science

Mevalonate pathway

Mevalonate pathway is a science 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 Mevalonate pathway rather than just read about it. In short: The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway, is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are used to make isoprenoids, a diverse class of over 30,000 biomolecules such as cholesterol, vitamin K…

Key takeaways

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

Reference excerpt

The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway, is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are used to make isoprenoids, a diverse class of over 30,000 biomolecules such as cholesterol, vitamin K, coenzyme Q10, and all steroid hormones. The mevalonate pathway begins with acetyl-CoA and ends with the production of IPP and DMAPP. It is best known as the target of statins, a class of cholesterol lowering drugs. Statins inhibit HMG-CoA reductase within the mevalonate pathway.

Upper mevalonate pathway The mevalonate pathway of eukaryotes, archaea, and eubacteria all begin the same way. The sole carbon feed stock of the pathway is acetyl-CoA. The first step condenses two acetyl-CoA molecules to yield acetoacetyl-CoA. This is followed by a second condensation to form HMG-CoA (3-hydroxy-3- methyl-glutaryl-CoA). Reduction of HMG-CoA yields (R)-mevalonate. These first 3 enzymatic steps are called the upper mevalonate pathway.

Lower mevalonate pathway The lower mevalonate pathway which converts (R)-mevalonate into IPP and DMAPP has 3 variants. In eukaryotes, mevalonate is phosphorylated twice in the 5-OH position, then decarboxylated to yield IPP. In some archaea such as Haloferax volcanii, mevalonate is phosphorylated once in the 5-OH position, decarboxylated to yield isopentenyl phosphate (IP), and finally phosphorylated again to yield IPP (Archaeal Mevalonate Pathway I). A third mevalonate pathway variant found in Thermoplasma acidophilum, phosphorylates mevalonate at the 3-OH position followed by phosphorylation at the 5-OH position. The resulting metabolite, mevalonate-3,5-bisphosphate, is decarboxylated to IP, and finally phosphorylated to yield IPP (Archaeal Mevalonate Pathway II).

Regulation and feedback Several key enzymes can be activated through DNA transcriptional regulation on activation of SREBP (sterol regulatory element-binding protein-1 and -2). This intracellular sensor detects low cholesterol levels and stimulates endogenous production by the HMG-CoA reductase pathway, as well as increasing lipoprotein uptake by up-regulating the LDL-receptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation.

Pharmacology A number of drugs target the mevalonate pathway:

Statins (used to decrease cholesterol levels); Bisphosphonates (used to treat various bone-degenerative diseases such as osteoporosis)

Diseases A number of diseases affect the mevalonate pathway:

Mevalonate Kinase Deficiency Mevalonic Aciduria Hyperimmunoglobulinemia D Syndrome (HIDS).

Alternative pathway Plants, most bacteria, and some protozoa such as malaria parasites have the ability to produce isoprenoids using an alternative pathway called the methylerythritol phosphate (MEP) or non-mevalonate pathway. The output of both the mevalonate pathway and the MEP pathway are the same, IPP and DMAPP; however, the enzymatic reactions to convert acetyl-CoA into IPP are entirely different. Interaction between the two metabolic pathways can be studied by using 13C-glucose isotopomers. In higher plants, the MEP pathway operates in plastids while the mevalonate pathway operates in the cytosol. Examples of bacteria that contain the MEP pathway include Escherichia coli and pathogens such as Mycobacterium tuberculosis.

Enzymatic reactions

References

External links Rensselaer Polytechnic Institute page on cholesterol synthesis (including regulation)

Illustrations

Worked examples

Example 1 — a first encounter with Mevalonate pathway

Start with the simplest possible case. Write down what Mevalonate pathway claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, 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 Mevalonate pathway 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 Mevalonate pathway 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 Mevalonate pathway

In research: Mevalonate pathway appears in science 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 Mevalonate pathway 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: Mevalonate pathway is common in secondary-school and first-year university syllabi. It links to neighbouring topics Metabolic pathways, so understanding it makes those chapters shorter.
In everyday life: Look for Mevalonate pathway 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 Mevalonate pathway in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Mevalonate pathway 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 Mevalonate pathway out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Mevalonate pathway in simple terms?

Why does Mevalonate pathway matter?

Because it connects several science 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 Mevalonate pathway?

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 Mevalonate pathway.