Metabolism of formaldehyde in vivo

Abstract

Age-related cognitive impairment is regarded as a chronic progression of dysfunction and loss of neurons, accompanied with formation of senile plaque (ß-amyloid deposition) and neurofibrillary tangles (paired helical filaments of hyperphosphorylated Tau). Approximately 40% of the cases are suffered from endogenous formaldehyde accumulation. Dysmetabolism of formaldehyde shows a positive relationship with Alzheimer's disease (AD) for about 40% of AD patients who have high levels of urine formaldehyde (see Chap. 8 Cognitive Impairment). To have a convenient and clear explanation, we would like to divide the cellular formaldehyde pathways into two parts: "formaldehyde coming (synthesis or production)" and "formaldehyde going (process or degradation)". The metabolic homeostasis of formaldehyde is maintained between the "coming" and "going" pathways under the physiological state. In fact, formaldehyde comes from multiple pathways related with many compounds such as sugars, lipids, proteins, and nucleic acids, as well as some small molecules and goes away in a relatively narrow lane; besides, it also goes to participate in the other pathways, for instance, as donor to modify histones and DNA. Either "coming" or "going" metabolism dysfunctions would lead to increase or decrease of endogenous formaldehyde. As described in Chap. 8, imbalance (lack or excess) of formaldehyde metabolism induces decline of learning and memory for drosophila and rodents. It has been known that intestinal microbiota is involved in the metabolism of endogenous formaldehyde, and we discuss this topic in details in Chap. 6. In this chapter, we discuss the characteristics of the endogenous formaldehyde metabolism and summarize the pathways, which are responsible for the generation and clearance of endogenous formaldehyde.