4 research outputs found
Cannabis for medical use: versatile plant rather than a single drug.
Medical Cannabis and its major cannabinoids (−)-trans-Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) are gaining momentum for various medical purposes as their therapeutic qualities are becoming better established. However, studies regarding their efficacy are oftentimes inconclusive. This is chiefly because Cannabis is a versatile plant rather than a single drug and its effects do not depend only on the amount of THC and CBD. Hundreds of Cannabis cultivars and hybrids exist worldwide, each with a unique and distinct chemical profile. Most studies focus on THC and CBD, but these are just two of over 140 phytocannabinoids found in the plant in addition to a milieu of terpenoids, flavonoids and other compounds with potential therapeutic activities. Different plants contain a very different array of these metabolites in varying relative ratios, and it is the interplay between these molecules from the plant and the endocannabinoid system in the body that determines the ultimate therapeutic response and associated adverse effects. Here, we discuss how phytocannabinoid profiles differ between plants depending on the chemovar types, review the major factors that affect secondary metabolite accumulation in the plant including the genotype, growth conditions, processing, storage and the delivery route; and highlight how these factors make Cannabis treatment highly complex
Triple-Stage Mass Spectrometry Unravels the Heterogeneity of an Endogenous Protein Complex
Protein
complexes often represent an ensemble of different assemblies
with distinct functions and regulation. This increased complexity
is enabled by the variety of protein diversification mechanisms that
exist at every step of the protein biosynthesis pathway, such as alternative
splicing and post transcriptional and translational modifications.
The resulting variation in subunits can generate compositionally distinct
protein assemblies. These different forms of a single protein complex
may comprise functional variances that enable response and adaptation
to varying cellular conditions. Despite the biological importance
of this layer of complexity, relatively little is known about the
compositional heterogeneity of protein complexes, mostly due to technical
barriers of studying such closely related species. Here, we show that
native mass spectrometry (MS) offers a way to unravel this inherent
heterogeneity of protein assemblies. Our approach relies on the advanced
Orbitrap mass spectrometer capable of multistage MS analysis across
all levels of protein organization. Specifically, we have implemented
a two-step fragmentation process in the inject flatapole device, which
was converted to a linear ion trap, and can now probe the intact protein
complex assembly, through its constituent subunits, to the primary
sequence of each protein. We demonstrate our approach on the yeast
homotetrameric FBP1 complex, the rate-limiting enzyme in gluconeogenesis.
We show that the complex responds differently to changes in growth
conditions by tuning phosphorylation dynamics. Our methodology deciphers,
on a single instrument and in a single measurement, the stoichiometry,
kinetics, and exact position of modifications, contributing to the
exposure of the multilevel diversity of protein complexes