The effects of pregnancy, lactation and involution on the metabolism of glucose and acetate by rat liver tissue

SummaryThe incorporation of 14C from [1-14C] and [6-14C]glucose and [2-14C]acetate into CO2 and fatty acids by rat liver slices was measured at intervals during pregnancy, lactation and involution.During late pregnancy, the rates of oxidation of the C-1 and C-6 atoms of glucose were respectively 65 and 40 % higher than those for unmated animals. These increases were maintained during lactation, but the highest values were observed 3 days after weaning. Pregnancy and lactation had little effect on the oxidation of [2-14C]acetate.The incorporation of14C from all 3 labelled substrates into fatty acids was increased by a factor of 3–4 during late pregnancy. There were further increases during lactation, and 3 days after weaning the values were as much as 10 times as high as those for unmated animals.The incorporation of both [14C]glucose and [14C]acetate into cholesterol was increased by a factor of 6–7 during lactation.The activities of the enzymes glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, ATP citrate lyase and acetyl-CoA carboxylase were also increased during lactation and involution.The similarity between the changes summarized above and those brought about by changes in the pattern of food intake is discussed, and the idea that fatty acids synthesized from non-lipid precursors in the liver may make some contribution to the formation of milk fat is also considered.

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Changes in activity of some enzymes involved in glucose utilization and formation in developing rat liver

Biochemical Journal ◽

10.1042/bj1060321 ◽

1968 ◽

Vol 106 (2) ◽

pp. 321-329 ◽

Cited By ~ 78

Author(s):

R. G. Vernon ◽

D G Walker

Keyword(s):

Malate Dehydrogenase ◽

Rat Liver ◽

Postnatal Period ◽

Supernatant Fraction ◽

Atp Citrate Lyase ◽

Carboxylase Activity ◽

Phosphogluconate Dehydrogenase ◽

Citrate Lyase ◽

Glucose 6 Phosphate Dehydrogenase ◽

Developing Rat

1. The activities of some enzymes involved in both the utilization of glucose (pyruvate kinase, ATP citrate lyase, NADP-specific malate dehydrogenase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP-specific isocitrate dehydrogenase, all present in the supernatant fraction of liver homogenates) and the formation of glucose by gluconeogenesis (glucose 6-phosphatase in the whole homogenate and fructose 1,6-diphosphatase, phosphopyruvate carboxylase, NAD-specific malate dehydrogenase and fumarase in the supernatant fraction) have been determined in rat liver around birth and in the postnatal period until the end of weaning. 2. The activities of those enzymes involved in the conversion of glucose into lipid are low during the neonatal period and increase with weaning. NADP-specific malate dehydrogenase first appears and develops at the beginning of the weaning period. 3. The marked increase in cytoplasmic phosphopyruvate carboxylase activity at birth is probably the major factor initiating gluconeogenesis at that time. 4. The results are discussed against the known changes in dietary supplies and the known metabolic patterns during the period of development.

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Response of lipogenic enzymes to overfeeding in liver and adipose tissue of light and heavy breeds of chicks

British Journal Of Nutrition ◽

10.1079/bjn19780021 ◽

1978 ◽

Vol 39 (1) ◽

pp. 151-157 ◽

Cited By ~ 24

Author(s):

Niva Shapira ◽

I. Nir ◽

P. Budowski

Keyword(s):

