scholarly journals The effect of starvation and starvation followed by feeding on enzyme activity and the metabolism of [U−14C]glucose in liver from growing chicks

1968 ◽  
Vol 108 (4) ◽  
pp. 667-673 ◽  
Author(s):  
Alan G. Goodridge
Keyword(s):  
Fatty Acids ◽  
Enzyme Activity ◽  
Fatty Acid ◽  
Isocitrate Dehydrogenase ◽  
Malic Enzyme ◽  
Acid Synthesis ◽  
Minor Role ◽  
Hexose Monophosphate ◽  
Hexose Monophosphate Shunt ◽  
Cleavage Enzyme

1. The conversion of [U−14C]glucose into carbon dioxide, cholesterol and fatty acids in liver slices and the activities of ‘malic’ enzyme, citrate-cleavage enzyme, NADP-linked isocitrate dehydrogenase and hexose monophosphate-shunt dehydrogenases in the soluble fraction of homogenates of liver were measured in chicks that were starved or starved then fed. 2. In newly hatched chicks the incorporation of [U−14C]glucose and the activity of ‘malic’ enzyme did not increase unless the birds were fed. The response to feeding of [U−14C]glucose incorporation into fatty acids increased as the starved chicks grew older. 3. Citrate-cleavage enzyme activity increased slowly even when the newly hatched chicks were unfed. On feeding, citrate-cleavage enzyme activity increased at a much faster rate. 4. In normally fed 20-day-old chicks starvation decreased the incorporation of [U−14C]glucose into all three end products and depressed the activities of ‘malic’ enzyme and citrate-cleavage enzyme. Re-feeding increased all of these processes to normal or higher-than-normal levels. 5. In both newly hatched and 20-day-old chicks starvation increased the activity of isocitrate dehydrogenase and feeding or re-feeding decreased it. 6. Very little change in hexose monophosphate-shunt dehydrogenase activity was observed during the dietary manipulations. 7. The results indicate that increased substrate delivery to the liver is the principal stimulus to the increased rate of glucose metabolism observed in newly hatched chicks. The results also suggest that changes in the activities of ‘malic’ enzyme and citrate-cleavage enzyme are secondary to an increased flow of metabolites through the glucose-to-fatty acid pathway and that the dehydrogenases of the hexose monophosphate shunt play a minor role in NADPH production for fatty acid synthesis.

The effects of dietary fat on fatty acid synthesis and malic enzyme activity in liver from growing chicks

1969 ◽  
Vol 47 (7) ◽  
pp. 743-746 ◽  
Author(s):  
Alan G. Goodridge
Keyword(s):  
Fatty Acids ◽  
Enzyme Activity ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Dietary Fat ◽  
Malic Enzyme ◽  
Corn Oil ◽  
Acid Synthesis ◽  
Hepatic Lipogenesis ◽  
Malic Enzyme Activity

Hepatic malic enzyme activity and incorporation of glucose-U-14C into fatty acids in liver slices was no greater in birds fed fat-free diets than in those fed the same diets supplemented with corn oil. The results suggest that in the chick, in contrast to the rat, dietary fat does not suppress hepatic lipogenesis.

scholarly journals Citrate-cleavage enzyme, ‘malic’ enzyme and certain dehydrogenases in embryonic and growing chicks

1968 ◽  
Vol 108 (4) ◽  
pp. 663-666 ◽  
Author(s):  
Alan G. Goodridge
Keyword(s):  
Adipose Tissue ◽  
Malic Enzyme ◽  
Fold Increase ◽  
Hexose Monophosphate ◽  
Hexose Monophosphate Shunt ◽  
Glycerophosphate Dehydrogenase ◽  
Cleavage Enzyme ◽  
Malic Enzyme Activity ◽  
Relationship Of

