Methionine, Threonine and Lysine Metabolism

00:01 Methionine metabolism is kind of complicated as we study it coming from aspartic acid.

00:07 The breakdown of methionine actually overlaps with cysteine metabolism as we briefly seen.

00:12 The complicated synthesis that comes from aspartate, however, I'll show here with a set of arrows.

00:17 Now, the other set of lectures where I've talked about vitamin B12 metabolism, I actually showed those seven reactions.

00:24 So I'm not going to show them again here.

00:25 But suffice it to say that there are seven chemical steps that occur: phosphorylation, an oxidation that accompanies dephosphorylation, another oxidation that occurs, this process creates homoserine.

00:39 Homoserine we remember was an intermediate in the synthesis of the cysteine from methionine.

00:47 Succinylation involves the addition of a succinate molecule.

00:50 The cysteine is replacing the succinate in the next step of the process.

00:55 There's then loss of a pyruvate and an ammonion ion to produce the homocysteine and homocysteine was the molecule we remember whose concentration is a problem in the production of cysteine.

01:07 And finally, methylation of the homocysteine by an N5-methylfolate creates methionine.

01:13 This was the reaction that I described in the other lecture that requires vitamin B12.

01:20 There are other ways of making methionine.

01:22 Homocysteine, as we've seen, can be converted to methionine by the alternate pathway that I'm going to show you here.

01:29 Now, this pathway is another way of getting a methyl group on to homocysteine.

01:34 The difference between homocysteine and methionine is that methyl group.

01:39 So glycine betaine is the source of methyl group here.

01:43 It combines with homocysteine to make dimethylcysteine and methionine.

01:48 So we can see that a methyl group has transferred from the glycine betaine on to the homocysteine to make methionine.

01:55 The enzyme catalyzing this reaction is betaine, homocysteine, methyltransferase.

02:00 And the reaction here occurs in the liver.

02:03 We see the transfer of the methyl group as occurs right here.

02:08 Now, methionine is modified in bacteria before it is put in to making proteins.

02:14 We remember in bacterial translation that the very first amino acid that makes it into the proteins is not methionine but a modified form of it, and that's known as formylmethionine.

02:25 So this set of reactions I'm going to show you shows how that formylmethionine is made.

02:31 Like the synthesis of selenocysteine, formylmethionine is made by modifying a methionine tha's on a transfer RNA.

02:40 This is shown in the set of reactions.

02:42 Methionine combines first with its initiation tRNA that's used to put it into the protein during the process of translation.

02:49 This produces the methionine joined to the tRNA.

02:54 And then the reaction that makes formlymethionine, we see that the formyl group actually comes form 10 formyltetrahydrofolate and produces the formulated methionine on the transfer RNA.

03:08 The product to that reaction makes tetrahydrofolate.

03:11 And the enzyme catalyzing in this Methionyl-tRNA formyltransferase.

03:16 The next amino acid metabolism we will consider as that of threonine.

03:20 Threonine's metabolism overlaps a bit with methionine metabolism.

03:24 The first three steps of the synthesis of threonine from aspartate are the same as first three steps in the synthesis of methionine.

03:31 The aspartate is converted to aspartyl-beta-phosphate by a phosphorylation.

03:36 The aspartyl-beta-phosphate is converted to beta-aspartate semialdehyde by a reduction.

03:42 And the homoserine is created from the last intermediate by a reduction as well.

03:47 These three steps also happen in the synthesis of methionine.

03:51 In the next step of the process, homoserine is phosphorylated to make phosphohomoserine using energy from ATP.

03:58 And then phosphohomoserine is dephosphorylated and that dephosphorylation involves a molecular rearrangement, that molecular rearrangement producing threonine.

04:07 This whole process involves the use of 2 ATP and 2 NADPH molecules. Lysine is made in also another set of very complicated reactions.

04:18 The first two reactions are same as threonine and methionine metabolism.

04:22 There are total of nine steps.

04:24 I'm not going to step you through all of those here because they're not really relevant or needed for us to understand what's happening in the process.

04:30 Lysine is one of the most post-translationally modified amino acids and we'll talk about that at the end of this set of lectures.

04:38 It's very important for that the modifications that happen to lysine allow for so many things to happen in the cells.

04:44 The hydroxylation of lysine, we've seen in another lecture, is important for making strong collagen.

04:51 And a deficiency of one of the enzymes in the lysine pathway, an alpha-aminoadipic semialdehyde synthase, leads to hyperlysinemia.

04:59 And hyperlysinemia leads to accumulation of lysine in the blood which has some very severe consequences.