biology

Phosphatidylethanolamine N-methyltransferase

Phosphatidylethanolamine N-methyltransferase is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Phosphatidylethanolamine N-methyltransferase rather than just read about it. In short: Phosphatidylethanolamine N-methyltransferase (abbreviated PEMT) is a transferase enzyme (EC 2.1.1.17) which converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) in the liver. In humans it is encoded by the PEMT gene within the Smith–Magenis syndrome region on chromosome 17.

Key takeaways

Phosphatidylethanolamine N-methyltransferase belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Phosphatidylethanolamine N-methyltransferase to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Phosphatidylethanolamine N-methyltransferase from memory before moving on to harder problems.

Reference excerpt

Phosphatidylethanolamine N-methyltransferase (abbreviated PEMT) is a transferase enzyme (EC 2.1.1.17) which converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) in the liver. In humans it is encoded by the PEMT gene within the Smith–Magenis syndrome region on chromosome 17. While the CDP-choline pathway, in which choline obtained either by dietary consumption or by metabolism of choline-containing lipids is converted to PC, accounts for approximately 70% of PC biosynthesis in the liver, the PEMT pathway has been shown to have played a critical evolutionary role in providing PC during times of starvation. Furthermore, PC made via PEMT plays a wide range of physiological roles, utilized in choline synthesis, hepatocyte membrane structure, bile secretion, and very low-density lipoprotein (VLDL) secretion.

Nomenclature Phosphatidylethanolamine N-methyltransferase is also known as lipid methyl transferase, LMTase, phosphatidylethanolamine methyltransferase, phosphatidylethanolamine-N-methylase, and phosphatidylethanolamine-S-adenosylmethionine-methyltransferase.

Function

The PEMT enzyme converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) via three sequential methylations by S-adenosyl methionine (SAM). The enzyme is found in endoplasmic reticulum and mitochondria-associated membranes. It accounts for ~30% of PC biosynthesis, with the CDP-choline, or Kennedy, pathway making ~70%. PC, typically the most abundant phospholipid in animals and plants, accounts for more than half of cell membrane phospholipids and approximately 30% of all cellular lipid content. The PEMT pathway is therefore crucial for maintaining membrane integrity. PC made via the PEMT pathway can be degraded by phospholipases C/D, resulting in the de novo formation of choline. Thus, the PEMT pathway contributes to maintaining brain and liver function and larger-scale energy metabolism in the body. PC molecules produced by PEMT-catalyzed methylation of PE are more diverse, and tend to contain longer chain, polyunsaturated species and more arachidonate, whereas those produced via the CDP-choline pathway are typically composed of medium-length, saturated chains. A major pathway for hepatic PC utilization is secretion of bile into the intestine. PEMT activity also dictates normal very low-density lipoprotein (VLDL) secretion by the liver. PEMT is also a significant source and regulator of plasma homocysteine, which can be secreted or converted to methionine or cysteine.

Mechanism The exact mechanism by which PEMT catalyzes the sequential methylation of PE by three molecules of SAM to form PC remains unknown. Kinetic analyses as well as amino acid and gene sequencing have shed some light on how the enzyme works. Studies suggest that a single substrate binding site binds all three phospholipids methylated by PEMT: PE, phosphatidyl-monomethylethanolamine (PMME) and phosphatidyl-dimethylethanolamine. The first methylation, that of PE to PMME, has been shown to be the rate-limiting step in conversion of PE to PC. It is suspected that the structure or specific conformation adopted by PE has a lower affinity for the PEMT active site; consequently, upon methylation, PMME would be immediately converted to PDME and PDME to PC, via a Bi-Bi or ping-pong mechanism before another PE molecule could enter the active site.

