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Biomedical subjects

A Szutowicz

Publications and source records attributed to A Szutowicz.

At least 55 records · Page 3Linked to original sources
PubMed1982

ATP citrate lyase in cholinergic nerve endings.

The activity of ATP-citrate lyase in homogenates of five selected rat brain regions varied from 2.93 to 6.90 nmol/min/mg of protein in the following order: cerebellum less than hippocampus less than parietal cortex less than striatum less than medulla oblongata and that of the choline acetyltransferase from 0.15 to 2.08 nmol/min/mg of protein in cerebellum less than parietal cortex less than hippocampus = medulla oblongata less than striatum. No substantial differences were found in regional activities of lactate dehydrogenase, pyruvate dehydrogenase, citrate synthase or acetyl-CoA synthase. High values of relative specific activities for both choline acetyltransferase and ATP-citrate lyase were found in synaptosomal and synaptoplasmic fractions from regions with a high content of cholinergic nerve endings. There are significant correlations between these two enzyme activities in general cytocol (S3), synaptosomal (B) and synaptoplasmic (Bs) fractions from the different regions (r = 0.92-0.99). These data indicate that activity of ATP-citrate lyase in cholinergic neurons is several times higher than that present in glial and noncholinergic neuronal cells.

ATP Citrate (pro-S)-Lyase↗
PubMed1982

Effects of septal lesions on enzymes of acetyl-CoA metabolism in the cholinergic system of the rat hippocampus.

Electrolytic lesions made in the medial septum of the rat brain caused an 80% decrease in the activity of choline acetyltransferase and a 33% reduction in ATP-citrate lyase activity in the synaptosomal fraction from the hippocampus. Decreases in the activities of the two enzymes in the cytosol (S3) fraction were 70 and 13%, respectively. The activities of pyruvate dehydrogenase, citrate synthase, acetyl-CoA synthase, and carnitine acetyltransferase in crude hippocampal homogenates and in subcellular fractions were not affected by septal lesions. The data indicate that ATP-citrate lyase is linked to the septal-hippocampal pathway and that the enzyme is preferentially located in cholinergic nerve endings that terminate within the hippocampus.

ATP Citrate (pro-S)-Lyase↗
PubMed1982

The contribution of citrate to the synthesis of acetyl units in synaptosomes of developing rat brain.

The activities of pyruvate dehydrogenase, citrate synthase, and choline acetyltransferase in rat brain synaptosomes increased during ontogenesis by 3 and 14 times, respectively. Activity of ATP-citrate lyase decreased by 26% during the same period. Pyruvate consumption by synaptosomes from 1-day-old animals was 40% lower than that found in older rats; however, citrate efflux from intrasynaptosomal mitochondria in immature synaptosomes was over twice as high as that in mature ones. The rates on production of synaptoplasmic acetyl-CoA by ATP-citrate lyase were 1.03, 1.40, and 0.49 nmol/min/mg protein in 1-, 10-day-old, and adult rats, respectively. 3-Bromopyruvate (0.5 mM) inhibited pyruvate consumption by 70% and caused a complete block of citrate utilization by citrate lyase in every age group. Parameters of citrate metabolism in cerebellar synaptosomes were the same as those in cerebral ones. These data indicate that production of acetyl-CoA from citrate in synaptoplasm may be regulated either by adaptative, age-dependent changes in permeability and carrier capacity of the mitochondrial membrane or by the inhibition of synthesis of intramitochondrial acetyl-CoA. ATP-citrate lyase activity is not a rate-limiting factor in this process. Metabolic fluxes of pyruvate to cytoplasmic citrate and acetyl-CoA are presumably the same in both cholinergic and noncholinergic nerve endings. The significance of citrate release from intrasynaptosomal mitochondria as a regulatory step in acetylcholine synthesis is discussed.

ATP Citrate (pro-S)-Lyase↗
PubMed1980

Regional and subcellular distribution of ATP-citrate lyase and other enzymes of acetyl-CoA metabolism in rat brain.

