August 8th, 2008 ecoli
Last night I was cutting up some of my homegrown Serrano chilies. I made a pretty good salsa with them (thanks to iNow for the recipe). However, I wasn’t prepared for the extreme heat of the peppers. I bit into one and my mouth almost literally caught on fire. I ignored the pain though and finished the salsa. About an hour later my hand started to burn and no amount of soap and water would significantly reduce the pain. As of right now, I’m still feeling it.
Being the naturally curious person, I wanted to find out more about why my hand felt like it was being knawed on by a million angry Gremlins.
Enter Capsaicins, the active ingrediant of the spicy heat of chilis:
Its a hydrophobic compound (which would explain why the water didn’t help) colorless and odorless but certainly not tasteless. It’s also an irritant for all mammals. Capsaicin is the most abundant of the capsaicinoid molecules found in chili peppers. The structure was first defined in 1919 by E. K. Nelson.
The capsaicins are found most abundantly in the placental tissue of the fruit. That is mainly the inner membranes and the white tissue holding the seeds, known as the pith, but not actually in the seeds themselves and in small amounts in the outer skin. Birds, which lack capsaicin receptors eat chilies and distribute their seeds after they pass safely through their digestive tracts.
In diluted form, the capsaicins are great for food, but can cause burning sensations when exposed in high concentrations to mucus membranes and skin, as I have discovered. The Scoville scale is a relative measure of how hot a pepper is, on the basis of perception. To demonstrate the scale, a bell pepper would get a zero rating, jalapenos are 2500-8000 (I assume non-pickled). My serranos would be rated around 10000 to 23000 and habeneros are 100000 to 350000. The Dorset Naga (yes grown in Dorset, England) tops the scales at 876,000 to 970,000. Nothing beats pure capsaicin, however, which weighs in at a hefty 15000000 on the Scoville scale.
So why do these capsaicins hurt so much? Its because they interact with sensory neurons. Capsaicins bind to vanilloid receptor subtype 1, an ion channel receptor which can also, incidently be stimulated by heat and abrasions. When opened, the channels allow calcium cations to pass through, depolarizing the cell membrane potential. From here, the electrical signal propogates down the neuron and is percieved ultimately in the brain.
So the reason why chilies make you feel like your toungue or hands are on fire, is because that’s exactly how your brain intepretes the neuronal signals. Of course, you know that there’s no actual heat present but, in this case perception is reality. Its nice to know that, while it may feel like you tounge is going to fall off, the capsaicins probably won’t cause real physical damage. However, it is an irritant, so injesting a large amount can be reasonto call the poison control center.
On the plus side, capsaicinoids have been useful in medicine, from treating topical pain in neuropathy to treating cancers and diabetes. Capsaicins can be a part of a healthy diet, as shown in epidemiological studies. Regions, such as Thailand, which use a healthy amount of chilies in their cooking have lower incidence of GI cancers. Capsaicins have been shown to promote apoptosis in lung cancer cells. New research also suggests that capsaicins could help reduce drug dependency.
So chilies taste good and are good for you, as long as you don’t over-ingest.
I can’t wait to go home and try my hot salsa.
Posted in biochemistry, medicine, neurobiology | 10 Comments »
June 25th, 2008 ecoli
Thanks to bascule at SFN for this link.
Richard Lenski, whose groundbreaking work witnessed the evolution of citrate-using E. coli in a mere 44,000 generations over 20 years of work.
He responds directly to conservapedia’s ignorant creationism populace published by conservapedia (amazingly enough) here:
Lenski’s second letter is particularly good, filled with lots of good biochemistry, scientific philosophy and general good sense. A highly recommended read.
Discuss the exchange here.
Posted in biochemistry, creationism, evolution, link out, microbiology | 3 Comments »
May 22nd, 2008 ecoli
This blog post is my entry for Skull’s in the stars’s challenge.
- Beadle and Tatum, 1941
About 15 years before Watson and Crick proposed a model for DNA and back when scientists were in disagreement about how genetic information was actually stored, there was the Beadle and Tatum experiment. 
In 1941, American geneticists George Beadle and Edward Tatum, at Stanford University, rediscovered the ideas of the British physician, Archibald Garrod; who, in 1909, proposed that a single gene was responsible for the production of a single protein. Garrod was studying an inherited disease known as alkaptonuria, the production of red colored urine due to an enzyme deficiency.
Based on this work, which had gone largely ignored until then, Beadle and Tatum proposed that, if the “one gene, one enzyme” hypothesis is true, they should be able to produce mutant organisms (in this case the bread mold, Neurospora crassa) with a single gene mutation, corresponding to a single defunct enzyme.
Keep in mind, this is before DNA and cloning experiments and long scientists knew how to produce specific genetic knockouts. Beadle and Tatum, therefore, had to induce non-specific mutations with x-ray and UV radiation. But, by controlling the growth media of the Neurospora, they were able to identify single mutations in biochemical pathways of amino acid synthesis.
Mutated Neurospora was grown in a medium containing all 20 biological amino acids, and the mutated spores were subsequently crossed with wild type spores. Next, the next generation of spores were grown in a medium containing one one of the essential amino acids. If, for example, there was a mutation in a protein that synthesized proline, then the spore would only grow if proline was in the medium (For more background information on amino acid biosynthesis pathways, this is a good resource). Using this method, they were able to link the mutation of a specific gene (which was demonstrated in 1926 by Hermann Joseph Muller) the disfunction of an enzyme related to the synthesis of a specific amino acid.
