Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sarcomeric myosin heavy chain (MHC), the main component of the sarcomere, contains the ATPase activity that generates the contractile force of cardiac and skeletal muscles. The different MHC isoforms are encoded by a closely related multigene family. Most members (seven) of this gene family have been isolated and characterized in the rat, including the alpha- and beta-cardiac, skeletal embryonic, neonatal, fast IIA, fast IIB, and extraocular specific MHC. The slow type I skeletal MHC is encoded by the same gene that codes for the cardiac beta-MHC. Each MHC gene studied displays a pattern of expression that is tissue and developmental stage specific, both in cardiac and skeletal muscles. Furthermore, more than one MHC gene is expressed in each muscle while each gene is expressed in more than one tissue. The expression of each MHC gene in cardiac and skeletal muscles is modulated by thyroid hormone. Surprisingly, however, the same MHC gene can be regulated by the hormone in a significantly different manner, even in opposite directions, depending on the muscle in which it is expressed. Moreover, the skeletal embryonic and neonatal MHC genes, so far considered specific to these 2 developmental stages, are normally expressed in certain adult muscles and can be reinduced by hypothyroidism in specific muscles. This complex pattern of expression and regulation of the MHC gene family in cardiac and skeletal muscle sheds new light on the mechanisms involved in determining the biochemical basis of the contractile state. It also indicates that the cardiac contractile system needs to be examined in a broader context, including skeletal muscles, in order to understand fully its developmental and physiologic regulation.
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PMID:Developmental and hormonal regulation of sarcomeric myosin heavy chain gene family. 359 53

In earlier studies using papillary muscles of the rat left ventricle and highly sensitive thermopiles we demonstrated that the heat liberated per gram of myocardium per unit of developed tension-time integral is decreased when the rats suffered from hypothyroidism or renal hypertension. This increase in economy of force production was shown to be associated with a decrease in myosin-ATPase activity and a change in isomyosin composition. In a recent study we showed an increase in heat per gram of mammalian myocardium per tension-time integral of 70% after application of isoproterenol. In order to study the relationship between energy costs and developed tension-time integral in the human heart, haemodynamics and myocardial oxygen consumption were measured. The data were obtained using a Millar microtip catheter pressure transducer and the argon method. Haemodynamics and myocardial energetics were analysed in 8 patients without significant heart disease before and after application of isoproterenol and in 10 patients with dilative cardiomyopathy (NYHA II-III). During one cardiac cycle, myocardial oxygen consumption per gram of LV myocardium per beat (MVO2/g x beat) is related to LV stress-time integral (integral of sigma xt). The economy of myocardial contraction (EC) was calculated by (formula; see text) EC was 11.3 +/- 3.2 in normal and 14.3 +/- 4.7 dyn x s x g/cm2 x mu cal in dilative cardiomyopathic hearts (NS). Isoproterenol decreased EC from 11.3 +/- 3.2 to 5.5 +/- 1.6 dyn x s x g/cm2 x mu cal in the normal hearts (p less than 0.01). In the rat myocardium, changes in economy of force generation were found due to catecholamines, pressure overload and hypothyroidism. In the human heart, similar energetic changes were observed due to catecholamines. No significant differences in energy of force production were seen between normal and dilative cardiomyopathic hearts. The effect of catecholamines in the mammalian and human myocardium is explained by changes in activation processes and in chemomechanical energy transduction at the level of the contractile proteins.
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PMID:Acute and chronic changes of myocardial energetics in the mammalian and human heart. 366 28

The receptor for cardiac glycosides probably is identical with the (Na+ + K+)-ATPase (approximately 250 000 Daltons). Its affinity for the therapeutically used glycosides is extremely different in different species (KD approximately 10(-9)M (human heart) - approximately 10(-7)M (rat heart]. In the latter, two distinct receptor types have been demonstrated (high- and low-affinity receptors) with different effects. In the human heart, there may be two cardiac glycoside receptors as well, although this has not been proved as yet. The number of cardiac glycoside receptors and their affinity is regulated in certain states and diseases. An increased receptor density is found in hyperthyroid states, in chronic hypokalaemia and in chronic digitalis treatment. A decreased number is measured in ischemic heart disease, in dilated cardiomyopathy and in hypothyroidism. Parallel to the decreased receptor density the maximal cardiac glycoside induced positive inotropy is reduced. Pronounced toxicity occurs, if the digitalis dose is increased in spite of missing effects.
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PMID:[Changes of affinity and capacity of cardiac glycoside receptors]. 391 28

