science

Nucleoside-diphosphate kinase

Nucleoside-diphosphate kinase 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 Nucleoside-diphosphate kinase rather than just read about it. In short: Nucleoside-diphosphate kinases (NDPKs, also NDP kinase, (poly)nucleotide kinases and nucleoside diphosphokinases) are enzymes that catalyze the exchange of terminal phosphate between different nucleoside diphosphates (NDP) and triphosphates (NTP) in a reversible manner to produce nucleotide triphosphates. Many NDP serve as acceptor while NTP are donors of phosphate group.

Key takeaways

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

Reference excerpt

Nucleoside-diphosphate kinases (NDPKs, also NDP kinase, (poly)nucleotide kinases and nucleoside diphosphokinases) are enzymes that catalyze the exchange of terminal phosphate between different nucleoside diphosphates (NDP) and triphosphates (NTP) in a reversible manner to produce nucleotide triphosphates. Many NDP serve as acceptor while NTP are donors of phosphate group. The general reaction via ping-pong mechanism is as follows: XDP + YTP ←→ XTP + YDP (X and Y each represent different nitrogenous base). NDPK activities maintain an equilibrium between the concentrations of different nucleoside triphosphates such as, for example, when guanosine triphosphate (GTP) produced in the citric acid (Krebs) cycle is converted to adenosine triphosphate (ATP). Other activities include cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor, endocytosis, and gene expression.

Structure NDPK are homohexameric proteins made up of monomers approximately 152 amino acids long with a theoretical weight of 17.17KDa. The complex is found in mitochondria and in the soluble cytoplasm of cells.

Function NDPK are found in all cells, displaying not much specificity towards the types of nucleoside bases and are capable of accepting nucleotides and deoxyribonucleotides as substrates or donors. Therefore, NDPK is the source of RNA and DNA precursors, except ATP. NDPK utilize specific enzyme kinetics for multi-substrate reaction, namely ping-pong mechanism. A ping-pong mechanism integrates phosphorylation of a histidine residue by transferring terminal phosphate group (γ-phosphate) from ATP to NDP β-phosphate in order to produce a NTP, and NDPK catalyzes such reversible reactions. NTP phosphorylates a histidine, which in turn phosphorylates NDP. NDPK are involved in the synthesis of nucleoside triphosphates (NTP), such as guanosine triphosphate (GTP), cytidine triphosphate (CTP) and uridine triphosphate (UTP), thymidine triphosphate (TTP).

Behind this apparently simple reaction is a multistep mechanism. The key steps of transphosphorylation are as follows:

NDPK binds to a NTP1 A phosphoryl group from NTP1 is transferred to His in active site of NDPK Phosphoenzyme intermediate is formed Initially bound NDP1 is released from NDPK bringing in new NDP2 Phosphoryl group is transferred from NDPK-His to NDP2 or dNDP2, creating a bound NTP2 NDPK releases the new NTP2 Each step is part of a reversible process, such that the multistep equilibrium is of the following form.

NDPK + NTP ↔ NDPK~NTP ↔ NDPK-P~NDP ↔ NDPK-P + NDP NDPK's roles in these NTPs differ; generally, kinases bring in NTPs for nucleic acid synthesis. CTP is provided for lipid synthesis, UTP for polysaccharide synthesis while GTP is used for protein elongation and signal transduction. During cAMP-mediated signal transduction, NDPK is responsible for phosphorylating GDP released from G proteins activated from receptor binding; once ATP donates a phosphate group via activity of NDPK, GTP is consecutively bound. Increased activity of membrane-associated NDPK yields cAMP synthesis. NDPK controls K+ channels, G proteins, cell secretion, cellular energy production, and UTP synthesis.

Regulation

Inhibition by AMPK NDPK usually consumes ATP, the most abundant cellular nucleotide, and stores the nucleotides. However, consumption of ATP would definitely influence the cellular energy balance, which brings upon the regulation of AMP-activated protein kinase (AMPK). AMPK acts as the energy sensor and regulates ATP pathways by turning the generating pathways or not. Because of such activity, AMPK could directly inhibit NDPK through phosphorylation. To be more specific, NDPK supports the production of nucleotides in high-energy and low-stress cellular states. However, this can only happen when AMPK is inactivated because low-stress cellular states of ATP triggers the activation of AMPK, which eventually decreases NDPK activity by phosphorylating serine residues.

Prokaryotic systems In most prokaryotes, the NDPK enzyme is tetrameric. It has been reported in a number of pathogens. NDPK function has been studied in Escherichia coli, Bacillus subtilis, Salmonella typhimurium, Micrococcus luteus, and Myxococcus xanthus. Prokaryotic NDPK forms a functional homotetramer. Nucleoside diphosphate kinase activity involves the transfer of the γ-phosphate of nucleoside triphosphate (NTP) to nucleoside diphosphate (NDP), where N1 and N2 can be ribo- or deoxyribonucleosides. This is done via a high energy phosphohistidine intermediate. Besides involvement in the synthesis of pyrimidine nucleotides, prokaryotic NDPK is also involved in several metabolism cycles. NDPK has also been discovered to act as a protein histidine kinase, which involves a reversible histidine phosphorylation as a well-known regulatory signal. However, in most prokaryotes, NDPK expression levels are involved in the cell growth, development and differentiation of the organism, especially bacteria.

(p)ppGpp metabolism In the (p)ppGpp biosynthesis cycle, NDPK serves an important role. When there is an absence of a charged tRNA in the A site of a ribosome, the ribosome will stall and trigger the synthesis of the guanosine pentaphosphate ((p)ppGpp) molecule. (p)ppGpp biosynthesis is a part of the purine metabolism pathway and coordinates a series of cellular activities in response to nutritional abundances. Synthesis of (p)ppGpp is triggered by carbon starvation, or the lack of carbon in the cell's environment, and causes the protein SpoT to activate. SpoT works in conjunction with NDPK and both serve as essential enzymes in the (p)ppGpp biosynthesis cycle. NDPK synthesizes the formation of GDP from GTP via dephosphorylation.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Nucleoside-diphosphate kinase

Start with the simplest possible case. Write down what Nucleoside-diphosphate kinase 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 Nucleoside-diphosphate kinase 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 Nucleoside-diphosphate kinase 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 Nucleoside-diphosphate kinase

In research: Nucleoside-diphosphate kinase 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 Nucleoside-diphosphate kinase 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: Nucleoside-diphosphate kinase is common in secondary-school and first-year university syllabi. It links to neighbouring topics EC 2.7.4, Enzymes, so understanding it makes those chapters shorter.
In everyday life: Look for Nucleoside-diphosphate kinase 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.

Ask Teacher Smith questions about this articleOpens your AI tutor with a question about “Nucleoside-diphosphate kinase” →

Affiliate

Preply — study more efficiently by working with a personal tutor. 50% off.

How to study Nucleoside-diphosphate kinase in 20 minutes

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

Frequently asked questions

What is Nucleoside-diphosphate kinase in simple terms?

Why does Nucleoside-diphosphate kinase 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 Nucleoside-diphosphate kinase?

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 Nucleoside-diphosphate kinase.