Adipose Tissue ◽

Fatty Acid Synthetase ◽

Fat Content ◽

Acetyl Coa Carboxylase ◽

Lipogenic Enzymes ◽

Atp Citrate Lyase ◽

Phosphogluconate Dehydrogenase ◽

Citrate Lyase ◽

Generating Capacity ◽

Glucose 6 Phosphate Dehydrogenase

1. Chicks, 3-d-old, of a heavy breed (HB) and a light breed (LB) were overfed for 18 d. The activities of acetyl-CoA carboxylase (EC 6.4.1.2; CBX), fatty acid synthetase (FAS), ATP citrate lyase (EC 4.1.3.8; CCE), NADP-malate dehydrogenase (decarboxylating) (EC 1.1.1.40; ME), 6-glucose-6-phosphate dehydrogenase (EC 1.1.1.49; G6PDH) and phosphogluconate dehydrogenase (EC 1.1.1.44; 6PGDH) were determined in abdominal adipose tissue (AT) and liver samples of overfed and ad lib.-fed chicks. Size and fat content of liver and adipose tissue were also determined in order to evaluate the extent of obesity.2. On ad lib.-feeding HB chicks consumed more food, gained more weight and deposited more fat than the corresponding LB chicks. Their lipogenic enzymes were more active than in the LB chicks in both adipose tissue and liver. The increase in food consumption (%) that could be achieved by overfeeding was three times greater in the LB chicks than in the HB chicks.3. Overfeeding increased the weight and fat content of liver and AT in both breeds. The specific activities of CBX, FAS, CCE and ME in liver and AT increased in the LB chicks only and the total activities of liver and AT enzymes increased much more in the LB chicks than in the HB chicks in which the increase was derived mainly from tissue enlargement.4. The activity of the pentose cycle dehydrogenases was very low in liver, but in AT about one third of the NADPH generating capacity could be accounted for by these dehydrogenases.5. The results show that lipogenic enzymes of chicks respond to an increased substrate flux. It is suggested that the enlarged liver, the higher participation of AT in lipogenesis and the uninterrupted supply of cropstored excess food enable the chick to accommodate the increased amounts of substrate with only moderate enzymic adaptation.

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Variations in the activity of several enzymes in the mammary glands of non-pregnant, pregnant and lactating rabbits

Biochemical Journal ◽

10.1042/bj1160657 ◽

1970 ◽

Vol 116 (4) ◽

pp. 657-661 ◽

Cited By ~ 8

Author(s):

P. E. Hartmann ◽

E. A. Jones

Keyword(s):

Mammary Gland ◽

Small Mammals ◽

Enzyme Activities ◽

Mammary Glands ◽

Acetyl Coa Carboxylase ◽

Atp Citrate Lyase ◽

Acetyl Coa ◽

Phosphogluconate Dehydrogenase ◽

Citrate Lyase ◽

Lactation Cycle

1. The enzymes phosphofructokinase (EC 2.7.1.11), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), phosphoglucomutase (EC 2.7.5.1), ATP–citrate lyase (EC 4.1.3.8), acetyl-CoA carboxylase (EC 6.4.1.2) and acetyl-CoA synthetase (EC 6.2.1.1) were assayed in rabbit mammary glands at various stages of the pregnancy–lactation cycle. 2. The activities of all enzymes were low during pregnancy and, with the exception of phosphofructokinase, in non-pregnant animals. Two- to ten-fold increases in enzyme activities occurred over the first 20 days of lactation. Although milk yield was considerably decreased, the enzyme activities remained elevated in late lactation (45 days after parturition). 3. These findings are discussed in relation to mammary-gland metabolism and compared with similar observations previously made on ruminants and other small mammals.

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The effects of pregnancy, lactation and involution on the metabolism of glucose by rat parametrial adipose tissue

Journal of Dairy Research ◽

10.1017/s0022029900014722 ◽

1973 ◽

Vol 40 (3) ◽

pp. 353-360 ◽

Cited By ~ 16

Author(s):

R. W. Smith

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Fatty Acid ◽

Acid Synthesis ◽

Fat Depots ◽

Phosphogluconate Dehydrogenase ◽

Total Body Fat ◽

Pregnancy And Lactation ◽

Total Body ◽

Glucose 6 Phosphate Dehydrogenase

SummaryThe incorporation of 14C from [1-14C] and [6-14C]glucose into CO2, fatty acids and glycerol by rat parametrial adipose tissue was measured at intervals during pregnancy, lactation and involution. There were small increases in the incorporation of both the C-1 and C-6 atoms into CO2 and glycerol on the seventh and sixteenth days of pregnancy. Fatty acid synthesis from glucose was negligible on the twentieth day of pregnancy and during lactation. Three days after weaning the rate of oxidation of the C-1 atom was doubled and the incorporation of both carbon atoms into fatty acids was increased at least 20-fold. There were no changes in the activities of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase during pregnancy and lactation, but 3 days after weaning the activities of both enzymes were doubled. These results are discussed in relation to other evidence that the total body fat is increased during pregnancy, and to the idea that the fat depots are mobilized during lactation.

