These are intracellular aminotransferases that get released out of the cells when there is liver pathology. Melinda Samaniego. Posted 7 years ago. is there a video that is just about the urea cycle?

i would like to know everything there is to know about the urea cycle in detail. Posted 5 years ago. In carbohydrate deprivation, if there was exogenous fat and protein ingestion without carbohydrate, how would excess amino acids be handled?

Posted 4 years ago. Direct link to ada. Gluconeogenesis since the need for glucose is acute. But her vid also shows that not all aa contribute to gluconeogenesis. Only glucogenic aa do.

Ariel Tan. The liver uses AA for protein synthesis, or sends it to other tissues in the body for protein synthesis. Does this mean only "excess" AA is used for metabolism? The body will preferentially use AA for protein synthesis unless there's a significant surplus? Or is the body always using a little bit for energy?

What triggers AA metabolism then? How does the body know when AAs are "in excess"? Posted 10 months ago. Could Khan make a video specifically about the Urea Cycle?

I've been using Khan for Biochemistry. Candace Lei. Do we have to memorize the process of generation of ketone bodies from keto acid for MCAT? Julian Burton-Pierce. At Video transcript - [Instructor] In this video, I wanna provide you with a crash course overview of amino acid metabolism.

And, specifically, I wanna focus on the catabolism of amino acids and how that catabolism allows us to produce ATP inside of ourselves. Now, compared to carbohydrate catabolism and fatty acid catabolism, recall the pathways of glycolysis and fatty acid oxidation.

So that's why I think that amino acid metabolism doesn't usually get its fair share of airtime, compared to processes like glycolysis and fatty acid oxidation.

And to do that, let's go ahead and follow what happens to amino acids in the fed, as well as the fasted states of our body. Now, fed refers to our body's state right after, immediately after eating a meal.

And, remember, that in terms of hormones, the hormone that's going to be elevated is going to be insulin, which is elevated in response to higher blood glucose levels, immediately following a meal, and levels of the hormone glucagon are going to be decreased.

Now, of course, this is going to be opposite several hours after a meal, which we called the fasted state, in which the levels of insulin will be decreased and, of course, in response to low blood glucose levels, the levels of glucagon in our body will start to rise along with a couple of other hormones as well.

But these are the two, or two at least, big hormones that regulate the bulk of metabolism in our body. Now, starting with the fed state, let's start at the beginning of this story. Recall that we ingest proteins from our food and those proteins are broken down into amino acids inside of our small intestine.

And just as a side note, you might hear the terms essential and non-essential amino acids used, especially in medical literature. And what this simply refers to is that essential amino acids are those amino acids, of the 20 that we know of, that our body cannot synthesize and so we must, somehow, get these in our diet.

Whereas non-essential amino acids can be actually synthesized in our body and we don't need them as part of our diet. But, getting back to these amino acids, once they're broken down in the small intestine, they travel via the blood stream directly to the liver, just like glucose.

Now, once the amino acids have made it to the liver, several things can happen. The liver can use these amino acids directly for protein synthesis. And, of course, recall that the storage, the ultimate storage forms of these two molecules are gonna be glycogen, in the case of glucose, which is stored in the liver mainly, and, for fatty acids, we store these as triacylglycerides in our adipose tissue.

So how did this conversion from amino acids to glucose and fatty acids happen, you might ask? Well, remember that the precursor for glucose, or I should say precursors, can be pyruvate as well as oxaloacetate. And, for fatty acids, the main precursor for fatty acid synthesis is the molecule acetyl-CoA.

And, as a relevant side note, I wanna point out that acetyl-CoA happens to be in equilibrium with another molecule in the cell called acetoacetyl-CoA. And oxaloacetate if you remember is in equilibrium with a lot of the intermediates of the Krebs cycle.

So I'm gonna abbreviate here as intermediates of Krebs cycle, and there are numerous molecules with numerous names that I won't mention here, but just so that you get the big picture.

Now the key point here is that amino acids, specifically the carbon backbone of these amino acid molecules can be interconverted and metabolized directly into the molecules in the precursor molecules that I've listed here for fatty acids and glucose.