We have analyzed the effect of 6-propylthiouracil-induced hypothyroidism on neonatal fiber type differentiation in the rat soleus muscle. Body weight, total soleus fiber number, histochemical fiber type differentiation, and morphometry were determined at 7, 14, 21, and 28 days. Neonatal hypothyroidism (1) inhibits the apparent approximately 50% increase in soleus muscle fiber number occurring at 14-21 days, (2) blocks the transformation of type 2C to type 2A fibers occurring between 14 and 21 days, (3) preferentially inhibits the increase in type 2 fiber diameter, and (4) retards the development of sarcoplasmic reticulum. Immature muscle fibers reveal type 1 and type 2 fiber myosin adenosine triphosphatase (ATPase) differentiation at pH 10.3, which drops to pH 9.4 with maturation. No myosin ATPase differentiation was found at pH 9.4 in the hypothyroid animals, even at 28 days.
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PMID:Postnatal histochemical fiber type differentiation in normal and hypothyroid rat soleus muscle. 405 73

The rate of calcium transport by isolated sarcoplasmic reticulum from rat skeletal muscle increases markedly during the first 4 wk of life and thereafter remains relatively constant. When animals are made hypothyroid during the first 3 wk of life, there is a marked inhibition of the increase in calcium transport by the sarcoplasmic reticulum. Production of hypothyroidism after 4 wk of age, at which time the calcium transport by sarcoplasmic reticulum has reached maximum levels, results in a depression in the rate of calcium transport. There is no clear alteration in ATPase activity of the sarcoplasmic reticulum to account for the low calcium transport in hypothyroidism. It is proposed that the decrease in calcium transport by sarcoplasmic reticulum may account for observed alterations in the intrinsic contractile properties of muscle in the hypothyroid animal.
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PMID:Calcium transport by skeletal muscle sarcoplasmic reticulum in the hypothyroid rat. 423 81

1. Cardiac sarcoplasmic reticulum (SR) was prepared by differential centrifugation from euthyroid, hyperthyroid, hypothyroid as well as (131)I-treated plus thyroxine-substituted rabbits. The function of the isolated SR has been characterized by measuring the ATP-dependent calcium uptake, the calcium storing capacity, the calcium concentrating ability and the calcium-dependent ATP hydrolysis by the calcium-activated ATPase in the presence of oxalate.2. The rate of calcium uptake and the rate of the calcium-dependent ATP hydrolysis (calcium-activated ATPase) by the SR were significantly increased in hyperthyroidism, whilst both activities were markedly reduced in hypothyroidism. Thyroxine administration to (131)I-treated animals prevented a decrease in the rate of calcium uptake as well as in the rate of the calcium-dependent ATP hydrolysis by the calcium-activated ATPase.3. The transport ratio (rate of calcium uptake divided by the rate of calcium-dependent ATP hydrolysis) of SR preparations from euthyroid controls was 0.93, suggesting a stoicheiometry of calcium uptake and calcium-activated ATP split of 1.0. The transport ratio was unchanged in one hyper- and hypothyroid group, whilst a small but significant decrease or increase was observed after an excessive thyroxine treatment of a prolonged state of hypothyroidism, respectively.4. The saturation kinetics of calcium transport by the SR were described by Michaelis-Menten kinetics. The maximum rate of calcium uptake (V) was 0.193+/-0.004, 0.223+/-0.002 and 0.124+/-0.003 mumole Ca(2+)/mg protein. min (means +/-S.E.) for euthyroid, hyperthyroid and hypothyroid SR, respectively. The Michaelis constants (K(m)) were (2.87+/-0.30) x 10(-7)M (2.68+/-0.15) x 10(-7)M and (4.00+/-0.48) x 10(-7)M for the euthyroid, hyperthyroid and hypothyroid SR, respectively (means +/-S.E.). The K(m) values for the hyper- and hypothyroid SR were not significantly different from controls.5. The calcium storing capacity as well as the calcium concentrating ability of the SR was unaltered at different levels of thyroid activity.6. The steady-state level of calcium was the same for SR isolated from euthyroid, hyperthyroid and hypothyroid rabbits, indicating that calcium influx and calcium efflux are strongly coupled at steady-state filling of the SR.7. It is suggested that the increased or reduced rate of calcium transport by the SR in hyperthyroidism or hypothyroidism, respectively, found in vitro, might be at least partially responsible for the shortening of the relaxation time of cardiac muscle in the hyperthyroid state and the prolongation of the relaxation time in the hypothyroid state observed in vitro and in vivo.
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PMID:The calcium pump of cardiac sarcoplasmic reticulum. Functional alterations at different levels of thyroid state in rabbits. 426 11