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Adaptation to a high protein, carbohydrate-free diet induces a marked reduction of fatty acid synthesis and lipogenic enzymes in rat adipose tissue that is rapidly reverted by a balanced diet

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y05-035 ◽

2005 ◽

Vol 83 (6) ◽

pp. 477-482 ◽

Cited By ~ 3

Author(s):

S M.R.C Brito ◽

M A.F Moura ◽

N H Kawashita ◽

W T.L Festuccia ◽

M A.R Garófalo ◽

...

Keyword(s):

Adipose Tissue ◽

Pyruvate Dehydrogenase Complex ◽

Acid Synthesis ◽

High Protein ◽

Acetyl Coa Carboxylase ◽

Atp Citrate Lyase ◽

Balanced Diet ◽

Citrate Lyase ◽

Glucose 6 Phosphate Dehydrogenase

We have previously shown that in vivo lipogenesis is markedly reduced in liver, carcass, and in 4 different depots of adipose tissue of rats adapted to a high protein, carbohydrate-free (HP) diet. In the present work, we investigate the activity of enzymes involved in lipogenesis in the epididymal adipose tissue (EPI) of rats adapted to an HP diet before and 12 h after a balanced diet was introduced. Rats fed an HP diet for 15 days showed a 60% reduction of EPI fatty acid synthesis in vivo that was accompanied by 45%–55% decreases in the activities of pyruvate dehydrogenase complex, ATP-citrate lyase, acetyl-CoA carboxylase, glucose-6-phosphate dehydrogenase, and malic enzyme. Reversion to a balanced diet for 12 h resulted in a normalization of in vivo EPI lipogenesis, and in a restoration of acetyl-CoA carboxylase activity to levels that did not differ significantly from control values. The activities of ATP-citrate lyase and pyruvate dehydrogenase complex increased to about 75%–86% of control values, but the activities of glucose-6-phosphate dehydrogenase and malic enzyme remained unchanged 12 h after diet reversion. The data indicate that in rats, the adjustment of adipose tissue lipogenic activity is an important component of the metabolic adaptation to different nutritional conditions. Key words: lipogenesis, lipogenic enzymes, high protein diet, diet reversion.

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Factors involved in changes in hepatic lipogenesis during development of the rat

Biochemical Journal ◽

10.1042/bj1180155 ◽

1970 ◽

Vol 118 (1) ◽

pp. 155-162 ◽

Cited By ~ 49

Author(s):

Elizabeth A. Lockwood ◽

E. Bailey ◽

C. B. Taylor

Keyword(s):

Enzyme Activities ◽

Malic Enzyme ◽

Hormonal Control ◽

Male Rats ◽

Acetyl Coa Carboxylase ◽

Hepatic Enzymes ◽

Atp Citrate Lyase ◽

Acetyl Coa ◽

Citrate Lyase ◽

Glucose 6 Phosphate Dehydrogenase

1. Changes in the activities of acetyl-CoA carboxylase (EC 6.4.1.2), phosphofructokinase (EC 2.7.1.11), aldolase (EC 4.1.2.13), extramitochondrial aconitate hydratase (EC 4.2.1.3) and NADP-dependent isocitrate dehydrogenase (EC 1.1.1.42) have been measured in the livers of developing rats from late foetal life to maturity. 2. The effect of altering the weaning time on some enzymes associated with lipogenesis has been studied. Weaning rats at 15 days of age instead of 21 days results in an immediate increase in the activity of `malic' enzyme (EC 1.1.1.40) whereas the activities of glucose 6-phosphate dehydrogenase (EC 1.1.1.49) and ATP citrate lyase (EC 4.1.3.8) did not increase until 4–5 days and acetyl-CoA carboxylase 2–3 days after early weaning. Weaning rats on to an artificial-milk diet led to complete repression of the rise in activity of hepatic enzymes associated with lipogenesis normally found on weaning, except for `malic' enzyme, which increased in activity after 20 days of age. 3. The effect of intraperitoneal injections of glucagon, cortisol, growth hormone and thyroxine on the same hepatic enzymes has been investigated. Only thyroxine had any effect on enzyme activities and caused a 20-fold increase in `malic' enzyme activity and a twofold increase in ATP citrate lyase activity. 4. The activities of hepatic glucose 6-phosphate dehydrogenase and `malic' enzyme are higher in adult female than in adult male rats and it has been shown that this sex difference in enzyme activities is due to both male and female sex hormones. 5. Hepatic malate, citrate, pyruvate, glucose 6-phosphate and phosphoenolpyruvate concentrations have been measured throughout development. 6. The results are discussed in relation to the dietary and hormonal control of hepatic enzyme activities during development.