So they can be converted directly into pyruvate, into oxaloacetate, as well as intermediates of the Krebs cycle, acetyl-CoA, as well as acetoacetyl-CoA.

Now another classification that you might hear with regard to amino acids is whether an amino acid is so-called a ketogenic amino acid or whether it is a glucogenic amino acid, and that simply refers to whether the carbon backbone of these amino acid molecules feeds into the precursor molecules for glucose synthesis or whether it feeds into the precursor molecules for fatty acid synthesis.

So in this case, ketogenic amino acids are converted to acetyl-CoA or acetoacetyl-CoA and ultimately fatty acids, whereas glucogenic amino acids feed into pyruvate, oxaloacetate, or intermediates of the Krebs cycle. Now just as a fun fact, it turns out that there are two amino acids that are exclusively ketogenic and those are lysine and leucine.

So anytime you ingest lysine or leucine, you will definitely be making fatty acids from those amino acids if they're ingested in excess. Of course, other amino acids can actually contribute to glucogenic pathways, and some might even contribute to both, but that's just kind of a fun fact.

Now going back to the journey of our amino acids here, remember that it enters the liver and the liver can either use it for protein synthesis or convert it into other energy storage forms. But it can also send it off, and it can send it off to other tissues such as the muscle, for example, where the muscle can use it for its own protein synthesis.

So other cells will also receive amino acids that are digested that they can use for protein synthesis as well. Now moving on to the fasted state, I'm also gonna put the liver here at kind of the center of our diagram because, remember, the liver is quite a centerpiece when it comes to metabolism.

A lot of things are going on in the liver, and, specifically, in the fasted state, you might recall that fatty acids are being released from adipose tissue and being sent to the liver where they're being oxidized, and all of that ATP is fueling the synthesis of glucose.

And if the person is in a very severe state of starvation, let's say they haven't had a meal for two or three days, we might even be producing ketones as well. Now even though we think of fatty acids as being the main fuel that's being sent to the liver in times of fasting, we can't forget about amino acids, which are released from our tissues, mostly our muscles really, and they're sent via the bloodstream also to the liver.

Now once amino acids have arrived at the liver, the factory house, so to say, for energy production in times of fasting, remember that they can enter a diverse array of metabolic pathways. So I want to remind you in our fed discussion, we talked about glucogenic and ketogenic amino acids.

So in times of fasting, potentially these glucogenic amino acids can contribute to these precursors of gluconeogenesis and help support the production of glucose in times of fasting.

They are distinguished from one another primarily by , appendages to the central carbon atom. Figure 2 Figure Detail In the study of metabolism, a series of biochemical reactions for compound synthesis or degradation is called a pathway. Amino acid synthesis can occur in a variety of ways.

For example, amino acids can be synthesized from precursor molecules by simple steps. Alanine, aspartate, and glutamate are synthesized from keto acids called pyruvate, oxaloacetate, and alpha-ketoglutarate, respectively, after a transamination reaction step.

Similarly, asparagine and glutamine are synthesized from aspartate and glutamate, respectively, by an amidation reaction step. The synthesis of other amino acids requires more steps; between one and thirteen biochemical reactions are necessary to produce the different amino acids from their precursors of the central metabolism Figure 2.

The relative uses of amino acid biosynthetic pathways vary widely among species because different synthesis pathways have evolved to fulfill unique metabolic needs in different organisms. Although some pathways are present in certain organisms, they are absent in others.

Therefore, experimental results about amino acid metabolism that are achieved with model organisms may not always have relevance for the majority of other organisms. Not all the organisms are capable of synthesizing all the amino acids, and many are synthesized by pathways that are present only in certain plants and bacteria.

Mammals, for example, must obtain eight of twenty amino acids from their diets. This requirement leads to a convention that divides amino acids into two categories: essential and nonessential given a certain metabolism.

Because of particular structural features, essential amino acids cannot be synthesized by mammalian enzymes Reeds Nonessential amino acids, therefore, can be synthesized by nearly all organisms.

The loss of the ability to synthesize essential amino acids likely emerged very early in evolution, because this dependence on other organisms for the source of amino acids is common among all eukaryotes, not just those of mammals.

