Abstract:
In the breath research community\'s search for volatile organic compounds that can act as non-invasive biomarkers for various diseases, hundreds of endogenous volatiles have been discovered. Whilst these systemic chemicals result from normal and abnormal metabolic activities or pathological disorders, to date very few are of any use for the development of clinical breath tests that could be used for disease diagnosis or to monitor therapeutic treatments. The reasons for this lack of application are manifold and complex, and these complications either limit or ultimately inhibit the analytical application of endogenous volatiles for use in the medical sciences. One such complication is a lack of knowledge on the biological origins of the endogenous volatiles. A major exception to this is isoprene. Since 1984, i.e. for 40 years, it has been generally accepted that the pathway to the production of human isoprene, and hence the origin of isoprene in exhaled breath, is through cholesterol biosynthesis via the mevalonate (MVA) pathway within the liver. However, various studies between 2001 and 2012 provide compelling evidence that human isoprene is produced in skeletal muscle tissue. A recent multi-omic investigation of genes and metabolites has revealed that this proposal is correct by showing that human isoprene predominantly results from muscular lipolytic cholesterol metabolism. Despite the overwhelming proof for a muscular pathway to isoprene production in the human body, breath research papers still reference the hepatic MVA pathway. The major aim of this perspective is to review the evidence that leads to a correct interpretation for the origins of human isoprene, so that the major pathway to human isoprene production is understood and appropriately disseminated. This is important, because an accurate attribution to the endogenous origins of isoprene is needed if exhaled isoprene levels are to be correctly interpreted and for assessing isoprene as a clinical biomarker.
摘要:
在呼吸研究社区的搜索挥发性有机化合物,可以作为各种疾病的非侵入性生物标志物,已经发现了数百种内源性挥发物。虽然这些全身性化学物质是由正常和异常的代谢活动或病理障碍引起的,迄今为止,很少有用于开发可用于疾病诊断或监测治疗性治疗的临床呼气试验。这种缺乏应用的原因是多方面和复杂的,这些并发症限制或最终抑制了内源性挥发物在医学科学中的分析应用。一个这样的复杂因素是缺乏关于内源性挥发物的生物学起源的知识。对此的主要例外是异戊二烯。自1984年以来,即四十年来,人们普遍认为,生产人类异戊二烯的途径,因此,呼出气中异戊二烯的起源,是通过肝脏内的甲羟戊酸(MVA)途径进行胆固醇生物合成。然而,2001年至2012年之间的各种研究提供了令人信服的证据,表明人类异戊二烯是在骨骼肌组织中产生的。最近对基因和代谢产物的多项研究表明,该提议是正确的,因为表明人类异戊二烯主要来自肌肉脂肪分解胆固醇代谢。尽管有压倒性的证据证明人体内有肌肉途径产生异戊二烯,呼吸研究论文仍然引用肝MVA途径。这个观点的主要目的是审查导致对人类异戊二烯起源的正确解释的证据,以便了解和适当传播人类异戊二烯生产的主要途径。这很重要,因为如果要正确解释呼出的异戊二烯水平并评估异戊二烯作为临床生物标志物,则需要准确归因于异戊二烯的内源性起源。