The activities of ATP-citrate lyase in frog, guinea pig, mouse, rat, and human brain vary from 18 to 30 mu mol/h/g of tissue, being several times higher than choline acetyltransferase activity. Activities of pyruvate dehydrogenase and acetyl coenzyme A synthetase in rat brain are 206 and 18.4 mu mol/h/g of tissue, respectively. Over 70% of the activities of both choline acetyltransferase and ATP-citrate lyase in secondary fractions are found in synaptosomes. Their preferential localization in synaptosomes and synaptoplasm is supported by RSA values above 2. Acetyl CoA synthetase activity is located mainly in whole brain mitochondria (RSA, 2.33) and its activity in synaptoplasm is low (RSA, 0.25). The activities of pyruvate dehydrogenase, citrate synthase, and carnitine acetyltransferase are present mainly in fractions C and Bp. No pyruvate dehydrogenase activity is found in synaptoplasm. Striatum, cerebral cortex, and cerebellum contain similar activities of pyruvate dehydrogenase, citrate synthase, carnitine acetyltransferase, fatty acid synthetase, and acetyl-CoA hydrolase. Activities of acetyl CoA synthetase, choline acetyltransferase and ATP-citrate lyase in cerebellum are about 10 and 4 times lower, respectively, than in other parts of the brain. These data indicate preferential localization of ATP-citrate lyase in cholinergic nerve endings, and indicate that this enzyme is not a rate limiting step in the synthesis of the acetyl moiety of ACh in brain.

ATP Citrate (pro-S)-Lyase↗
PubMed1979

Lipogenetic and glycolytic enzyme activities in carcinoma and nonmalignant diseases of the human breast.

Activities of some enzymes associated with carbohydrate and lipid metabolism were determined in 48 human breast carcinomas and compared with those found in 35 nonmalignant breast tumours and also in 13 normal breast tissues. In fibrocystic disease only the activity of citrate lyase was markedly higher (14-fold) than in normal tissue. The activities of the remaining enzymes did not differ significantly from those in normal tissue. Enzyme activities in breast carcinoma were 4--160 x those determined in normal tissue according to the following sequence : phosphofructokinase less than malate NADP dehydrogenase less than hexokinase less than lactate dehydrogenase less than isocitrate NADP dehydrogenase less than ATP citrate lyase. Activity of citrate lyase, very low in normal breast (0.0017 mumol/min/g of tissue) rose gradually to 0.039, 0.072 and 0.258 mumol/min/g of tissue in localized fibrocystic disease, fibroadenomas and carcinomas respectively. These data support the idea that citrate lyase may play an important role in lipogenesis in hyperplastic human breast tissues.

Breast↗
PubMed1976

Subcellular localization of nerve growth factor receptors. Thirteen-day chick embryo brain.

The subcellular location of the specific binding sites of nerve growth factor (NGF) as judged by binding of the 125I-labeled protein in 13-day chick embryo brain, has been examined. The homogenized tissue was separated into four fractions, P1, P2, P3, and S, by differential centrifugation. Fraction P2, which contained the majority of the specific 125I-NGF binding, was further separated by discontinuous sucrose density gradient centrifugation into three fractions. Fraction B contains many synaptosome-like structures, which, when derived from adult brain, result from the shearing off and resealing of synaptic terminals. This fraction contained 65% of the specific 125I-NGF binding of P2. Following hypoosmotic lysis by water, Fraction B was separated into seven fractions, O, D, E, F, G, H, and I, by discontinuous sucrose density gradient centrifugation. The specific 125I-NGF binding was localized with the denser fractions, G, H, and I, with about a 10-fold purification as compared to the original homogenate. However, only 65% of the binding of Fraction B was found in the sum of the tertiary fractions, indicating that some loss of specific binding accompanied the lysis. By means of marker enzymes and macromolecules, as well as electron microscopy, it was determined that the distribution of cellular components of embryonic tissue in this fractionation technique is very similar to that observed for adult brain tissue. Thus, the properties of the NGF receptors determined in whole brain, which are remarkably similar to those found in peripheral neurons, are the properties of the receptors that appear to be located in the developing synaptosomal structures.

