biology

GOT2

GOT2 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 GOT2 rather than just read about it. In short: Aspartate aminotransferase, mitochondrial, is an enzyme that in humans is encoded by the GOT2 gene. Glutamic–oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and inner-membrane mitochondrial forms, GOT1 and GOT2, respectively.

Key takeaways

GOT2 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect GOT2 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of GOT2 from memory before moving on to harder problems.

Reference excerpt

Aspartate aminotransferase, mitochondrial, is an enzyme that in humans is encoded by the GOT2 gene. Glutamic–oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and inner-membrane mitochondrial forms, GOT1 and GOT2, respectively. GOT plays a role in amino acid metabolism and the urea and tricarboxylic acid cycle. Also, GOT2 is a major participant in the malate–aspartate shuttle, which is a passage from the cytosol to the mitochondria. The two enzymes are homodimeric and show close homology. GOT2 has been seen to have a role in cell proliferation, especially in terms of tumor growth.

Structure GOT2 is a dimer containing two identical subunits that hold overlapping subunit regions. The top and sides of the enzyme are made up of helices, while the bottom is formed by strands of beta sheets and extended hairpin loops. The subunit itself can be categorized into four different parts: a large domain, which binds pyridoxal-P, a small domain, an NH2-terminal arm, and a bridge across two domains, which is formed by residues 48–75 and 301–358. Virtually ubiquitous in eukaryotic cells, GOT2 nucleic acid and protein sequences are highly conserved, and its 5′ regulatory regions in genomic DNA resemble those of typical house-keeping genes in that, e.g., they lack a TATA box. The GOT2 gene is also located on 16q21 and has an exon count of 10.

Function In order to produce the energy needed for everyday activities, our body needs to go through the process of glycolysis, which breaks down glucose into pyruvate. In this pathway, one very important part is the reduction of NAD+ to NADH and then the rapid oxidation of NADH back into NAD+. The oxidation phase mainly occurs in the mitochondria as part of the electron transport chain, but the transfer of NADH into the mitochondria from the cytosol is impossible, due to the impermeability of the inner mitochondrial membrane to NADH. Therefore, the malate-aspartate shuttle is needed to transfer reducing equivalents across the mitochondrial membrane for energy production. GOT2 and another enzyme, MDH, are essential for the functioning of the shuttle. GOT2 converts oxaloacetate into aspartate by transamination. This aspartate as well as alpha-ketoglutarate return into the cytosol, which is then converted back to oxaloacetate and glutamate, respectively. Another function of GOT2 is that it is believed to transaminate kynurenine into kynurenic acid (KYNA) in the brain. The KYNA made by the GOT2 is thought to be an important factor in brain pathology. It is suggested that KYNA synthesized by GOT2 could constitute a common, and mechanistically relevant, feature of the neurotoxicity caused by mitochondrial poisons, such as rotenone, malonate, 1-methyl-4-phenylpyridinium, and 3-nitropropionic acid.

Clinical Significance In nearly all cancer cells, glycolysis has been seen to be highly elevated to meet their increased energy, biosynthesis, and redox needs. Therefore, the malate-aspartate shuttle promotes the net transfer of cytosolic NADH into mitochondria to ensure a high rate of glycolysis in diverse cancer cell lines. In a study completed in 2008, inhibiting the malate-aspartate shuttle was found to impair the glycolysis process and essentially decreased breast adenocarcinoma cell proliferation. Furthermore, knocking down GOT2 and GOT1 has also been reported to inhibit cell proliferation and colony formation in pancreatic cancer cell lines, suggesting that the GOT enzyme is essential for maintaining a high rate of glycolysis to support rapid tumor cell growth. Also, both glucose and glutamine increase GOT2 3K acetylation in PANC-1 cells and that GOT2 3K acetylation plays a critical role in coordinating glucose and glutamine uptake to provide energy and support cell proliferation and tumor growth. This implies that inhibiting GOT2 3K acetylation may merit exploration as a therapeutic agent especially for pancreatic cancer. Mutations in this gene have been associated with an early onset infantile encephalopathy.

Interactions GOT2 has been seen to interact with:

oxaloacetate kynurenine aspartate alpha-ketoglutarate

Interactive pathway map Click on genes, proteins and metabolites below to link to respective articles.

References

Illustrations

Worked examples

Example 1 — a first encounter with GOT2

Start with the simplest possible case. Write down what GOT2 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 GOT2 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 GOT2 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 GOT2

In research: GOT2 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 GOT2 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: GOT2 is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 16, Mitochondrial proteins, so understanding it makes those chapters shorter.
In everyday life: Look for GOT2 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 GOT2 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what GOT2 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 GOT2 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is GOT2 in simple terms?

Why does GOT2 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 GOT2?

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 GOT2.