282-OR: The Effect of Glucagon on Rates of Hepatic Mitochondrial Oxidation and Pyruvate Carboxylase Flux in Man Assessed by Positional Isotopomer NMR Tracer Analysis (PINTA)

Numerous studies have dealt with the cytochemical localization of cytochrome oxidase via cytochrome c. More recent studies have dealt with indicating initial foci of this reaction by altering incubation pH (1) or postosmication procedure (2,3). The following study is an attempt to locate such foci by altering membrane permeability. It is thought that such alterations within the limits of maintaining morphological integrity of the membranes will ease the entry of exogenous substrates resulting in a much quicker oxidation and subsequently a more precise definition of the oxidative reaction.The diaminobenzidine (DAB) method of Seligman et al. (4) was used. Minced pieces of rat liver were incubated for 1 hr following toluene treatment (5,6). Experimental variations consisted of incubating fixed or unfixed tissues treated with toluene and unfixed tissues treated with toluene and subsequently fixed.

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Mitochondrial Oxidation of p-N, N-Dimethylamino-β-Phenethylamine (DAPA)

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100115912 ◽

1975 ◽

Vol 33 ◽

pp. 458-459

Author(s):

W. Allen Shannon ◽

Hannah L. Wasserkrug ◽

andArnold M. Seligman

Keyword(s):

Guinea Pig ◽

Oxidase Activity ◽

Amine Oxidase ◽

Histochemical Demonstration ◽

Guinea Pig Heart ◽

Pig Kidney ◽

Cytoplasmic Vacuoles ◽

Liver And Kidney ◽

Mitochondrial Oxidation ◽

Amine Oxidase Activity

The synthesis of a new substrate, p-N,N-dimethylamino-β-phenethylamine (DAPA)3 (Fig. 1) (1,2), and the testing of it as a possible substrate for tissue amine oxidase activity have resulted in the ultracytochemical localization of enzyme oxidase activity referred to as DAPA oxidase (DAPAO). DAPA was designed with the goal of providing an amine that would yield on oxidation a stronger reducing aldehyde than does tryptamine in the histochemical demonstration of monoamine oxidase (MAO) with tetrazolium salts.Ultracytochemical preparations of guinea pig heart, liver and kidney and rat heart and liver were studied. Guinea pig kidney, known to exhibit high levels of MAO, appeared the most reactive of the tissues studied. DAPAO reaction product appears primarily in mitochondrial outer compartments and cristae (Figs. 2-4). Reaction product is also localized in endoplasmic reticulum, cytoplasmic vacuoles and nuclear envelopes (Figs. 2 and 3) and in the sarcoplasmic reticulum of heart.

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MRI, Clinical, and Biochemical Features of Partial Pyruvate Carboxylase Deficiency

Journal of Child Neurology ◽

10.1177/088307389400900421 ◽

1994 ◽

Vol 9 (4) ◽

pp. 436-439 ◽

Cited By ~ 19

Author(s):

Joseph J. Higgins ◽

Allen M. Glasgow ◽

Marilyn Lusk ◽

Douglas S. Kerr

Keyword(s):

Pyruvate Carboxylase ◽

Pyruvate Carboxylase Deficiency ◽

Biochemical Features

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Peroxisomal-mitochondrial oxidation in a rodent model of obesity-associated insulin resistance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00399.2006 ◽

2007 ◽

Vol 293 (4) ◽

pp. E986-E1001 ◽

Cited By ~ 46

Author(s):

Robert C. Noland ◽

Tracey L. Woodlief ◽

Brian R. Whitfield ◽

Steven M. Manning ◽

Jasper R. Evans ◽

...

Keyword(s):

Insulin Resistance ◽

Clinical Importance ◽

Product Distribution ◽

Zucker Rats ◽

Acid Oxidation ◽

Insulin Resistant ◽

Malonyl Coa ◽

Skeletal Muscle Lipid ◽

Mitochondrial Oxidation ◽

Cpt I

Peroxisomal oxidation yields metabolites that are more efficiently utilized by mitochondria. This is of potential clinical importance because reduced fatty acid oxidation is suspected to promote excess lipid accumulation in obesity-associated insulin resistance. Our purpose was to assess peroxisomal contributions to mitochondrial oxidation in mixed gastrocnemius (MG), liver, and left ventricle (LV) homogenates from lean and fatty ( fa/fa) Zucker rats. Results indicate that complete mitochondrial oxidation (CO2production) using various lipid substrates was increased approximately twofold in MG, unaltered in LV, and diminished ∼50% in liver of fa/fa rats. In isolated mitochondria, malonyl-CoA inhibited CO2production from palmitate 78%, whereas adding isolated peroxisomes reduced inhibition to 21%. These data demonstrate that peroxisomal products may enter mitochondria independently of CPT I, thus providing a route to maintain lipid disposal under conditions where malonyl-CoA levels are elevated, such as in insulin-resistant tissues. Peroxisomal metabolism of lignoceric acid in fa/fa rats was elevated in both liver and MG (LV unaltered), but peroxisomal product distribution varied. A threefold elevation in incomplete oxidation was solely responsible for increased hepatic peroxisomal oxidation (CO2unaltered). Alternatively, only CO2was detected in MG, indicating that peroxisomal products were exclusively partitioned to mitochondria for complete lipid disposal. These data suggest tissue-specific destinations for peroxisome-derived products and emphasize a potential role for peroxisomes in skeletal muscle lipid metabolism in the obese, insulin-resistant state.

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Rat liver pyruvate carboxylase. V. Reversible dissociation by chloride salts of monovalent cations.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)42019-x ◽

1975 ◽

Vol 250 (1) ◽

pp. 331-336

Author(s):

K Nakashima ◽

F B Rudolph ◽

T Wakabayashi ◽

H A Lardy

Keyword(s):

Rat Liver ◽

Pyruvate Carboxylase ◽

Monovalent Cations ◽

Reversible Dissociation ◽

Chloride Salts

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Heart failure—emerging roles for the mitochondrial pyruvate carrier

Cell Death and Differentiation ◽

10.1038/s41418-020-00729-0 ◽

2021 ◽

Author(s):

Mariana Fernandez-Caggiano ◽

Philip Eaton

Keyword(s):

Heart Failure ◽

Warburg Effect ◽

Translational Regulation ◽

Hypertrophic Growth ◽

Metabolic Adaptations ◽

Mitochondrial Pyruvate Carrier ◽

Heart Failure Progression ◽

Mitochondrial Oxidation ◽

Human And Mouse ◽

The Warburg Effect

AbstractThe mitochondrial pyruvate carrier (MPC) is the entry point for the glycolytic end-product pyruvate to the mitochondria. MPC activity, which is controlled by its abundance and post-translational regulation, determines whether pyruvate is oxidised in the mitochondria or metabolised in the cytosol. MPC serves as a crucial metabolic branch point that determines the fate of pyruvate in the cell, enabling metabolic adaptations during health, such as exercise, or as a result of disease. Decreased MPC expression in several cancers limits the mitochondrial oxidation of pyruvate and contributes to lactate accumulation in the cytosol, highlighting its role as a contributing, causal mediator of the Warburg effect. Pyruvate is handled similarly in the failing heart where a large proportion of it is reduced to lactate in the cytosol instead of being fully oxidised in the mitochondria. Several recent studies have found that the MPC abundance was also reduced in failing human and mouse hearts that were characterised by maladaptive hypertrophic growth, emulating the anabolic scenario observed in some cancer cells. In this review we discuss the evidence implicating the MPC as an important, perhaps causal, mediator of heart failure progression.

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