Animals↗
PubMed1976

Subcellular localization of nerve growth factor receptors. Developmental correlations in chick embryo brain.

The subcellular distribution of receptors for nerve growth factor (NGF), as assayed by specific binding of the 125I-labeled protein, during the embryonic development of chick brain has been examined. Utilizing differential centrifugation and discontinuous sucrose density gradient centrifugation, it was observed that the majority of the specific NGF receptors are localized in the crude (P2) and purified (B) synaptosomal fractions at all stages of brain development examined. However, during early stages (day 6 to 8) a significant portion of the receptors are also found in the P1 fraction, consistent with their location on dense subcellular structures. Significant 125I-NGF binding is observed in this period of development before the appearance of neurochemical markers (choline acetyltransferase, dopamine-beta-hydroxylase, and 125I-alpha-bungarotoxin binding) which are associated with synaptosomes. The latter stages of development, particularly days 13 to 18, show parallel rapid increases in all neurochemical markers and 125I-NGF binding consistent with the association of nearly all late appearing NGF receptors with synaptosomes. These two apparent classes of NGF receptors may have distinct functional roles in the embryonic development of the chick brain.

Animals↗
PubMed1976

Pyruvate metabolism in rat brain mitochondria.

1. Oxidation of pyruvate by rat brain mitochondria was stimulated in state 3 by malate or succinate up to 250 nmoles O2/mg protein/min. Oxidation of malate, succinate, 2-oxoglutarate or glutamate as the sole substrates, was 1/4 - 1/5 that observed with pyruvate. 2. Maximum oxygen consumption in state 3 was observed at pH 6.90 - 7.20, whereas in state 4 it was not affected by changes in pH. 3. In state 4, in the absence of exogenous acceptor or acetyl residues, acetate was the main oxidation product, corresponding to about 80% of the amount of pyruvate utilized. Malate did not affect the rate of pyruvate utilization but lowered acetate concentration and raised concentration of citrate and 2-oxoglutarate. 4. In state 3, pyruvate and malate were converted mainly to 2-oxoglutarate, its concentration being three times as high as that of citrate. 5. Formation of citrate, 2-oxoglutarate and acetate from pyruvate in brain is considered as a function of availability of the acceptor of acetyl residues and the energy state of mitochondrion.

Adenosine Triphosphate↗
PubMed1976

Effect of (-)hydroxycitrate on the activities of ATP citrate lyase and the enzymes of acetyl-CoA metabolism in rat brain.

1. (-)Hyrdoxycitrate is a potent inhibitor of ATP citrate (pro-3S)lyase (EC 4.1.3.8) from rat brain, the inhibition being uncompetitive with respect to MgATP2-and competitive with citrate (Ki 0.8 muM). 2. The rate of oxygen consumption by rat brain synaptosomes and the activities of fatty acid synthetase, carnitine acetyltransferase, glucose-6-phosphate dehydrogenase and acetyl-CoA-synthetase are not affected by (-)hydroxycitrate. 3. (-)Hydroxycitrate inhibits the activities of isocitrate dehydrogenase, malate dehydrogenase (decarboxylating) and aconitate hydratase at millimolar concentrations.

ATP Citrate (pro-S)-Lyase↗
PubMed1975

Effect of bicarbonate buffer on the activity of cytoplasmic and mitochondrial alanine aminotransferase.

1. Bicarbonate stimulates the activity of rat brain cytoplasmic and mitochondrial alanine aminotransferase (EC 2.6.1.2) probably due to the enhanced affinity for its substrates. 2. Under the same conditions, the activity of crystalline aspartate aminotransferase was inhibited. 3. The role of bicarbonate buffer in regulation of alanine aminotransferase activity and synthesis of alanine are discussed.

Alanine Transaminase↗