Cysteine Metabolism

00:00 Now, homocystinuria, as I said, is a pretty severe disease.

00:05 It's a genetic disease caused by deficiency of this enzyme cystathionine beta-synthase.

00:11 There are many problems that can arise in homocystinuria.

00:15 There are musculoskeletal anomalies that occur. Intellectual disabilities.

00:19 And one of the reasons we have these intellectual disabilities is because of the problems with the nerve tissue in the brain.

00:26 Seizures can result. There are numerous eye anomalies that can arise.

00:30 Vascular disease, because again, we have a lot of homocysteine that's occurring because it's not being converted into cysteine in the process.

00:38 We see cystinuria, which is an unrelated genetic disease that has many symptoms that are similar.

00:45 We have the inability of the kidneys to reabsorb cysteine.

00:48 So, when this happens, then we see problems associated with the kidneys including high levels of cysteine, high levels of lysine, ornithine, and arginine that appear in the urine.

00:58 And because we have these things accumulating, we develop kidney stones that also occur.

01:03 This is not a disease that you would wish on anyone.

01:07 There are at least three other ways of making cysteine and I illustrate these here.

01:11 One of these comes from serine directly.

01:13 In this process, acetylcholine gets - donates an acetyl group to serine to make O-acetyl-L-serine.

01:22 That's shown here. And the next step of the process, the sulfur that ends up being in cysteine, comes with the addition of a hydrogen sulfide.

01:29 This splits out the acetate in the process, leaving behind cysteine for making proteins.

01:36 A second way of making cysteine actually comes from proteins itself. One of the things that cysteine can do in a protein is combine with another cysteine in a covalent bond to make this di-cysteine as were called L-cysteine.

01:49 This involves the joining of the two cysteines together by a disulfide bond shown in the middle of the molecule.

01:56 When proteins are cleaved and they've had this bond occur in them, L-cysteine is the product of the breakdown of the protein.

02:04 Making cysteine from L-cysteine is a trivial matter.

02:07 It simply involves breaking that bond and breaking-that bond involves a reduction.

02:11 The electrons in the process come from NADH, as you can see here. The product of the reaction producing two cysteines.

02:18 The last way of making cysteine starts with an oxidized form of cysteine known as cysteic acid.

02:25 Cysteine is fairly readily oxidized.

02:28 And so, it's not uncommon that cells will have L-cysteic acid within them.

02:33 To make cysteine from that simply involves a reduction, and that reduction involves, again, hydrogen sulfide, as we can see here.

02:41 In the process, the sulfur is donated to the cysteic acid. The sulfite, which was the oxidized sulfur, is released, and cysteine is produced.

02:50 Another member of the cysteine family is that of one of the rare amino acids I talked about earlier.

02:55 This amino acid is known as selenocysteine, and it does not normally occur in proteins.

03:00 It's very rarely appearing.

03:02 And its way of appearing in proteins is unusual and its synthesis is also a little unusual.

03:09 Selenocysteine is sometimes called the 21st amino acid because it's not coded for in the genetic code.

03:16 It uses a stop codon that's in the translational process to get into a protein, and I won't talk about that here.

03:25 The way in which selenocysteine is made is actually made on a transfer RNA.

03:30 Now, the other amino acid who has a modification that occurs on a transfer RNA is that of methionine, and I'll talk about that later in this set of lectures.

03:40 When we look at this process, we see what the way in which selenocysteine is made.

03:45 Selenocysteine synthesis starts with serine, which is why it's in the serine family.

03:50 But serine itself is not directly modified-until after the serine has been joined to a tran fer RNA.

03:57 You'll notice that this is a non-serine transfer RNA.

04:01 So, this is a special transfer RNA that has joined the serine in the process of making selenocysteine.

04:07 So, here we have the product of that reaction. The serine has been linked to this special transfer RNA.

04:14 There are two chemical reactions in which the serine is modified.

04:18 And the modification of the serine involves the alteration of the hydroxyl group to put a seleno group into that.

04:24 Two enzymes are involved known as SEL-A and SEL-D.

04:29 The product of that reaction is this selenocysteine linked to the transfer RNA.

04:34 And the selenocysteine linked to the transfer RNA is then incorporated into proteins using this odd stop codon mechanism of getting it in.

04:43 It's because of this that selenocysteine-is so rarely found in proteins.