The activities of several enzymes possibly implicated in lipogenesis were measured in the soluble fraction of homogenates of liver and adipose tissue of embryonic and growing chicks. The activities of adipose-tissue enzymes showed little or no change. The activities of hepatic hexose monophosphate-shunt dehydrogenases, malate dehydrogenase, 3-phosphoglyceraldehyde dehydrogenase and NAD-linked α-glycerophosphate dehydrogenase also showed little or no change. Isocitrate dehydrogenase activity in liver rose to a peak on the day of hatching and fell to half the peak value during the next 12 days, where it remained to 26 days after hatching. The activities of ‘malic’ enzyme and citrate-cleavage enzyme showed very low stable values in embryonic liver and remarkable rises during the early part of the post-hatching period. An 85-fold increase in the activity of ‘malic’ enzyme activity was completed in 7 days and a 15-fold increase in that of citrate-cleavage enzyme in 5 days. The activities then attained were maintained up to 26 days after hatching. 2. The increases in the activities of hepatic citrate-cleavage enzyme and ‘malic’ enzyme occurred simultaneously with a marked increase in lipogenesis, suggesting a relationship of these enzymes to lipogenesis in chick liver. By contrast, activity of the hexose monophosphate-shunt dehydrogenases does not appear to be thus associated.

scholarly journals FSMP-15. EVALUATING THE ROLE OF LONG-CHAIN FATTY ACID METABOLISM IN PROMOTING GLIOBLASTOMA GROWTH

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i19-i19
Author(s):  
Divya Ravi ◽  
Carmen del Genio ◽  
Haider Ghiasuddin ◽  
Arti Gaur
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Survival Rate ◽  
Tumor Progression ◽  
Acid Synthesis ◽  
Normal Brain ◽  
Acid Uptake ◽  
Exogenous Fatty Acid ◽  
Long Chain

Abstract Glioblastomas (GBM) or Stage IV gliomas, are the most aggressive of primary brain tumors and are associated with high mortality and morbidity. Patients diagnosed with this lethal cancer have a dismal survival rate of 14 months and a 5-year survival rate of 5.6% despite a multimodal therapeutic approach, including surgery, radiation therapy, and chemotherapy. Aberrant lipid metabolism, particularly abnormally active de novo fatty acid synthesis, is recognized to have a key role in tumor progression and chemoresistance in cancers. Previous studies have reported a high expression of fatty acid synthase (FASN) in patient tumors, leading to multiple investigations of FASN inhibition as a treatment strategy. However, none of these have developed as efficacious therapies. Furthermore, when we profiled FASN expression using The Cancer Genome Atlas (TCGA) we determined that high FASN expression in GBM patients did not confer a worse prognosis (HR: 1.06; p-value: 0.51) and was not overexpressed in GBM tumors compared to normal brain. Therefore, we need to reexamine the role of exogenous fatty acid uptake over de novofatty acid synthesis as a potential mechanism for tumor progression. Our study aims to measure and compare fatty acid oxidation (FAO) of endogenous and exogenous fatty acids between GBM patients and healthy controls. Using TCGA, we have identified the overexpression of multiple enzymes involved in mediating the transfer and activation of long-chain fatty acids (LCFA) in GBM tumors compared to normal brain tissue. We are currently conducting metabolic flux studies to (1) assess the biokinetics of LCFA degradation and (2) establish exogenous versus endogenous LCFA preferences between patient-derived primary GBM cells and healthy glial and immune cells during steady state and glucose-deprivation.

scholarly journals A novel acyl-CoA-binding protein from bovine liver. Effect on fatty acid synthesis

1987 ◽  
Vol 241 (1) ◽  
pp. 189-192 ◽  
Author(s):  
I B Mogensen ◽  
H Schulenberg ◽  
H O Hansen ◽  
F Spener ◽  
J Knudsen
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Binding Protein ◽  
Fatty Acid Synthetase ◽  
Bovine Liver ◽  
Acid Synthesis ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding ◽  
Medium Chain ◽  
Chain Acyl

Bovine liver was shown to contain a hitherto undescribed medium-chain acyl-CoA-binding protein. The protein co-purifies with fatty-acid-binding proteins, but was, unlike these proteins, unable to bind fatty acids. The protein induced synthesis of medium-chain acyl-CoA esters on incubation with goat mammary-gland fatty acid synthetase. The possible function of the protein is discussed.

