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.

The End of Chapter Three

Today we finished our treatment of the biosynthesis of fatty acids. This was the end of the material that we will cover in chapter three. We then had a look at some of the big topics that came up in this chapter: catalytic triad, FAD/FADH2 redox, NADH/NAD+ redox, ATP for making leaving groups at carboxylic acid centers, biotin/bicarbonate-mediated manufacture of CO2, non-H pro-R and pro-S atoms, etc.

Fatty Acid synthesis

Yesterday we started to look at the process by which acetylCoA is converted to fatty acids (the reverse of the process that we had been studying). The major new process was the use of biotin-mediated reaction of ATP/bicarbonate/acetylCoA to transfer a carbon dioxide to acetylCoA and manufacture malonylCoA. We also saw that there were a number of transthioesterifications and the use of our friend NADH in a reduction, followed by an E1cb elimination. We'll finish this off tomorrow.

Chopping Up Fatty Acids

Today we continued our look at what happens to by-products of triacylglyceride catabolism. The topic was the degradation of fatty acids to acetyl-CoA. In order to understand the process it was necessary to learn the inner workings of a new redox system -- FAD/FADH2. The difficult issue here is that you must use both "fishhook" arrows and regular electron pair arrows as part of the same mechanism. Once over that issue, it is generally not too bad.

The last part of the degradation involved a 1,4 addition to an alpha, beta unsaturated thioester, an NADH/NAD+ oxidation and a retro-Claisen. All are things that we have seen before, it is just a matter of being able to get our hands around them in the more complicated-looking world of biomolecules.

The dog pictured came up when I did an image search for "FADH2." Perhaps that is his name.

Chapter 3

We finally started looking at real bioorganic chemistry on Wednesday and Friday. On Wednesday we looked at lipid metabolism and learned how biological systems use the catalytic triad as a way of manufacturing hydroxide for a reaction, but keeping [hydroxide] equal to (essentially) zero. In this way, fatty acid esters are converted to alcohol and carboxylic acid. Here, it is all about the electron flow.....

We also saw how to go backwards from acid and alcohol to fatty acid ester. This process a little more complicated and required that we use acetyl-CoA to create thioesters and ATP to create acyl phosphates from carboxylic acids.

Friday's focus was on the conversion of glycerol to dihydroxyacetone phosphate. Several important points came up in this one: you don't need to limit pro-R and pro-S designations to hydrogens (we saw how to label the CH2 groups in glycerol), the ATP-mediated phosphorylation is used again (this time on an alcohol instead of an acid), and the use of the NAD+/NADH system to mediate redox chemistry. This last part was the hardest, requiring that we understand how NADH acts as a stereospecific source of hydride and how NAD+ acts as a hydride acceptor in what is essentially an elimination of dihydrogen from across a C=O bond.

Exam Day!

In case you weren't paying attention, we had an exam today. I hope it went well!

Finishing Chapter 2

Some basic p-chem stuff today, mostly about how enzymes do their enzyme thing and how the energy of the system is manipulated by biological systems by coupling an exergonic process (often hydrolysis of ATP) to a needed endergonic process.

We also went over question #10 from the end of Chapter 2.

Biomolecules, Volume 2

Nucleic acids and amino acids. What a pair. Today's lecture dealt with the two classes of compounds mentioned above, with some commentary on how they can be strung together to form larger biomolecules. With nucleic acids, it was the recognition of the 3' - 5' coupling; the resultant macro structure is held together in helical form largely by non-covalent forces (in this case, hydrogen bonds). As for amino acids, we saw how they exist in zwitterionic form in aqueous solution. There are a variety of different types of side chains that can be attached which can be broken up into the generic catagories of neutral, acidic, and basic.

Chains of amino acids make peptides, many enzymes and proteins are nothing other than amino acids. The overall structure can be described as primary (1°, the order of amino acids), secondary (2°, local interactions such as helices, sheets and turns), and tertiary (3°, the complete three-dimensional structure).

The picture, as promised, is from Kill Bill, Volume 2.

Biomolecules, Volume 1

Today we talked about lipids and carbohydrates. There wasn't a lot of exciting information but you should be able to identify various types of biomolecules and you should be able to show an understanding of carbohydrates (simple/complex, aldose/ketose, D/L, etc.). I have posted a copy of last year's exam #1 (on the right).

The picture, of course, is from Kill Bill, Volume 1.

Useful chapter 2 questions: 1, 3, 4, 6, 7, 8, 10, 15, 16, 20

Stereocenters

Today was a day to go over a lot of material regarding stereocenters. We covered everything from standard (R) and (S) configurations to enantiomers and diastereomers. Most of the class was spent trying to figure out how to separate a pair of enantiomers; in the end we came up with the idea of adding a second stereocenter of known configuration in order to make a pair of diastereomers and then separating those.

New topics dealt with prochirality, the concept of atoms that could be stereocenters if we did something to them. There are two kinds: Faces, which are termed re and si, depending on the orientation of substituents according to CIP rules; and pro-R/pro-S, in which we decide what stereochemistry an atom would have IF we made a change to one of the substituents (typically, converting an H to a D).

The picture shows si and re faces of F420 and NADPH. We will learn about such things soon!

Mechanisms, Sweet Mechanisms

Today we looked at lots of mechanisms from organic. It was pretty much a review of things you already knew (or knew at one time) with a few comments on how these reactions could come into play in bioorganic chemistry.

Friday will start Chapter 2 with an emphasis on stereochemistry.

First Day!

A pretty easy first day of class -- background information, a review of the syllabus and semester grid, and a brief look at functional groups. On Wednesday we'll get into a review of organic mechanisms. In the meantime, some useful questions for the end of chapter one: 1, 3, 4, 5, 6, 7, 8a, 8b, 13

We also took the class picture. A handsome group of students!

Welcome!

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