Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of L-carnitine (0.5-2.0 mM) on the rates of alpha-decarboxylation of 1-14C-labeled branched-chain amino acids by gastrocnemius muscle and liver homogenates of fed rats was investigated. Carnitine increased the rate of alpha-decarboxylation of leucine (125%) and valine (28%) by muscle, but it was without effect on the oxidation of these amino acids by liver. Carnitine increased the rate of alpha-decarboxylation of alpha-ketoisocaproate by both tissues. This effect was more pronounced in muscle (130% increase) than in liver (41% increase). The activity of carnitine acyltransferase, with isovaleryl-CoA as a substrate, was 18 times higher in muscle mitochondria than in liver mitochondria. Both starvation and diabetes increased the rate of alpha-decarboxylation of leucine by muscle without having a remarkable effect on the concentration of carnitine or the activity of carnitine acyltransferase. We conclude that: a) carnitine stimulates decarboxylation of branched-chain amino acids by increasing the conversion of their ketoanalogues into carnitine esters, b) a greater carnitine acyltransferase activity in muscle than in liver may be responsible for the greater carnitine effect in muscle, c) carnitine does not appear responsible for the enhancement of leucine oxidation by muscle of starved and diabetic rats.
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PMID:Effect of carnitine on branched-chain amino acid oxidation by liver and skeletal muscle. 64 1

Diabetes, starvation and various hormonal treatments are known to alter drastically carnitine concentrations in the body. Before the mechanisms controlling carnitine metabolism could be determined, it was necessary to establish normal carnitine concentrations in both sexes at different ages. Carnitine was assayed in plasma, liver, heart and skeletal muscle of rats from birth to weaning. The plasma carnitine increased rapidly during the first 2 days after birth. Carnitine in both heart and skeletal muscle increased, whereas liver concentrations declined during the first week of life. A carnitine-free diet containing sufficient precursors for carnitine biosynthesis was fed to weanling rats. Groups of ten male and ten female rats were killed each week for 10 consecutive weeks. Carnitine was determined in plasma, liver, heart, skeletal muscle, urine and epididymis in the male. There was no difference in carnitine concentrations between the sexes at weaning. Plasma, heart and muscle concentrations were higher in adult male rats than in adult females. However, liver carnitine and urinary carnitine concentrations were higher in adult female than in adult male rats. The epididymal carnitine concentration increased very rapidly during 50 to 70 days of age and the differences in carnitine concentrations between the sexes also became apparent during this time. Thus both the age and the sex of the human subject or experimental animal must be considered when investigating carnitine metabolism.
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PMID:Variation in tissue carnitine concentrations with age and sex in the rat. 74 45

Carnitine is synthesized from lysine and methionine. In the rat, inadequate intake of either of these essential amino acids causes carnitine depletion. Inasmuch as protein deficiency is common in the hospital population, we have investigated the possible occurrence of nosocomial carnitine deficiency. Fasting serum carnitine concentration was measured in 16 normal and 247 patients in 16 disease groups. Normal range of carnitine was 55-103 muM. Only the cirrhotic group showed significant (P < 0.05) hypocarnitinemia. 14 of 36 hospitalized cirrhotics had subnormal values for serum carnitine. The creatinine/height index, midarm muscle circumference, and triceps skin-fold thickness indicated protein-calorie starvation in the 14 hypocarnitinemic liver patients. In six of the hypocarnitinemic cirrhotics (average serum level 50% of normal), spontaneous dietary intakes of carnitine, lysine, and methionine were measured and found to be only 5-15% as great as in six normocarnitinemic, healthy controls. When these six cirrhotic and six normal subjects were given the same lysine-rich, methionine-rich, and carnitine-free nutritional intake, the normals maintained normal serum carnitine levels and excreted 100 mumol/day, whereas the cirrhotics' serum level fell to 25% of normal, and urinary excretion declined to 15 mumol/day. Seven hypocarnitinemic cirrhotics died. Postmortem concentrations of carnitine in liver, muscle, heart, kidney, and brain averaged only one-fourth to one-third those in corresponding tissues of eight normally nourished nonhepatic patients who died after an acute illness of a 1-3-day duration. THESE DATA SHOW THAT CARNITINE DEPLETION IS COMMON IN PATIENTS HOSPITALIZED FOR ADVANCED CIRRHOSIS, AND THAT IT RESULTS FROM THREE FACTORS: substandard intake of dietary carnitine; substandard intake of lysine and methionine, the precursors for endogenous carnitine synthesis; and loss of capacity to synthesize carnitine from lysine and methionine.
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PMID:Deficiency of carnitine in cachectic cirrhotic patients. 89 75

