Go Fly a Chitin The Mystery of Chitin and Chitinases in Vertebrate Tissues

Abstract

A controversy arose decades ago whether the DG42 gene product expressed during frog embryogenesis synthesized hyaluronan or chitin. Both sets of investigators were correct. It is now possible to understand how prescient those findings were. Synthesis of a seven to nine chitin sugar chain fragment is required before hyaluronan synthesis begins. Thus, DG42 indeed synthesizes both hyaluronan and chitin. Hyaluronan turns over rapidly in vertebrate tissues, but chitin oligomers are difficult to degrade. They accumulate and can cause pathology. Chitin is a simple beta-linked repeating sugar homopolymer found prominently in the building block structures of fungi, molluscs, arthropods, and other forms of invertebrate life. It is a highly resistant insoluble material requiring chitin synthases for production and chitinases for degradation. Mysteriously, chitins and chitinases also occur in vertebrate tissues, while it had previously been assumed that no chitins were contained therein. That assumption is now challenged based on recent biochemical evidence. Chitin does accumulate in many tissues, but may be particularly toxic to neurons. Its accumulation in the brain may account for the cognitive decline found in patients with Alzheimer's disease. The DG42 observations together with the participation of chitins and chitinases in several human diseases, among which in addition to Alzheimer's disease include Gaucher's disease, asthma, and aspects of abnormal immune recognition justify a reexamination of these topics. The purpose of this review is to summarize data in order to place chitins and their attendant enzymes in a rational framework in an attempt to create a cohesive story.

An Overview of the Protective Effects of Chitosan and Acetylated Chitosan Oligosaccharides against Neuronal Disorders

“…As one of the bioactive compounds derived from the sea, chitosan and its derivatives have been reported to have good neuroprotective properties, such as β-amyloid and acetylcholinesterase inhibitory activities, anti-neuroinflammation, and anti-apoptosis effects [8,23,24,25,26]. Moreover, the accumulation of chitin fragments may contribute to the dementia of Alzheimer’s disease and chitinase could possibly be used for the treatment of Alzheimer’s disease [89]. Herein, our review presents an overview of the recent progress in research on the neuroprotective effects and mechanisms of chitosan and its derivatives against different neuronal disorders.…”

Hyaluronan Mediated Motility Receptor (HMMR) Encodes an Evolutionarily Conserved Homeostasis, Mitosis, and Meiosis Regulator Rather than a Hyaluronan Receptor

“…The presence of hmmr orthologs amongst invertebrate animals has not been examined likely because arthropods do not express hyaluronan [37]. By using the conserved bZip motif as a landmark, we identified putative hmmr orthologs in many, but not all, orders of insects (Table S1).…”

RHAMM Is a Multifunctional Protein That Regulates Cancer Progression

“…HAS genes are only consistently found in vertebrates, predicting that the capability for producing HA was an important change contributing to vertebrate evolution. HA synthases likely evolved from an ancestral glycosyltransferase that also gave rise to the enzymes that produce related polysaccharides such as chondroitin sulfate, chitin, and even cellulose [ 40 , 47 ]. This is suggested by the following common features: the glycosyltransferases that produce HA, chitin, and cellulose B-1,4 glycan are all integral membrane proteins, have invariant amino acid sequences in their catalytic domains, and can under specific conditions synthesize several polysaccharide products [ 42 , 47 , 48 ].…”