Structure Purification of PEMT by Neale D. Ridgway and Dennis E. Vance in 1987 produced an 18.3 kDa protein. Subsequent cloning, sequencing, and expression of PEMT cDNA resulted in a 22.3 kDa, 199-amino acid protein. Although the enzymatic structure is unknown, PEMT is proposed to contain four hydrophobic membrane-spanning regions, with both its C and N termini on the cytosolic side of the ER membrane. Kinetic studies indicate a common binding site for PE, PMME, and PDME substrates. SAM binding motifs have been identified on both the third and fourth transmembrane sequences. Site-directed mutagenesis has pinpointed the residues Gly98, Gly100, Glu180, and Glu181 to be essential for SAM binding in the active site.

Regulation PEMT activity is unrelated to enzyme mass, but rather is regulated by supply of substrates including PE, as well as PMME, PDME, and SAM. Low substrate levels inhibit PEMT. The enzyme is further regulated by S-adenosylhomocysteine produced after each methylation. PEMT gene expression is regulated by transcription factors including activator protein 1 (AP-1) and Sp1. Sp1 is a negative regulator of PEMT transcription, yet is it is a positive regulator of choline-phosphate cytidylyltransferase (CT) transcription. This is one of several examples of the reciprocal regulation of PEMT and CT in the PEMT and CDP-choline pathways. Estrogen has also been shown to be a positive regulator of hepatocyte PEMT transcription. Ablation of the estrogen binding site in the PEMT promoter region may increase risk of hepatic steatosis from choline deficiency.

Disease relevance

Liver

PEMT deficiency in mice, genetically induced by PEMT gene knockout, produced minimal effect on PE and PC levels. However, upon being fed a choline-deficient diet, the mice developed severe liver failure. Rapid PC depletion due to biliary PC secretion, as well as protein leakage from loss of membrane integrity due to lowered PC/PE ratios, led to steatosis and steatohepatitis. A Val-to-Met substitution at residue 175, leading to reduced PEMT activity, has been linked to non-alcoholic fatty liver disease. This substitution has also been linked to increased frequency of non-alcoholic steatohepatitis. A single-nucleotide polymorphism (G to C) in the promoter region of the PEMT has been demonstrated to contribute to development of organ dysfunction in conjunction with a low-choline diet.

Cardiovascular disease and atherosclerosis PEMT modulates levels of blood plasma homocysteine, which is either secreted or converted to methionine or cysteine. High levels of homocysteine are linked to cardiovascular disease and atherosclerosis, particularly coronary artery disease. PEMT deficiency prevents atherosclerosis in mice fed high-fat, high-cholesterol diets. This is largely a result of lower levels of VLDL lipids in the PEMT-deficient mice. Furthermore, the decreased lipid (PC) content in VLDLs causes changes in lipoprotein structure which allow them to be cleared more rapidly in the PEMT-deficient mice.

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Illustrations

Worked examples

Example 1 — a first encounter with Phosphatidylethanolamine N-methyltransferase

Start with the simplest possible case. Write down what Phosphatidylethanolamine N-methyltransferase claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Phosphatidylethanolamine N-methyltransferase before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Phosphatidylethanolamine N-methyltransferase ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Phosphatidylethanolamine N-methyltransferase

In research: Phosphatidylethanolamine N-methyltransferase appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Phosphatidylethanolamine N-methyltransferase in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Phosphatidylethanolamine N-methyltransferase is common in secondary-school and first-year university syllabi. It links to neighbouring topics EC 2.1.1, Enzymes of unknown structure, Genes on human chromosome 17, so understanding it makes those chapters shorter.
In everyday life: Look for Phosphatidylethanolamine N-methyltransferase outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Phosphatidylethanolamine N-methyltransferase in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Phosphatidylethanolamine N-methyltransferase means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Phosphatidylethanolamine N-methyltransferase out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Phosphatidylethanolamine N-methyltransferase in simple terms?

Why does Phosphatidylethanolamine N-methyltransferase matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Phosphatidylethanolamine N-methyltransferase?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Phosphatidylethanolamine N-methyltransferase.