Lecture 4

1) Proteins can penetrate and arrange themselves to lie in and out of phospholipid bilayers by having hydrophobic molecules in the region between the membrane and hydrophilic ones on either side. You could also have a positive charged and a negatively charged amino acid in between the membrane, although these are hydrophilic, they satisfy each other’s requirements being oppositely charged.

2) Once a protein has been polymerized, it is not the last thing. Proteins undergo posttranslational modifications. Process of synthesizing a protein is called translation. Further chemical modifications can be imposed on the sidechain to further modify the protein. eg- proteolytic degradation, proteolysis is the degradation of a protein. Or, one part of the protein may simply be clipped off. In many proteins which protrude into the extracellular space, there is another kind of covalent modification, the process of glycosylation, in which a no of sugars is covalently attached to the polypeptide chain, using the hydroxyl of the sidechain of serines for eg. These modify the extracellular domain of the proteins.

3) The hydroxyl chains of carbohydrates offer numerous opportunities for using dehydration reactions or condensation reactions, you remove a water, to attach different things. There are 4 different hydroxyls in ribose that you can use to do that – 1′, 2′, 3′, and 5′. In truth, the 2′ hydroxyl is rarely used. What we have is a glycosytic bond, that is a bond between a sugar and a non-sugar entity. Here a bond is formed between a base and a 1′ hydroxyl of the ribose. At the 5′ hydroxyl, another condensation reaction, called esterification reaction (where acid and base react together, and through a condensation reaction, cause the removal of water.) There are 3 phosphate groups, nearest called alpha, farthest called gamma. This chain of phosphates has very important consequences for energy metabolism and biosynthesis. Because all 3 have negative charge, and hence it takes potential energy to keep them together. And they cannot break apart as long as they are in this triphosphate configuration. But once they are broken apart, the energy released can be used for various purposes.

4) Two basic kind of bases – nitrogenous bases. They aren’t just aromatic rings, infact all of them have nitrogen in the rings. Pyrimidines have 1 six-membered ring, purines have 2 rings, a 5 and a 6 membered ring. What distinguishes one from another is these sidechains.

5) The fact that T has a methyl group doesn’t matter as far as the coding is concerned.

6) Once bases are attached to the sugars, they change their names slightly. The lowest nitrogen participates in the formation of a glycocytic bond. The base + the sugar is called the nucleoside. If on top of that, we add one or more phosphates, it is called nucleotide.

7) Uracil changes its name to uradine when it attaches to the sugar, cytosine changes to cytodine, thymidine, adenicine.

8) Nucleic acid syntesis always occurs in a certain polarity, it goes in a certain direction. You can’t add nucleotides on either end, you can only add them to the 3′ end. The energy of the triphosphate is used to form this bond. The resulting linkage is called phosphodiester linkage. (because there are 2 esterifications) Therefore, polymerization doesn’t take place instantaneously, it requires energy investment of a high energy molecule. This can be repeated. A human chromosome contains 10 mega bases of DNA, million nucleotides.

9) These different bases have complementarity to each other i.e. like to be together with one another. One purine opposite one pyrimidine. If we have two pyrimidines, they are not enough close to each other, whereas if we have two purines they are too close to each other. Polarity of the two chains the constitute the double helix. One runs in 3′ – 5′ direction, other in the opposite direction. We speak of the double helix as being antiparallel.

10) There is specificity here, any purine doesn’t pair up with any pyrimidine. The way they associate with one another is via hydrogen bonds. Therefore, by boiling, we break those hydrogen bonds, remember they have only 8kcal of energy per mole. DNA strands come apart, and the DNA ends up being denatured. If there were a covalent link (instead of a hydrogen bond) between the DNA strands, that’s a bad news for a cell carrying such a DNA molecule, it often means the cell should go off and die. Because the cell has to some day pull apart these strands, and it will have a hard time doing that. So, this association should be tight enough so that its stable at body temperature, but not so tight that it can’t be pulled apart, when certain biological conditions call for it.

11) In C-G, there are 3 hydrogen bonds, in A-T there are 2. The third bond in A-T between H and O cannot be formed because they are very far apart. Each of these base pairs is 3.4Angstroms apart. (distance between two bases on the same strand, so 10 of them make 34 Angstroms) and 10 base pairs is roughly 1 turn of the alpha helix.

12) Information is encoded in two strands, information is redundant. One thing we appreciate is that the phosphates are on the outside, and the bases are on the inside. The bases are protected from the outside world, because the information content in DNA must be held very stable and constant, else we have things like cancer. That’s the reason why the DNA remains stable for 30 thousand years.

13) The structure of the DNA allows it to be copied. Replication. Remember we start out as a fertilized cell with one genome, and throughout our lifestyle we produce, 10^16 cells. We pull apart the two strands, not by putting them in boiling water, but by enzymes whose dedicated function is to put separate those two strands,

14) T and U are from an information point of view, equivalent. We could make a DNA-RNA hybrid helix. The RNA molecule could extract information out, and then leave elsewhere. So extracting information doesn’t mean to destroy it.

15) Often RNA molecules can form intra-molecular double helices. i.e.RNA double strand. This is called a hair pin. They will hydrogen bond to themselves using the complementary sequences. This confers on them very specific structure.

16) Another aspect of the 2 vs 3 hydrogen bonds is the following – if the double helix has many G’s and Cs, then it has more hydrogen bonds holding it together, and you need to put in more energy to denature the double helix.

17) The presence of hydroxyl in RNA has important consequences on the stability of the RNA and the DNA. When hydroxyl ion attacks a phosphodiester bond in an RNA, the phosphodiester bond will try to cyclise producing a 5 membered ring, and ultimately that will resolve and break, causing the cleavage of the RNA chain. That means that if you put RNA molecules in alkali, they will fall apart quickly. What happens to DNA molecules? Nothing, they are alkali resistant, because there isn’t a hydroxyl there to form this 5 membered ring, and alkali cannot cleave apart the DNA. This is another reason why DNA is more stable and lasts for years.


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