Biosynthesis of Long Chain Base in Sphingolipids in animals, Plants and Fungi

Abstract

Long chain base (LCB) is a unique building block found in sphingolipids. The initial step of LCB biosynthesis stems from serine:palmitoyl-CoA transferase enzyme, producing 3-ketodihydrosphingosine with multiple regulatory proteins including small subunit SPT a/b and orosomucoid-like protein1-3. 3-Ketodihydrosphingosine reductase and sphingolipid Δ4-desaturase, both of them poorly characterized mammalian enzymes, play key roles for neurological homeostasis based on their pathogenic mutation in humans. Ceramide synthase in mammals has six isoforms with distinct phenotype in each knockout mouse. In plants and fungi, sphingolipids also contain phytosphingosine due to sphingolipid C4-hydroxylase. In contrast to previous notion that dietary intake might be its major route in animals, emerging evidences suggested that phytosphingosine biosynthesis does occur in some tissues such as the skin by mammalian C4-hydroxylase activity of the DEGS2 gene. This short review summarizes LCB biosynthesis with their associating metabolic pathways in animals, plants and fungi.

Phytosphingosine induces systemic acquired resistance through activation of sphingosine kinase

“…PHS influences the composition of sphingolipid metabolites in the next steps of SPT was further investigated. Transcription of alkaline ceramidase ( ACER3 ), which hydrates unsaturated ceramides, dihydroceramides, and phytoceramides to form LCBs such as PHS or sphingosine (Mashima et al, 2020), was effectively elevated, by approximately 63%, after 48 h of PHS treatment compared to that after Ppn inoculation (Fig. 6E).…”

“…Moreover, sphingolipid metabolites have recently drawn attention as second messengers for stomatal closure, programmed cell death (PCD), and defense against pathogen attack in response to abiotic and biotic stresses in plants (Markham et al, 2013; Magnin-Robert et al, 2015; Glenz et al, 2019). Although the physiological roles of sphingolipid have been extensively studied in animals (Mashima et al, 2020), it remains unclear what mechanism is responsible for their physiological action in plants.i…”

“…Sphingolipid biosynthesis is initiated in the endoplasmic reticulum (ER) by condensation of serine with palmitoyl-coenzyme A catalyzed by serine palmitoyltransferase (SPT), resulting in the production of the LCB 3-ketodihydrosphinganine, which is then reduced to dihydrosphingosine (d18:0) (Chao et al, 2011). Dihydrosphingosine is further modified to phytosphingosine (t18:0) (PHS) by the introduction of a double bond into the LCB in plants and fungi (Berkey et al, 2012), as well as to sphingosine, a free form of long-chain sphingoid base, in mammals (Mashima et al, 2020). The highest proportion of PHS, a trihydroxylated LCB, has been reported in the leaves of tobacco ( Nicotiana tabacum and Nicotiana benthamiana ) with large proportions of d18:2 and t18:1 (Cacas et al, 2012).…”

Identification of Compounds with Potential Therapeutic Uses from Sweet Pepper (<em>Capsicum annuum</em> L.) Fruits and Their Modulation by Nitric Oxide (NO)

“…However, phytosphingosine has a hydroxyl group in carbon C4 from the sphingoide large chain, whilst sphingosine and ceramide contain a trans double bond between C4=C5 [87]. Phytosphingosine has been reported in microorganisms, yeasts, plants, fungi, and mammal cells as an essential component of the membrane, playing key roles in cell growth, survival and cell death, and mediating the response against stress as secondary messengers [92][93][94][95]. In plants, it has been reported that phytosphingosine participates in plant stress signaling through crosstalk-regulated events [96], and it has been also found that this compound obtained from wheat root exudates displays anti-fungal activity on the rhizosphere microbial community associated with watermelon [97].…”

Biomarkers for Lysosomal Storage Disorders with an Emphasis on Mass Spectrometry

“…Emerging evidence demonstrates that LysoGb3 detected in the urine and plasma contains some variant substances [13]. Although the biosynthesis mechanism of LysoGb3 remains to be fully characterized, it is commonly accepted that LysoGb3 is generated from the enzymatic reaction of serine:palmitoyl transferase, a rate-limiting enzyme for sphingolipid biosynthesis [14]. In this case, long chain base (LCB), a building block of sphingolipids, is d18:1 representing a C18 aliphatic lipid with a double bond between C4-C5 with trans geometry and two hydroxyl groups.…”