The sarcoplasmic reticulum Ca 2؉ -ATPase transports Ca 2؉ using the chemical energy derived from ATP hydrolysis. Part of the chemical energy is used to translocate Ca 2؉ through the membrane (work) and part is dissipated as heat. The amount of heat produced during catalysis increases after formation of the Ca 2؉ gradient across the vesicle membrane. In the absence of gradient (leaky vesicles) the amount of heat produced/mol of ATP cleaved is half of that measured in the presence of the gradient. After formation of the gradient, part of the ATPase activity is not coupled to Ca 2؉ transport. We now show that NaF can impair the uncoupled ATPase activity with discrete effect on the ATPase activity coupled to Ca 2؉ transport. For the control vesicles not treated with NaF, after formation of the gradient only 20% of the ATP cleaved is coupled to Ca 2؉ transport, and the caloric yield of the total ATPase activity (coupled plus uncoupled) is 22.8 kcal released/mol of ATP cleaved. In contrast, the vesicles treated with NaF consume only the ATP needed to maintain the gradient, and the caloric yield of ATP hydrolysis is 3.1 kcal/mol of ATP. The slow ATPase activity measured in vesicles treated with NaF has the same Ca 2؉ dependence as the control vesicles. This demonstrates unambiguously that the uncoupled activity is an actual pathway of the Ca 2؉ -ATPase rather than a contaminating phosphatase. We conclude that when ATP hydrolysis occurs without coupled biological work most of the chemical energy is dissipated as heat. Thus, uncoupled ATPase activity appears to be the mechanistic feature underlying the ability of the Ca 2؉ -ATPase to modulated heat production.The main physiological role of the sarcoplasmic reticulum Ca 2ϩ -ATPase is to remove Ca 2ϩ from the cytosol thus controlling the transition between muscle contraction and relaxation (1-4). The ATPase uses the energy derived from ATP hydrolysis to transport Ca 2ϩ across the membrane thus converting chemical energy into osmotic energy. The catalytic cycle of the Ca 2ϩ -ATPase can be reversed, during which Ca 2ϩ leaves the vesicles through the ATPase, and coupled to the Ca 2ϩ efflux, ATP is synthesized from ADP and P i using the energy derived from the Ca 2ϩ gradient (3, 4 -9). Contrasting to the removal of Ca 2ϩ from the medium, there is no evidence indicating that the reversal of the Ca 2ϩ pump can play a role in muscle physiology. In recent years, two more properties of the Ca 2ϩ -ATPase were discovered that apparently are of no physiological relevance, the uncoupled Ca 2ϩ efflux (10 -12) and the uncoupled ATPase activity (13-15). During transport, part of the Ca 2ϩ accumulated by the vesicles leaks to the medium through the ATPase, but this efflux is not coupled to ATP synthesis. The uncoupled Ca 2ϩ -ATPase activity was described by Yu and Inesi (13), who observed that the progressive rise in the Ca 2ϩ concentration in the vesicle lumen promotes the hydrolysis of ATP without concomitant Ca 2ϩ translocation through the membrane. Depending on the conditions used, the...

This report measured the amount of heat released during Ca(2+) transport and ATP hydrolysis by vesicles derived from the sarcoplasmic reticulum of rabbit slow (SM) and fast (FM) muscle. During ATP hydrolysis, part of the chemical energy released is used to translocate Ca(2+) through the membrane (work) and part is dissipated as heat. The amount of heat produced during catalysis increases after formation of the Ca(2+) gradient across the vesicle membrane. In the absence of gradient (leaky vesicles), the heat produced per mol of ATP cleaved by SM and FM vesicles was the same and varied between 7.7-9.1 kcal. In the presence of the gradient the heat produced by SM and FM vesicles differed, 13.4 kcal/mol and 23.0 kcal/mol ATP cleaved, respectively. After formation of the gradient, part of the ATPase activity was not coupled to Ca(2+) transport. The difference of heat produced by FM and SM vesicles during ATP hydrolysis was related to the rate of uncoupled ATPase activity. When extended to the living cell, the data described indicate that the amount of heat produced by the Ca(2+)-ATPase of SM muscle is 36 times smaller than that produced by the FM. Thyroid hormone 3,5,3'-triiodo L-thyronine (T3) regulate both thermogenesis and the transcription of the sarcoplasmic reticulum Ca(2+)-ATPase isoforms found in SM and FM. The findings described in this report raise the possibility that one of the mechanisms of thermogenesis control may be related to the regulation of Ca(2+)-ATPase isoforms expression by T3.

SUMMARYACTH-dependent Cushing syndrome (CS) due to ectopic ACTH production is most times difficult to manage. The identification of the source of ACTH may take many years. Surgery or chemotherapy for the primary tumor is not always possible. Control of Cushing symptoms is many times achieved using medication, or bilateral adrenalectomy in refractory cases. This case presents a Brazilian male who showed severe hypertension, mood changes, muscle weakness, darkening of skin, and increased abdominal fat. An investigation for Cushing syndrome was carried out and, after a four-year follow-up, a carotid glomus tumor (chemodectoma) was confirmed, a rare ectopic ACTH-producing tumor. Besides, the patient presented cyclic Cushing syndrome that was exacerbated by diverticulitis episodes. This case presents interesting pitfalls on diagnosis and management of ACTH-dependent CS. This is the only report of a chemodectoma that produced ACTH in the literature. Arq Bras Endocrinol Metab. 2012;56(5):324-30 SUMÁRIO A síndrome de Cushing ACTH-dependente causada por produção ectópica de ACTH é, muitas vezes, difícil de diagnosticar e conduzir. A identificação da fonte produtora de ACTH pode demorar muitos anos. A cirurgia ou quimioterapia para o tumor primário nem sempre é possível, sendo o controle do hipercortisolismo alcançado com uso de fármacos ou adrenalectomia bilateral, nos casos refratários. Este caso apresenta um homem com hipertensão grave, mudança de humor, fraqueza proximal, escurecimento da pele e aumento de gordura abdominal. A investigação para síndrome de Cushing foi feita e, após quatro anos de acompanhamento, confirmou--se um tumor de glomus carotídeo (quemodectoma), causa rara de tumor secretor de ACTH. Nesse período, o paciente apresentou síndrome de Cushing cíclica, exacerbada por crises de diverticulite. O caso ilustra pontos importantes no diagnóstico, no acompanhamento e na condução da síndrome de Cushing ACTH-dependente, sendo este o único caso de tumor de glomus de carótida produzindo ACTH descrito na literatura médica. Arq Bras Endocrinol Metab. 2012;56(5):324-30

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Previous studies have reported allelic loss in chromosomal region 13q14 in pituitary tumors. However, the role of RB1 in this region has not been clarified. We performed a tumor deletion map of chromosomal region 13q14 with pituitary adenomas and matched blood samples of 43 patients with acromegaly. Twenty-one patients had non-invasive tumors, 19 had invasive tumors, and in 3 this information was not available. Results showed loss of heterozygosity in at least one microsatelite marker of region 13q14 in 12% (5 of 43) of the somatotropinomas. Retention of marker D13S1325, telomeric to RB1, suggests that the putative tumor suppressor gene is located centromeric to this region, which includes RB1 locus. The participation of RB1 was excluded in four of the five cases because retinoblastoma protein was shown to be positive in these tumors in our previous study. Allelic loss occurred in similar frequency in invasive and noninvasive adenomas. In summary, we confirmed the participation of chromosomal region 13q14 in a subset of GH-secreting adenomas with no regard to tumor grade. RB1 was not implicated, suggesting the participation of another tumor suppressor gene in this region during the first steps of somatotropinoma development.