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The metabolic fate of the products of citrate cleavage. Adenosine triphosphate citrate lyase and nicotinamide–adenine dinucleotide phosphate-linked malate dehydrogenase in foetal and adult liver from ruminants and non-ruminants

Biochemical Journal ◽

10.1042/bj1080705 ◽

1968 ◽

Vol 108 (5) ◽

pp. 705-713 ◽

Cited By ~ 22

Author(s):

R. W. Hanson ◽

F. J. Ballard

Keyword(s):

Fatty Acids ◽

Malate Dehydrogenase ◽

Rat Liver ◽

Phosphoenolpyruvate Carboxykinase ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Atp Citrate Lyase ◽

Adult Rat ◽

Liver Slices ◽

Citrate Lyase ◽

Foetal Rat

1. Foetal rat liver slices incorporate the C-3 of aspartate and C-2 of glutamate into fatty acids at rates equal to those observed with adult rat liver slices. Incorporation of either of these labelled carbon atoms into fatty acids would require a functioning citrate-cleavage pathway which consists of the enzymes ATP–citrate lyase, NAD–malate dehydrogenase and NADP–malate dehydrogenase. However, NADP–malate dehydrogenase is present in foetal rat liver at only 5% of the activity detectable in adult rat liver. 2. From these findings and the effect of cofactors on the formation of 14CO2 from [1,5−14C2]citrate in liver supernatant fractions (100000g), it is suggested that NADP–malate dehydrogenase limits the citrate-cleavage sequence. 3. Measurement of the citrate-cleavage pathway by incorporation studies with [3−14C]aspartate and [U−14C]glucose and by determining the activities of ATP–citrate lyase and NADP–malate dehydrogenase have shown that this sequence of reactions is present in the liver of the bovine foetus but not in the adult. However, C-2 of glutamate is not incorporated into fatty acids or non-saponifiable lipid by bovine liver slices. This finding as well as those presented above for the adult and foetal rat liver are interpreted on the basis of a competition between phosphoenolpyruvate carboxykinase and NAD–malate dehydrogenase for oxaloacetate produced by the cleavage of citrate in the cytosol.

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Enzyme Activities of NADPH-Forming Metabolic Pathways in Normal and Leukemic Leukocytes

Clinical Chemistry ◽

10.1093/clinchem/21.7.880 ◽

1975 ◽

Vol 21 (7) ◽

pp. 880-883 ◽

Cited By ~ 5

Author(s):

Francesco Belfiore ◽

Vito Borzi ◽

Luigi Lo Vecchio ◽

Elena Napoli ◽

Agata M Rabuazzo

Keyword(s):

Malate Dehydrogenase ◽

Metabolic Pathways ◽

Normal Subjects ◽

Atp Citrate Lyase ◽

Phosphogluconate Dehydrogenase ◽

Myelocytic Leukemia ◽

Citrate Lyase ◽

Enzymatic Characteristic ◽

I Cells ◽

Low Activity

Abstract With respect to the enzymes of NADPH-forming metabolic pathways in human leukocytes: (a) Glucose-6phosphate dehydrogenase and phosphogluconate dehydrogenase (decarboxylating) were less active in leukocytes (mostly myeloblasts) from eight patients with acute myeloblastic leukemia (I) than in leukocytes (mostly granulocytes) from 16 normal subjects (II) or 16 patients with chronic myelocytic leukemia (III). (b) Of the enzymes of the citrate cleavage pathway, ATP citrate lyase and malate dehydrogenase (decarboxylating) (NADP+) were virtually absent in the cells studied. (c) Isocitrate dehydrogenase (NADP+), aspartate aminotransferase, and alanine aminotransferase, which, together with the much more active malate dehydrogenase, constitute a newly proposed NADPH-forming metabolic cycle, showed a higher activity in I than in II or III, and therefore could compensate, as concerns NADPHgeneration, for the low activity of pentose cycle dehydrogenases. We are not sure whether the enzymatic characteristic of I cells is attributable to their immaturity or to their leukemic nature.

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