As in interesting side note to the overall purpose of the experiment, was that they discovered a way by which they could determine the complexity of a specific pathway, by describing pivotal genes, and their enzymes:
in addition to minimal media controlling just the amino acid content, other vitamins and nutrients where also controlled, vitamin B6, for example they realized they could use their technique in a different way. This was a method which they could use to discover entire new pathways, discovering what vitamins and nutrients are essential to growth, and what pathways they are involved in:
The Beadle and Tatum experiment was later revised to include all classes of polypeptides, and not just enzymes, into the “one gene” idea. But, it was their work that was seminal in providing a to link the fields of biochemistry and genetics, providing a way to look at biochemical pathways and protein enzymes through the lens of genetic information, paving the way for later scientists like Watson and Crick, and many others.
Beadle and Tatum shared a Noble Prize in Medicine or Physiology (1958) for their work. A copy of their original paper can be viewed here, I believe for free.
Posted in biochemistry, genetics, microbiology, musings | 32 Comments »
April 29th, 2008 ecoli
What’s one of the first thing students learn in high school about nucleic acid molecules? It’s that DNA is double stranded and RNA is single stranded. Not only is this fundamentally incorrect, such type of “linear” thinking is, I would argue, a ‘dangerous’ line of thinking, that may be hard for students to escape from.
Any biochemistry student can tell you that, not only can certain types of RNA form secondary and tertiary structures, but that these structures are critical to understanding the catalytic activity of RNA. This has important revelations for evolution (the RNA-first world hypothesis) and for molecular biology.
Microbiology Bytes ran a segment on The shape of HIV RNA (see image below). The higher order, 3 dimensional structure of HIV RNA could play some important role in viral replication and pathogeneiss
This example serves to illustrate the important point that higher order RNA structure could more important in biology than we could have imagined. Therefore, if we keep giving students the impression that RNA (and other molecules) are linear and static, than they could carry with them a false veiw of biological models.
Coincidently, this also is another reason that computational and mathematical modeling in biology will become all important in the coming years. As it turns out, biochemical structures are just too complex to realistically model without computers (at least not easily).
And, as it turns out, even knowing three dimensional structures may not be enough. Carlos Simmerling from Stony Brook University does computational modeling of biomolecular systems (specifically proteins and nucleic acids) as dynamic entities. In other words, intra-interactions, as predicted by mechanics, cause molecules to “move and shake.” These molecular “vibrations” caused by electrostatic interactions could also greatly potentially affect reactivity of molecules in ways we could have never predicted without computer modeling. Simmerling also develops tools to view these molecules in their energetic states. Here’s a video from Simmerling’s group of the enzyme HIV Protease.
These developments stress the need for new scientists (yes, even biologists) to think mathematically and artistically. We need to be aware of all three dimensions (plus the time dimension) in order to work towards building accurate models of biological and biochemical systems.
Posted in biochemistry, link out, microbiology, musings | 4 Comments »
April 22nd, 2008 ecoli
It is well known now that eukaryotic genomes contained gene sequences that are expressed (exons) and intervening sequences that are unexpressed, introns. How are introns removed from the genetic code, and how are intron sequences recognized?
Transcription of DNA occurs wholly. So, when messenger RNA is built by RNA polymerase from the DNA template, the introns are included in this sequence. After mRNA is capped, and elongation of transciption begin intron splicing can occur. After introns have been spliced, the product is mature mRNA, which is then polyadenylated.
Intron-exon junctions studies show that there is a high degree of homology between eukaryotes, the consensus sequence being an invariant GU sequence at the 5′ intron boundary and an AG invariant sequence at the 3′ boundary. These two sequences are all that is required to define a splicing boundary (as we’ll see later).
There are actually 4 different types of introns, but I will focus on the first two types, which work via two general mechanisms, known as Group 1 and Group 2 (creative, I know). Type 1 introns are self splicing and are employed in nuclear, mitochondrial and chloroplast rRNA, tRNA and mRNA. Type 2 introns are also self splicing, and are used in genes in mitochondria and chloroplasts of fungi algae and plants. Type 3 introns require a spliceosome and small nuclear Ribonucleo Proteins (snRNPs) and are responsible for solely eukaryotic splicing. Type 4 introns require ATP and an endonuclease.
As can be seen in the figure, in Type 1 introns, the 3′ OH group of a free guanosine acts a nucleophile, attacking the 5′ phosphate at the splice site, displacing it from the exon. The 3′ OH at the exon, usually a U, acts as a nucleophile, atacking the phosphodiester bond, removing the other end of the intron, and reforming the phosphodiester bond with itself.
In Type II introns, a similar mechanism is used, except that an internal 2′ OH of an adenoside is used as the nucleophile, attacking the 5′ splice site of the exon to produce a lariat structure. In the final step, the 3′ OH of the 5′ exon attacks the phosphodiester bond of 3′ uracil, to remove the lariat.
In type III introns, a lariat structure is formed, but the snRNPs are used to form the secondary structures and to mediate the reaction, though it still occurs without free energy input. There are 6 snRNP subunits that make up the splicesome.
Intron sequences are recognized by short sequence elements within exons, known as exonic sequence/splicing enhancers (ESEs). But the mechanism by which they function is poorly understood. The fact that the splicing process occurs contemporaneously with RNA polymerase transciption elongation allows for the immediate splicing upon the recognition of an exon-intron junction sequence, and may account for the high accuracy of this system. Additionally, some evidence suggests that the C-terminal domain of RNAP II itself helps to tether the exon and splicing machinery together.
Posted in biochemistry | 4 Comments »
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