Abstract
Citrate is an intermediate in the “Tricarboxylic Acid Cycle” and is used by all aerobic organisms to produce usable chemical energy. It is a derivative of citric acid, a weak organic acid which can be introduced with diet since it naturally exists in a variety of fruits and vegetables, and can be consumed as a dietary supplement. The close association between this compound and bone was pointed out for the first time by Dickens in 1941, who showed that approximately 90% of the citrate bulk of the human body resides in mineralised tissues. Since then, the number of published articles has increased exponentially, and considerable progress in understanding how citrate is involved in bone metabolism has been made. This review summarises current knowledge regarding the role of citrate in the pathophysiology and medical management of bone disorders.
Highlights
Citrate is an intermediate in the tricarboxylic acid cycle (TCA cycle, Krebs cycle), a central metabolic pathway for all aerobic organisms, including animals, plants, and bacteria [1,2]
The number of published articles dealing with this topic has increased exponentially (Figure 1), and considerable progress in understanding how citrate is involved in bone metabolism has been made
In response to the elevated acid load occurring in metabolic acidosis, there is a notable increase in citrate recovery with subsequent hypocitraturia; urinary citrate excretion may be used as a laboratory parameter for monitoring the diet- and metabolism-dependent systemic acid-base status, even in subjects without overt metabolic acidosis [29,35,36]
Summary
Citrate is an intermediate in the tricarboxylic acid cycle (TCA cycle, Krebs cycle), a central metabolic pathway for all aerobic organisms, including animals, plants, and bacteria [1,2]. When the cellular ATP is abundant and the energy demand of the cells is low, the excess citrate can be exported to the cytosol by means of a mitochondrial citrate carrier [3] It can be used for the lipid biosynthesis of highly proliferating cells [4] or for supporting the tissue-related functions of specialised cells, including the mineralisation of the extracellular matrix by osteoblasts, the bone-forming cells [5]. In this regard, the close association between citrate and bone was pointed out for the first time by Dickens in 1941 [6]. Are included with the exception of those dealing with citrate as an anticoagulant
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