scholarly journals The regulation of glyceride synthesis in isolated white-fat cells. The effects of palmitate and lipolytic agents

1972 ◽  
Vol 128 (5) ◽  
pp. 1057-1067 ◽  
Author(s):  
E. D Saggerson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Fat Cells ◽  
Glyceride Synthesis ◽  
Glucose Incorporation ◽  
High Concentrations ◽  
Stimulation Of

1. 0.5mm-Palmitate stimulated incorporation of [U-14C]glucose into glyceride glycerol and fatty acids in normal fat cells in a manner dependent upon the glucose concentration. 2. In the presence of insulin the incorporation of 5mm-glucose into glyceride fatty acids was increased by concentrations of palmitate, adrenaline and 6-N-2′-O-dibutyryladenosine 3′:5′-cyclic monophosphate up to 0.5mm, 0.5μm and 0.5mm respectively. Higher concentrations of these agents produced progressive decreases in the rate of glucose incorporation into fatty acids. 3. The effects of palmitate and lipolytic agents upon the measured parameters of glucose utilization were similar, suggesting that the effects of lipolytic agents are mediated through increased concentrations of free fatty acids. 4. In fat cells from 24h-starved rats, maximal stimulation of glucose incorporation into fatty acids was achieved with 0.25mm-palmitate. Higher concentrations of palmitate were inhibitory. In fat cells from 72h-starved rats, palmitate only stimulated glucose incorporation into fatty acids at high concentrations of palmitate (1mm and above). 5. The ability of fat cells to incorporate glucose into glyceride glycerol in the presence of palmitate decreased with increasing periods of starvation. 6. It is suggested that low concentrations of free fatty acids stimulate fatty acid synthesis from glucose by increasing the utilization of ATP and cytoplasmic NADH for esterification of these free fatty acids. When esterification of free fatty acids does not keep pace with their provision, inhibition of fatty acid synthesis occurs. Provision of free fatty acids far in excess of the esterification capacity of the cells leads to uncoupling of oxidative phosphorylation and a secondary stimulation of fatty acid synthesis from glucose.

scholarly journals Synthesis of fatty acids in the perfused mouse liver

1974 ◽  
Vol 142 (3) ◽  
pp. 611-618 ◽  
Author(s):  
D. Michael W. Salmon ◽  
Neil L. Bowen ◽  
Douglas A. Hems
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Saturated Fatty Acids ◽  
Carbon Sources ◽  
Acid Synthesis ◽  
Hepatic Glycogen ◽  
Total Rate ◽  
Glucose Carbon

1. Fatty acid synthesis de novo was measured in the perfused liver of fed mice. 2. The total rate, measured by the incorporation into fatty acid of3H from3H2O (1–7μmol of fatty acid/h per g of fresh liver), resembled the rate found in the liver of intact mice. 3. Perfusions with l-[U-14C]lactic acid and [U-14C]glucose showed that circulating glucose at concentrations less than about 17mm was not a major carbon source for newly synthesized fatty acid, whereas lactate (10mm) markedly stimulated fatty acid synthesis, and contributed extensive carbon to lipogenesis. 4. The identification of 50% of the carbon converted into newly synthesized fatty acid lends further credibility to the use of3H2O to measure hepatic fatty acid synthesis. 5. The total rate of fatty acid synthesis, and the contribution of glucose carbon to lipogenesis, were directly proportional to the initial hepatic glycogen concentration. 6. The proportion of total newly synthesized lipid that was released into the perfusion medium was 12–16%. 7. The major products of lipogenesis were saturated fatty acids in triglyceride and phospholipid. 8. The rate of cholesterol synthesis, also measured with3H2O, expressed as acetyl residues consumed, was about one-fourth of the basal rate of fatty acid synthesis. 9. These results are discussed in terms of the carbon sources of hepatic newly synthesized fatty acids, and the effect of glucose, glycogen and lactate in stimulating lipogenesis, independently of their role as precursors.

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