Carnitine palmitoyltransferase (CPT total) activity and synthesis increase in states where the insulin/glucagon ratio is low, such as starvation and diabetes [Brady & Brady (1987) Biochem. J. 246, 641-646]. However, the effect of glucagon and insulin on CPT synthesis is unknown. The present experiments were designed to determine the effect of glucagon, cAMP [8-(chlorophenylthio) cyclic AMP], and insulin + cAMP on CPT transcription and mRNA amounts over time after injection. The CPT protein that was purified, used to generate antibody, and cloned in these studies was the 68 kDa mitochondrial protein described previously [Brady & Brady (1987) Biochem. J. 246, 641-646; Brady, Feng & Brady (1988) J. Nutr. 118, 1128-1136; Brady & Brady (1989) Diabetes 38, in the press]. Saline-injected control rats exhibited a 2-fold increase in hepatic CPT transcription rate and CPT mRNA over the 5 h experiment from 09:00 to 14:00 h. The effect was most probably due to the fasting state of the rats during the day. Glucagon injection caused an 8-fold increase in transcription rate by 90 min and a 4-fold increase in CPT mRNA by 90-120 min. The cAMP effect had reached a peak by the first time point taken (15 min). Transcription rate was increased 4-fold and CPT mRNA was increased 3-fold at this time. The combination of cAMP + insulin injection did not produce any significant increase in transcription rate or CPT mRNA over the saline-injected controls. CPT mRNA and transcription rate showed a clear dose-response to glucagon injection from 0 to 150 micrograms/100 g body wt. Total CPT activity and immunoreactive CPT were not increased during these experiments. The data indicate that glucagon and insulin interact in control of transcription rate and amount of CPT mRNA, but that increases in CPT immunoreactive protein and activity are temporally delayed. This lag probably relates to the half-life of the CPT protein in vivo, which has been estimated as 2-7 days.
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PMID:Regulation of carnitine palmitoyltransferase in vivo by glucagon and insulin. 254 60

The effects of carnitine and cobamamide were studied at the unspecific stage of anorexia nervosa treatment. Carnitine and cobamamide accelerated the amelioration of the patients' somatic state (body weight gain, gastrointestinal functions normalization). Experimental psychological technique of involved deciphering discovered that latent fatigue disappeared and mental performance sharply increased under carnitine and cobamamide treatment. Experimental model of anorexia nervosa was used for electron microscopy and morphometry of neocortical tissue structure after starvation period and in feeding rehabilitation with carnitine and cobamamide. These drugs were shown to promote cerebral mass growth, increase in neocortical layers thickness, pyramidal neurons volume, that led to full restoration of normal structure of neocortex. The data provide a basis suitable to recommend carnitineand cobamamide to treat patients with relevant anorexia.
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PMID:[Clinico-experimental substantiation of the use of carnitine and cobalamin in the treatment of anorexia nervosa]. 272 26