The relationship between net tubular reabsorption of sodium and renal microsomal sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) was evaluated in hypothyroid and hyperthyroid rats and in age-matched euthyroid controls. Tubular sodium reabsorption per gram of kidney was lower in thyroidectomized rats than in controls (186+/-14 vs. 246+/-12 mueq/min; P < 0.005) and was accompanied by a quantitatively similar reduction in Na-K-ATPase specific activity (49.4+/-2.4 vs. 65.8+/-2.3 mumol inorganic phosphate (P(t))/mg protein per h; P < 0.001). This decrement was present in both cortex and outer medulla, and was limited to Na-K-ATPase since other representative enzymes not involved in sodium transport (magnesium-dependent adenosine triphosphatase [Mg-ATPase], glucose-6-phosphatase, 5'-nucleotidase) remained unchanged or increased in the hypothyroid animals. Conversely, Na-K-ATPase rose when sodium reabsorption increased in euthyroid rats treated with triiodothyronine. Subsequent experiments were performed to determine to what extent the decrease in Na-K-ATPase is due to lack of thyroid hormone per se or to an adaptive response to decreased reabsorptive sodium load. Triiodothyronine in concentrations of 10(-12) to 10(-5) M had no effect in vitro on microsomal Na-K-ATPase of either thyroidectomized or euthyroid rats. When hypothyroid rats were uninephrectomized or treated with methylprednisolone, sodium reabsorption per gram kidney increased markedly and was similar to that of intact controls. Despite persistence of the hypothyroid state, Na-K-ATPase specific activity also increased to levels not significantly different from euthyroid animals. These data suggest that decreased tubular sodium transport is a major determinant of the reduction in renal Na-K-ATPase in thyroid deficiency since the latter can be reversed by increasing sodium reabsorption during continuing hypothyroidism. Furthermore, the modest sodium leak of hypothyroid animals does not appear to be due to decreased Na-K-ATPase since it was not corrected by uninephrectomy despite restoration of both cortical and medullary Na-K-ATPase activity to normal by this maneuver. The close correlation between net sodium reabsorption and Na-K-ATPase in all the experimental situations described here demonstrates that renal Na-K-ATPase changes adaptively in hyper- or hypothyroidism as it does in numerous situations in the normal animal, in accord with its postulated role in the active transport of sodium across the renal tubule.
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PMID:Renal sodium- and potassium-activated adenosine triphosphatase and sodium reabsorption in the hypothyroid rat. 434 43

Changes in contractility and synthesis of protein were studied in different types of muscles of hypo- and athyroid ratts during adaptation to physical exercise. Intensity of the exercises used corresponded to metabolic power output of 70% VO2max. Thyroidectomy caused a significant decrease in Mg2+ activated actomyosin ATPase activity and in content of RNA in myocardium and in fast oxidative-glycogenolytic and glycogenolytic skeletal muscle fibers. Exercises, intensity of which corresponded to metabolic power output of 70% VO2max led to a more distinct decrease in Mg2+ activated actomyosin ATPase activity in fast glycogenolytic muscle fibers, but in fast oxidative-glycogenolytic fibers the enzymatic activity was increased up to the level comparable with that of intact animals. Rhysical working capacity of athyroid rats was lower by 40% as compared with intact trained animals. Hypothyroidism, induced by means of administration of KJ into previously trained rats, caused a decrease in physical working capacity by 25%.
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PMID:[Adaptation of skeletal muscle and myocardium to increased motor activity in hypo- and athyroid rats]. 617 99

