Friday, July 15, 2011

Foxfire: Chemistry of the undead

Ghostly mushrooms

I am currently approaching the half way mark in my current work-in-progress (WIP-2) and have been making particularly heavy use of foxfire.  I didn't start out to write about that... in fact, this book started out as a humorous middle grade adventure and quickly turned into a dark, YA biopunk.  Write what you know, I suppose.  One of the emerging themes is the struggle between the protagonists and the technologically-advanced fungi that exists in their (slightly dystopian) world.  So, I found it a little coincidental that a report came out a week ago by Marina Capelari and colleagues about a type of ghost mushroom that had been re-discovered in a Brazilian rainforest after being extinct for over 150 years (abstract in the journal Mycologia).  The mushroom, formerly known as Agaricus gardneri, is notable for its bright and constant bioluminescence.  To understand why this is unusual, here is a brief description of how foxfire comes to be:

Bioluminescence is generally accepted to come from a 2-step reaction.  A chemical called luciferin (L) is first reduced (to LH2) and this reaction is catalyzed by an enzyme called reductase.  NADH is a molecule (di-nucleotide, actually) that is a cofactor in many redox reactions.  Its basic function is to move protons around (you're a geek if you noticed the chemistry pun).

L + 2NADH <--> LH2 + 2NAD+

Reduced luciferin is then oxidized (to LO) by an enzyme called luciferase.  This process also produces a photon of light and is the source of the creepy glow.

LH2 + O2 <--> LO + H2O+ LIGHT

Illudin S: Potential substrate for ghost fungi
Why am I cryptically showing fungal luciferin as L, instead of showing the chemical structure?  Could it be that my chemistry skills are so bad, I couldn't tell the difference between L and LH if my life depended on it?  Well, yes -- but it is also true that the luciferase substrate in fungi is not well characterized. The luciferin for A.gardneri is probably a member of the sesquiterpene family, most likely an illudin.  Some of these compounds have been studied as anticancer agents but the illudins tend to be extremely toxic (possibly another reason they are called ghost mushrooms!).  Interestingly, other luciferins (such as those found in fireflies, shrimp, etc) have totally different chemical structures, which gives them different biological properties and unique spectral characteristics (ie, different colors, brightness, etc).  Changes in the luciferin structure, amino acid substitutions in the active site of luciferase, and varying levels of oxygen or water can each contribute to changes in the emission of light.  What is unusual about A. gardneri is that unlike other species, the bioluminescence is almost constant.  In fireflies, the luciferin is released when they want to blink and in the case of other species, they light up only after contact (probably a means of self-defence).  So why does this mushroom glow all the time? No one knows yet.  The biochemistry of these things is almost as mysterious as seeing their eerie ghostly glow on some rotting tree stump at midnight.

However, it provides a great real-world example of the potential technology for my story.  It doesn't take much imagination to think that these mushrooms could be engineered to be very bright or to respond in controlled ways depending on environmental input.  A basic example from my WIP is that these types of fungi are used for lighting underground.  No electricity required, no pollution, and little maintenance.  They are almost the perfect type of lighting... or are they?  Anyhow, I thought it was a pretty clever idea early on until I found out that Ben Franklin used foxfire from mushrooms to light the inside of one of the first submarines.  Was there anything this guy didn't know about?  I guess he's going to have to go on my list of card-carrying biopunks.

Friday, July 1, 2011

Resveratrol from red wine: An exercise mimetic?

I've posted before about the magic of polyphenols in wine.  A new paper out by Iman Momken et al. in the FASEB Journal (abstract)  now suggests that one of these polyphenols can protect against muscle wasting and bone loss as a result of inactivity.  The group suspended rats by the tail to prevent their hind limbs from significant weight-bearing exercise in an attempt to model the situation during spaceflight (the main focus of the paper).  One group was treated with resveratrol (aka RES, a red wine polyphenol) at 400 mg/kg per day and compared to a control group receiving no treatment or normal rats (no leg suspension).  Over a two-week period, they studied both the physiological changes in the muscle and bone, as well as biochemical pathways involved to better understand the biological function of the polyphenol. 

The physical benefits were fairly clear.  They observed significantly reduced muscle atrophy and much less bone demineralization in RES-treated rats, suggesting that the compound was protective.  The interesting aspect was in the biochemical details.  It is well known that extreme lack of muscle usage (for example, in cases of long-term bed rest) can induce insulin resistance in humans.  In this study, they claimed that rats treated with RES did not lose insulin resistance. However, I thought this was the least convincing data in the paper.  Some of the differences were significant, but I thought the overall effect on insulin/glucose levels was pretty modest.

A much more convincing effect was observed in the bone and muscle.  They monitored a number of biochemical parameters and found that suspension of the hind limb led to significant changes in the morphology and function of muscle tissue.  All of these changes were consistent with atrophy.  Rats in the control group did not have this effect.  In the RES-treated group, suspension of the hind limb was found to produce little or no changes to muscle.  Then they show that specific biochemical pathways are involved in the protective effects of resveratrol, particularly those involved in oxidative stress and fatty acid metabolism. In plain English, they found that even though there was no weight-bearing exercise to stimulate cellular activity, resveratrol was able to preserve these activities and prevent muscle degradation.  That is, it acted almost like an exercise mimetic.

Does this mean we can forget the gym and just drink our way to better health? Can we have a glass or two of wine while watching Buffy the Vampire Slayer and call it exercise?  Probably not.  The amount of resveratrol in a typical glass of wine is less than a milligram.  The 250g rats in this study received 100 mg, so the observed benefit came from the equivalent of 100 glasses of wine per day.  Your muscles are really gonna need that resveratrol if you spend every day passed out next to the TV.  However, it does further illustrate the potential health benefits of these wonderful polyphenols.  Maybe on those cold, snowy days in winter you can just pop a RES pill and get the same benefit as a walk around the neighborhood. For you health nuts, you can chase it down with a glass of good Cabernet.