During starvation, a series of changes in whole body fuel use occur that result in conservation of fuel, particularly protein. Use of fat stores for ketone production and direct oxidation of fat as a primary fuel are characteristic of starvation. However, the mechanism by which this change develops is unclear. Carnitine is an important compound in the control of fat metabolism, since long-chain free fatty acids must be coupled with it to cross the mitochondrial membrane. This study attempts to define, in the fasting dog model, the interaction between plasma and muscle carnitine, its acyl esters, and the energy substrates available. Eight adult beagle dogs were studied during an 8-day period of starvation. Muscle and plasma were analyzed for free carnitine (FC), acid-soluble fraction, and long-chain esters (LCE), as well as substrate hormone profiles. Total carnitine (TC) and short-chain esters (SCE) were calculated. Muscle was analyzed for carnitine palmityl transferase activity (CPT). These measurements were performed on days 3, 5, and 8. There was a significant (p less than 0.05) loss in weight on days 3, 5, and 8. TC and FC increased significantly (p less 0.05) only on day 8; this occurred simultaneously with a significant (p less than 0.05) decrease in CPT. It was preceded by a significant (p less than 0.05) and persistent increase in plasma TC, FC, and LCE that developed on day 3. During starvation there was an increase in plasma carnitine levels before changes in muscle. The increase in muscle carnitine occurred between days 5 and 8 of starvation and seemed to be associated with a fall in CPT. This may be responsible either for or secondary to the decrease in metabolic rate that occurs during prolonged starvation.
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PMID:Carnitine metabolism during fasting in dogs. 352 Sep 14

The effects of riboflavin deficiency on mitochondrial and peroxisomal substrate oxidation were examined in young (treatment begun at weaning) and adult Sprague-Dawley rats that were fed diets low and high in fat. State 3 respiration rates (ADP-stimulated) were used as an estimate of mitochondrial oxidation rates. The oxidation of palmitoyl-CoA and palmitoylcarnitine, and to a lesser extent, glutamate, pyruvate and succinate, by hepatic mitochondria isolated from the young rats was depressed with riboflavin deficiency. There was no effect of dietary fat level on mitochondrial substrate oxidation. Carnitine palmitoyltransferase-A (CPT-A) Vmax was increased with riboflavin deficiency and with increasing dietary fat. Cyanide-insensitive palmitoyl-CoA oxidation was used to estimate peroxisomal palmitate oxidation. Expressed as total hepatic capacity, peroxisomal palmitate oxidation was depressed with riboflavin deficiency. This effect was the result of the reduced feed intake rather than riboflavin deficiency per se. Increasing dietary fat resulted in increased peroxisomal palmitate oxidation. Starvation of young rats did not change mitochondrial oxidation rates, although riboflavin-deficient starved rats exhibited increased rates of palmitoyl-CoA oxidation as well as increased CPT-A Vmax. In adult rats, after 5 wk of deficiency, only palmitoyl-CoA and palmitoylcarnitine oxidation rates were depressed. Dietary fat level did not interact with riboflavin deficiency. However, CPT-A Vmax was increased with riboflavin deficiency and with increased dietary fat level. Further, depressed hepatic fatty acid oxidation can occur in adult rats as a sequel to the feeding of riboflavin-deficient diets.
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PMID:Hepatic mitochondrial and peroxisomal oxidative capacity in riboflavin deficiency: effect of age, dietary fat and starvation in rats. 377 26