How do certain amino acids become essential for a given organism? Studies in ecology and evolution give some clues. Organisms evolve under environmental constraints, which are dynamic over time.

If an amino acid is available for uptake, the selective pressure to keep intact the genes responsible for that pathway might be lowered, because they would not be constantly expressing these biosynthetic genes.

Without the selective pressure, the biosynthetic routes might be lost or the gene could allow mutations that would lead to a diversification of the enzyme 's function. Following this logic, amino acids that are essential for certain organisms might not be essential for other organisms subjected to different selection pressures.

For example, in , Ishikawa and colleagues completed the genome sequence of the endosymbiont bacteria Buchnera , and in it they found the genes for the biosynthetic pathways necessary for the synthesizing essential amino acids for its symbiotic host, the aphid.

Interestingly, those genes for the synthesis of its "nonessential" amino acids are almost completely missing Shigenobu et al. In this way, Buchnera provides the host with some amino acids and obtains the other amino acids from the host Baumann ; Pal et al.

Free-living bacteria synthesize tryptophan Trp , which is an essential amino acid for mammals, some plants, and lower eukaryotes. The Trp synthesis pathway appears to be highly conserved, and the enzymes needed to synthesize tryptophan are widely distributed across the three domains of life.

This pathway is one of three that compose aromatic amino acids from chorismate Figure 2, red pathway. The other amino acids are phenylalanine and tyrosine. Trp biosynthetic enzymes are widely distributed across the three domains of life Xie et al.

The genes that code for the enzymes in this pathway likely evolved once, and they did so more recently than those for other amino acid synthesis pathways. As another point of distinction, the Trp pathway is the most biochemically expensive of the amino acid pathways, and for this reason it is expected to be tightly regulated.

To date, scientists have discovered six different biosynthetic pathways in different organisms that synthesize lysine. These pathways can be grouped into the diaminopimelic acid DAP and aminoadipic acid AAA pathways Figure 2, dark blue. The DAP pathway synthesizes lysine Lys from aspartate and pyruvate.

Most bacteria, some archaea , fungi, algae, and plants use the DAP pathways. On the other hand, the AAA pathways synthesize Lys from alpha-ketoglutarate and acetyl coenzyme A. Most fungi, some algae, and some archaea use this route. Why do we observe this diversity, and why does it occur particularly for Lys synthesis?

Interestingly, the DAP pathways retain duplicated genes from the biosynthesis of arginine, whereas the AAA pathways retain duplicated genes from leucine biosynthesis Figure 2 , indicating that each of the pathways experienced at least one duplication event during evolution Hernandez-Montes et al.

Fani and coworkers performed a comparative analysis of the synthesis enzyme sequences and their phylogenetic distribution that suggested that the synthesis of leucine, lysine, and arginine were initially carried out with the same set of versatile enzymes.

Over the course of time came a series of gene duplication events and enzyme specializations that gave rise to the unambiguous pathways we know today. Which of the pathways appeared earlier is still a source of query and debate.

To support this hypothesis, there is evidence from a fascinating archaea, Pyrococcus horikoshii. This organism can synthesize leucine, lysine, and arginine, yet its genome contains only genes for one pathway.

Such a gap indicates that P. horikoshii has a mechanism similar to the ancestral one: versatile enzymes.

Biochemical experiments are needed to further support the idea that these enzymes can use multiple substrates and to rule out the possibility that amino acid synthesis in this organism does not arise from enzymes yet unidentified.

Selenocysteine SeC Bock is a genetically encoded amino acid not present in all organisms. Scientists have identified SeC in several archaeal, bacterial, and eukaryotic species even mammals. When present, SeC is usually confined to active sites of proteins involved in reduction-oxidation redox reactions.

It is highly reactive and has catalytic advantages over cysteine, but this high reactivity is undermined by its potential to cause cell damage if free in the cytoplasm. Hence, it is too dangerous, and no pool of free SeC is available.

