Lecithin-cholesterol acyltransferase (LCAT) catalyzes the formation of cholesterol esters on high density lipoproteins (HDL) and plays a critical role in reverse cholesterol transport. Sphingomyelin, an important constituent of HDL, may regulate the activity of LCAT at any of the key steps of the enzymatic reaction: binding of LCAT to the interface, activation by apo A-I, or inhibition at the catalytic site. In order to clarify the role of sphingomyelin in the regulation of the LCAT reaction and its effects on the structure of apolipoprotein A-I, we prepared reconstituted HDL (rHDL) containing egg phosphatidylcholine, cholesterol, apolipoprotein A-I, and up to 22 mol % sphingomyelin. Because the interfacial properties of substrate particles can dramatically affect LCAT binding and kinetics, we also prepared and analyzed proteoliposome substrates having the same components as the rHDL, except for a 4-fold higher ratio of phospholipid to apolipoprotein A-I. The reaction kinetics of LCAT with the rHDL particles revealed no significant change in the apparent V max but showed a concentration-dependent increase in slope of the reciprocal plots and in the apparent K m values with sphingomyelin content. The dissociation constant (K d ) for LCAT with these particles increased linearly with sphingomyelin content up to 22 mol %, changing in parallel with the apparent K m values. No structural changes of apolipoprotein A-I were detected in the particles with increasing content of sphingomyelin, but fluorescence results with lipophilic probes revealed that significant changes in the acyl chain, backbone, and head group regions of the lipid bilayer of the particles are introduced by the addition of sphingomyelin. On the other hand, the proteoliposome substrates also had increased K d values for LCAT at high sphingomyelin contents but compared with the rHDL particles had a 6 -10-fold lower affinity for LCAT binding and exhibited kinetics consistent with competitive inhibition by sphingomyelin at the active site. These results show conclusively that the dominant mechanism for the inhibition of LCAT activity with rHDL particles by sphingomyelin is the impaired binding of the enzyme to the interface. The results also underscore the significant differences in the enzyme reaction kinetics with different substrate particles. Lecithin-cholesterol acyltransferase (LCAT)1 plays a critical role in the maintenance of cholesterol homeostasis. LCAT participates in the reverse cholesterol transport pathway, maintaining a gradient for the diffusion of free cholesterol from peripheral tissues into high density lipoproteins (HDL) by catalyzing cholesterol ester (CE) formation from HDL surface phosphatidylcholine (PC) and cholesterol. As a result of LCAT activity, cholesterol is removed from peripheral cell membranes and, as CE, is ultimately removed and metabolized by the liver.Several factors contribute to the maintenance of cellular cholesterol homeostasis, including the activity of HMG-CoA reductase and acyl-CoA acyltransferase, which are r...
Objective: To present athletic trainers with recommendations for the content and administration of the preparticipation physical examination (PPE) as well as considerations for determining safe participation in sports and identifying disqualifying conditions.Background: Preparticipation physical examinations have been used routinely for nearly 40 years. However, considerable debate exists as to their efficacy due to the lack of standardization in the process and the lack of conformity in the information that is gathered. With the continuing rise in sports participation at all levels and the growing number of reported cases of sudden death in organized athletics, the sports medicine community should consider adopting a standardized process for conducting the PPE to protect all parties.Recommendations: Recommendations are provided to equip the sports medicine community with the tools necessary to conduct the PPE as effectively and efficiently as possible using available scientific evidence and best practices. In addition, the recommendations will help clinicians identify those conditions that may threaten the health and safety of participants in organized sports, may require further evaluation and intervention, or may result in potential disqualification.
Sleep deprivation is very common among collegiate student athletes, resulting in impacts on mood, physiology, and performance. There are multifactorial contributions to sleep deprivation, but resulting alterations in sleep architecture explain impacts on learning, vigilance, mood, and athletic performance. Recognition of the physical impacts is key. Clinical inquiry is warranted. Medication can be helpful short term but should be used with caution due to effects on sleep cycle and the potential for addiction. Education is an effective intervention to increase sleep time, improve mood, and improve long-term sleep habits. Sleep extension, particularly in the setting of chronic partial sleep deprivation improves mood, vigilance, and athletic performance in the college setting.
Some 30 million Americans are involved in equestrian sports. Although there is significant literature regarding catastrophic injury, there is very little literature that addresses overuse injury and its effect on rider and horse. As the horse and rider function as a unit, overuse injuries to the rider can affect the horse's training and responsiveness. Sports physicians treating riders should understand correct posture in the saddle and its alteration by muscular imbalance and injury. This review discusses common equestrian events, and common overuse injuries in recreational and competitive riders.
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