Recent studies have shown that approximately 75% of the nuclear 3,5,3'-triiodothyronine (T(3)) present in adult rat cerebral cortex (Cx) derives from 5'-deiodination of thyroxine (T(4)) within this tissue. The activity of iodothyronine 5'-deiodinase (I 5'D), the enzyme catalyzing T(4) to T(3) conversion, increases rapidly after thyroidectomy, suggesting that this could be a compensatory response to hypothyroxinemia. To evaluate this possibility during the period of central nervous system maturation, we studied several thyroid hormone-responsive enzymes (aspartic transaminase [AT], succinic dehydrogenase [S.D.], and Na/K ATPase) in the Cx of 2-, 3-, and 4-wk-old rats. The rats were made congenitally hypothyroid by placing 1, 2, 5, and 20 mg methimazole (MMI) in 100 ml of the mothers' drinking water from day 16 of gestation throughout the nursing period and to the litters after weaning. In addition, serum thyroid hormones, I 5'D, and, in some experiments, in vivo T(4) to T(3) conversion in Cx were measured in the same pups. Serum T(4) concentrations varied from <1 to 40 ng/ml and were generally inversely related to maternal MMI dose. Serum T(3) was less affected by MMI than was T(4). At 2 wk, decreases in AT, S.D., and ATPase were present in the 20-mg-MMI group but not in the 5-mg-MMI pups despite low serum T(4) (<10 ng/ml) in the latter. At 3 and 4 wk, both 5- and 20-mg-MMI groups had significant reductions in these cortical enzymes despite a normal serum T(3) in the 5-mg-MMI rats. Cortical I 5'D activity was 10-fold the control value in 5- and 20-mg-MMI animals at 2 wk but increased only three- to fivefold at 3 and 4 wk. I 5'D correlated inversely with serum T(4) (r >/= 0.96) at all ages, but the less marked elevation of this enzyme in 3- and 4-wk-old pups was not accompanied by an increase in serum T(4). Serum T(3) increased or remained the same between 2 and 3 wk. These results suggested that the 10-fold increase in I 5'D at 2 wk protected the 5-mg-MMI group from tissue hypothyroidism, but that the three- to fivefold increase at 3 and 4 wk could not. Injection of approximately 250 ng T(4)/100 g body weight to 2-wk-old, 20-mg-MMI pups (one-sixth the normal T(4) production rate) led to both a 1.8-ng/g cortical tissue increment in cortical T(3) and a significant increase in AT at 24 h, compared with a 0.38-ng/g cortical tissue T(3) increment and no change in AT in euthyroid controls. The larger increment in T(3) of the 20-mg-MMI pups was due in great part to increased fractional T(4) to T(3) conversion. Although the latter resulted in greater serum T(3) concentrations, three-fourths of the newly formed T(3) in the cortex was generated in situ, and it was blocked by iopanoic acid as was the increase in AT. We conclude that 70-80% of the T(3) in the Cx of the neonatal rat is produced locally. Serum T(4) appears to serve both as a precursor for T(3) and as a critical signal for increases in cortical I 5'D. The increased I 5'D can result in normal or near-normal cerebrocortical T(3) concentrations despite marked reductions in serum T(4). This mechanism seems to be particularly effective around 2 wk of age when many thyroid-hormone-dependent maturational changes occur in the rat Cx.
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PMID:Comparison of iodothyronine 5'-deiodinase and other thyroid-hormone-dependent enzyme activities in the cerebral cortex of hypothyroid neonatal rat. Evidence for adaptation to hypothyroidism. 621 29

The metabolic and contractile activity of muscle was determined in immature cockerels made hypothyroid by surgical thyroidectomy at 6 weeks of age. Four weeks after thyroidectomy the activity of Mg2+-activated myofibrillar ATPase and total phosphorylase was reduced in the fast-phasic, posterior latissimus dorsi (PLD) and scapulotriceps (ST) muscles. The activities of these enzymes were unaffected in the slow-tonic, anterior latissimus dorsi (ALD) muscle. Thyroidectomy had no effect on length of the muscles studied but reduced the weight of the ALD and ST muscles. These results suggest that hypothyroidism results in a "slowing down" of fast-phasic muscles, although it does not affect the activity of slow-tonic muscles.
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PMID:Muscle development in thyroidectomised chickens (Gallus domesticus). 623 24


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