Last year's exam posted

There is a link to last year's exam over on the right-hand side. It's all about the PLP. Well, mostly, anyway.

Protein Modeling Exercise

Instructions for accessing material for the Chem 355 Modeling Project

1. Go to http://dcchem.wikispaces.com/Protein+possibilities and choose a protein from the available list. Edit the page by adding your name; save the page.

2. On the PDB website for your protein, click the "Structure" tab and choose "Download Files." Click "PDB file" to download the file to your computer. Also search for "1HEW" and download the pdb file, as that is the file that will be used in the tutorial.

3. Download the Swiss Viewer (http://www.expasy.ch/spdbv/text/download.htm). The instructions are written for version 3.7 using Mac OS 9 (Classic). There are PC versions and also a beta version of a Mac OS X program. Last year, students used the PC version and the Mac OS 9 version successfully. The tutorial author recommends against using the Mac OS X version. Do not use a beta version!

4. Go to the tutorial/assignment site (http://www.usm.maine.edu/~rhodes/SPVTut/index.html) There is a menu to the left; you will do the first six lessons and then do assignment 1 for your protein.

Opening the file can present a problem -- the default application is generally Graphic Converter on a Mac. I do it this way: hold down the control key, click and hold on the icon for your pdb file. A menu appears. Navigate to "Open With..." and choose "other." Find the Swiss Viewer on the computer and choose it.

Continuing Chapter 5

OK, so I've fallen a bit behind with the postings. We are still covering Chapter 5 material; right now we are part way through the catabolism of tryptophan. Your task for tomorrow is to see if you can figure out how PLP can help with the elimination of alanine from the molecule that we had at the end of the lecture.

The picture is a photomicrograph of alanine.

PLP, an outstanding molecule

Today we started to look at the transformations of amino acids. The first step was to begin an analysis of the chemistry of PLP, a co-enzyme used in a large number of the reactions. The key concept here is that PLP is essentially an electron sink and can generate two different imines. These imines will give different C=O compounds upon hydrolysis. If we are clever about manipulating the PLP adducts we can force the amino acids to undergo a wide variety of changes.

Exam!

Exam! I hope it went well.

The End of Chapter Four

Not much to say about today. We finished Chapter 4 and talked a bit about the exam. Hopefully, everyone will be well-prepared and it will be a positive experience for all!

TCA/Krebs/Citric Acid cycle

Today we made it most of the way through the above-named cycle. For our purposes, the important point is that we start with oxaloacetate, bring in an equivalent of our friend acetyl-
CoA, and then spit out two equivalents of CO2, regenerating oxaloacetate in the process. Lots of familiar processes popped up: NAD+/NADH, E1cb/1,4 addition of water, aldol reaction, decarboxylation........it is worth your effort to make sure that you understand how these processes will work on various organic substrates.

On Wednesday we'll finish up the cycle and get ready for Friday's exam.

The picture is of Hans Krebs.

What about that pyruvate?

No doubt you've always wondered what to do with all of that pyruvate floating around in your body. Now you know a few different things: lactate, ethanol, and acetylCoA all come to mind.

We learned a new system today: TPP ylid, which works as a place-holder for pyruvate, allowing use to add nucleophiles to the C=O. Depending on the nature of the nucleophile, we can effect either an oxidation or reduction of the original pyruvate.

Problem set will be posted later today.

Finishing glycolysis, starting gluconeogenesis

As the title says, we finished glycolysis and started gluconeogenesis. As always, the key is to recognize reaction patterns and think about how they could be used to make a system undergo a particular transformation.

The picture, of course, is Keanu "Neo" Reeves.

Glycolysis

Today we started to look at glycolysis, step by step. We made it about half-way through the process, having broken a six-carbon species down into two equivalent three-carbon species. The "big-ticket" items that we saw included: the use of keto-enol tautomerism to "slide" a carbonyl down a carbon, a retro-aldol to break the six-carbon carbohydrate into two separate three-carbon species, the idea of oxidizing an aldehyde by adding a heteroatom nucleophile and then abstracting a hydride with NAD+, and the concept that all of this can also be done by attaching the molecule to an enzyme covalently through a lysine residue to form an imine.

We'll finish this off on Wednesday and then look at the reverse process.

The picture is of boxing legend "Sugar" Ray Robinson.