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.