAs) in shake flask, which was 83.2% higher than the control strain YJZ08. Profile analysis of free fatty acid suggested the cytosolic PDH complex mainly resulted in the increases of unsaturated fatty acids (C16:1 and C18:1). Conclusions We demonstrated that cytosolic PDH pathway enabled more efficient acetyl-CoA provision with the lower ATP cost, and improved FFA production. Together with engineering of the redox factor rebalance, the cytosolic PDH pathway could achieve high level of FFA production at similar levels of other best acetyl-CoA producing pathways.

scholarly journals Relationship between plasma and muscle concentrations of ketone bodies and free fatty acids in fed, starved and alloxan-diabetic states

1973 ◽  
Vol 134 (2) ◽  
pp. 499-506 ◽  
Author(s):  
Oliver E. Owen ◽  
Helene Markus ◽  
Stuart Sarshik ◽  
Maria Mozzoli
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Free Fatty Acids ◽  
Plasma Glucose ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Water Concentration ◽  
Diabetic Rats ◽  
Muscle Membrane

1. Concentrations of ketone bodies, free fatty acids and chloride in fed, 24–120h-starved and alloxan-diabetic rats were determined in plasma and striated muscle. Plasma glucose concentrations were also measured in these groups of animals. 2. Intracellular metabolite concentrations were calculated by using chloride as an endogenous marker of extracellular space. 3. The mean intracellular ketone-body concentrations (±s.e.m.) were 0.17±0.02, 0.76±0.11 and 2.82±0.50μmol/ml of water in fed, 48h-starved and alloxan-diabetic rats, respectively. Mean (intracellular water concentration)/(plasma water concentration) ratios were 0.47, 0.30 and 0.32 in fed, 48h-starved and alloxan-diabetic rats respectively. The relationship between ketone-body concentrations in the plasma and intracellular compartments appeared to follow an asymptotic pattern. 4. Only intracellular 3-hydroxybutyrate concentrations rose during starvation whereas concentrations of both 3-hydroxybutyrate and acetoacetate were elevated in the alloxan-diabetic state. 5. During starvation plasma glucose concentrations were lowest at 48h, and increased with further starvation. 6. There was no significant difference in the muscle intracellular free fatty acid concentrations of fed, starved and alloxan-diabetic rats. Mean free fatty acid intramuscular concentrations (±s.e.m.) were 0.81±0.08, 0.98±0.21 and 0.91±0.10μmol/ml in fed, 48h-starved and alloxan-diabetic states. 7. The intracellular ketosis of starvation and the stability of free fatty acid intracellular concentrations suggests that neither muscle membrane permeability nor concentrations of free fatty acids per se are major factors in limiting ketone-body oxidation in these states.

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