How, then, is this amino acid synthesized for use in protein synthesis? The answer demonstrates the versatility of synthesis strategies deployed by organisms forced to cope with singularities. The synthesis of SeC is carried out directly on the tRNA substrate before being used in protein synthesis.

First, SeC-specific tRNA tRNA sec is charged with serine via seril-tRNA synthetase, which acts in a somehow promiscuous fashion, serilating either tRNA ser or tRNA sec.

Then, another enzyme modifies Ser to SeC by substituting the OH radical with SeH, using selenophosphate as the selenium donor Figure 2, pink pathway. This synthesis is a form of a trick to avoid the existence of a free pool of SeC while still maintaining a source of SeC-tRNA sec needed for protein synthesis.

Strictly speaking, this mechanism is not an actual synthesis of amino acids, but rather a synthesis of aminoacetylated-tRNAs. However, this technique involving tRNA directly is not exclusive to SeC, and similar mechanisms dependent on tRNA have been described for asparagine, glutamine, and cysteine.

Owing to its appearance of SeC across all three domains of life, scientists wonder if it is an ancestral mechanism for amino acid biosynthesis or simply a coincidence of selection pressures. In , Horowitz proposed the first accepted model for metabolic pathway evolution Horowitz Called the retrograde model, it states that after an enzyme consumes all its substrate available, another enzyme capable of producing the aforementioned substrate is required, so the last enzyme evolved to the preceding one by a gene duplication and selection mechanism.

In other words, enzymes evolve from others with similar substrate specificity, and the substrate of the last enzyme is the product of the preceding one. Also, the active site must bind both the substrate and the product. This model became very popular, but as more genes have been sequenced and more phylogenetic analyses performed, this mechanism has become less seemingly plausible and therefore unpopular.

An alternative model, the patchwork assembly model, proposes that ancestral enzymes were generalists, so they could bind a number of substrates to carry out the same type of reaction.

Gene duplication events followed by evolutionary divergence would result in enzymes with high affinity and specificity for a substrate. In other words, enzymes are recruited from others with the same type of chemical reaction. Whole genome analysis of Escherichia coli supports the patchwork evolution model Teichmann et al.

Duplication of whole pathways does not occur very often; nevertheless, examples include tryptophan to synthesize paraminobenzoate and histidine to synthesize nucleotides biosynthesis, as well as lysine, arginine, and leucine biosynthesis see aforementioned example.

Amino acids are one of the first organic molecules to appear on Earth. As the building blocks of proteins, amino acids are linked to almost every life process, but they also have key roles as precursor compounds in many physiological processes. These processes include intermediary metabolism connections between carbohydrates and lipids , signal transduction , and neurotransmission.

Recent years have seen great advances in understanding amino acid evolution, yet many questions on the subject of amino acid synthesis remain. What was the order of appearance of amino acids over evolutionary history?

How many amino acids are used in protein synthesis today? How many were present when life began? Were there initially more than twenty used for building blocks, but intense selective process streamlined them down to twenty? Conversely, was the initial set much less than twenty, and did new amino acids successively emerge over time to fit into the protein synthesis repertoire?

What are the tempo and mode of amino acid pathway evolution? These questions are waiting to be tackled — with old or new hypotheses, conceptual tools, and methodological tools — and are ripe for a new generation of scientists.

Scientists now recognize twenty-two amino acids as the building blocks of proteins: the twenty common ones and two more, selenocysteine and pyrrolysine. Amino acids have several functions. Their primary function is to act as the monomer unit in protein synthesis. They can also be used as substrates for biosynthetic reactions; the nucleotide bases and a number of hormones and neurotransmitters are derived from amino acids.

Amino acids can be synthesized from glycolytic or Krebs cycle intermediates. The essential amino acids, those that are needed in the diet, require more steps to be synthesized.

Some amino acids need to be synthesized when charged onto their corresponding tRNAs. We have discussed only two biosynthetic routes: the Trp pathway, which appears to have evolved only once, and the Lys pathway, which seems to have evolved independently in different lineages.

Prevailing evidence suggests that metabolic pathways themselves seem to be evolving following the patchwork assembly model, which proposes that pathways originated through the recruitment of generalist enzymes that could react with a wide range of substrates.

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