Methylglyoxal bis(guanylhydrazone) (MGBG) is an antileukemic agent and a structural polyamine analogue which inhibits S-adenosyl methionine decarboxylase. However, MGBG also produces profound mitochondrial structural damage and inhibition of fatty acid oxidation. Carnitine palmitoyltransferase-A (CPT-A) is located on the outer surface of the inner mitochondrial membrane and is the putative rate-controlling enzyme for mitochondrial long-chain fatty acid oxidation. The present experiments were designed to determine if MGBG inhibits CPT-A. Liver, heart and skeletal muscle mitochondria were isolated from rats following 24 hr of starvation. Measuring the reaction in the direction of palmitoylcarnitine plus CoA formation from palmitoyl-CoA plus carnitine ("forward reaction"), MGBG was competitive with l-carnitine. The MGBG CPT-A Ki values were (mM): liver, 5.0 +/- 0.6 (N = 15); heart 3.2 +/- 1.2 (N = 3); and skeletal muscle, 2.8 +/- 1.0 (N = 3). Lysis of hepatic mitochondria with Triton X-100 yielded a Ki of 4.0 +/- 2.0, which was not significantly different from intact mitochondria or inverted vesicles (4.9 mM). Purified hepatic CPT had a Ki of 4.2 mM. MGBG did not inhibit purified CPT in the "reverse reaction" (palmitoyl-CoA plus carnitine formation from palmitoylcarnitine plus CoA). Spermine and spermidine, which are structurally similar to MGBG, did not inhibit either CPT activity or acid-soluble product formation from 1-[14C]palmitoyl-CoA. MGBG inhibited mitochondrial state 3 oxidation rates of palmitoyl-CoA and palmitoylcarnitine, as well as of glutamate. However, the fatty acid substrates were considerably more sensitive than glutamate to MGBG inhibition. MGBG also increased hepatic mitochondrial aggregation which was reversed by l-carnitine. Fluorescence polarization, using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe, indicated that MGBG increased membrane rigidity in a dose-dependent manner. This effect was not altered by l-carnitine. MGBG also inhibited purified pigeon breast carnitine acetyltransferase (CAT; Ki = 1.6 mM). While MGBG appeared to be competitive with l-carnitine for both CPT and CAT, MGBG also exhibits a number of effects which may be mediated through membrane interaction and which are not reversed by carnitine.
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PMID:Effect of methylglyoxal bis(guanylhydrazone) on hepatic, heart and skeletal muscle mitochondrial carnitine palmitoyltransferase and beta-oxidation of fatty acids. 382 37

Carnitine metabolism during starvation was studied in adult lean and obese female Zucker rats. Comparisons were made between rats starved for 0, 3, 6 or 9 d. Total plasma carnitine was not affected by obesity or starvation, but free plasma carnitine decreased with starvation. Plasma acid-soluble acylcarnitine was lower in obese than in lean rats, and increased with starvation in both lean and obese rats. Plasma acid-insoluble acylcarnitine was not affected by obesity but increased with starvation. Liver free and acid-soluble acylcarnitine were lower in obese rats than lean rats, and starvation increased liver free carnitine and acid-insoluble acylcarnitine. Free carnitine was lower in muscle from obese rats than from lean rats. In kidney, free carnitine decreased during starvation. Heart carnitine was not affected by obesity or starvation. Urinary free carnitine and acid-soluble acylcarnitine clearance decreased during starvation. These studies indicate that: 1) lean and obese Zucker rats conserve carnitine during starvation; and 2) the decreases in liver carnitine concentration reflect the loss of cellular constituents rather than increases in total hepatic carnitine.
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PMID:Carnitine metabolism in lean and obese Zucker rats during starvation. 395 11

Carnitine palmitoyltransferase and carnitine octanoyltransferase activities in brain mitochondrial fractions were approx. 3-4-fold lower than activities in liver. Estimated Km values of CPT1 and CPT2 (the overt and latent forms respectively of carnitine palmitoyltransferase) for L-carnitine were 80 microM and 326 microM, respectively, and K0.5 values for palmitoyl-CoA were 18.5 microM and 12 microM respectively. CPT1 activity was strongly inhibited by malonyl-CoA, with I50 values (concn. giving 50% of maximum inhibition) of approx. 1.5 microM. In the absence of other ligands, [2-14C]malonyl-CoA bound to intact brain mitochondria in a manner consistent with the presence of two independent classes of binding sites. Estimated values for KD(1), KD(2), N1 and N2 were 18 nM, 27 microM, 1.3 pmol/mg of protein and 168 pmol/mg of protein respectively. Neither CPT1 activity, nor its sensitivity towards malonyl-CoA, was affected by 72 h starvation. Rates of oxidation of palmitoyl-CoA (in the presence of L-carnitine) or of palmitoylcarnitine by non-synaptic mitochondria were extremely low, indicating that neither CPT1 nor CPT2 was likely to be rate-limiting for beta-oxidation in brain. CPT1 activity relative to mitochondrial protein increased slightly from birth to weaning (20 days) and thereafter decreased by approx. 50%.
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PMID:Carnitine acyltransferase activities in rat brain mitochondria. Bimodal distribution, kinetic constants, regulation by malonyl-CoA and developmental pattern. 397 77


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