Bom Bong 1 second ago This is very cut down. The full process is called the Cahill cycle: 1) pyruvate combines with glutamate to form alanine and a-KG. 2) Alanine is transported to the liver 3)in the liver reverse of step 1. 4) Pyruvate is transformed into glucose via gluconeogeneia in the liver and the glucose is transported to the muscles 5)glutamate undergoes oxidative deamination(In mitochondrial only) giving a-KG and ammonia 6) ammonia enter urea cycle NET RXN: Alanine to liver( form of ammonia) and glucose back to muscle( to generate more ATP via glycolysis) . Ammonia is removed from the muscle successfully
Awesome explanation just ONE MISTAKE you are missing the intermediate steps. The the ammonia actually combines with a-KG via a transamination reaction to from glutamate + a-ketoacid. The glutamate produced will then undergo a transamination reaction with pyruvate via alanine aminotransaminase (ALT) to reform a-KG and Alanine. Alanine is then transferred to the liver where it undergoes another transamination reaction with a-KG to form pyruvate and Glutamate. Everything else is correct. I got lost when you said NH3 combines with pyruvate to make glutamate because glutamate is made by transamination reaction between a-KG and NH3 (containing amino acids) . Essentially all we are doing here is moving the ammonia around so that we can make urea in the liver.
I agree with you, and once the glutammate is made by transamination into the liver, then it's deaminated by glutamate dehydrogenase to release NH4+ that can enter into the urea cycle; or it can also be transansaminated (transferring the NH3 to the oxaloacetate) to form aspartate that can also enter the urea cycle.
I've relied on your videos so heavily for guidance throughout my biochemistry curriculum and have watched so many of your videos that apparently, as pointed out by my buddy, when I explain concepts to underclassmen my speech automatically codeswitches to the Andrey Kopot dialect, lmaooo. With much respect from New Orleans, LA, USA.
Haha I agree I am a TA for an undergraduate biochemistry course and whenever I am teaching in my discussion class I frequently catch my self using the AK lectures dialect.
Wait, why is Glutamate produced from Pyruvate and NH4? NH4+Pyruvate creates Alanine only? a Ketoglutarate is used for Glutamate, or am I missing something here?
I'm not sure the diagram was drawn correctly. You're correct about pyruvate being converted into alanine. However, most times, the amino group comes from the deamination of glutamate into a-ketoglutarate rather than a free ammonium as he had drawn. The reverse of this occurs in the liver and the NH4 is given up from the glutamate.
I thought the same.... how did you get from pyruvate to glutamate? And where did you get nh2-.- Alanin + alpha ketoglut = pyruvate and glutamate - there is no "free " ammonium
When energy is needed, muscles degrade amino acids which result in ammonium ions being present. Ammonium is converted into Glutamate. Now a transamination occurs... Glutamate's amino group and Pyruvate's carbonyl group swap, and this ends up giving us α-ketoglutarate and Alanine. I think the diagram was drawn correctly, its just an overall picture.
The NH4 comes from the branched amino acids thanks to glutamate, which acts as a transporter of the group; it then transfers the NH2 onto pyruvate to obtain Alanine. Alanine is transported to the liver and donates it NH2 group to ketoglutarate to obtain pyruvate (and then glucose) but most importantly we also obtain glutamate, which is deaminated to free NH4 in the hepatocytes, where it will be metabolised via the urea cycle. The diagram may be a bit confusing in the pyruvate->alanine part but just keep in mind that glutamate is not actually a product of pyruvate, but just a co-reagent
Atleast one should consider liking sir' s videos, look how awesome sir' s videos are and how much effort it takes into making these videos. It will maybe make youtube flash sir' s videos more and it will be good for everybody.
Glycogen in muscle break down into glucose 1 phosphate(not into glucose).... And then it make G6P... Pyruvate.... Nice lecture... I'm 1st year medical student in Bangladesh.....i love all videos of ak Lecture....
For the latter pathway you metioned that involves the glutamine synthetase enzyme, our professor is having us learn this pathway and I have a question about the different shuttles that transport molecules across the membrane between the matrix and the cytosol within the liver. As I understand it, there are at least two antiporters that are used in conjunction with the urea cycle, the Malate/𝞪-ketoglutarate antiporter and the Glutamate/Aspartate antiporter. I understand that Glutamine is being shuttled into the liver to release the two ammonium ions to be used in urea formation, however, what is the purpose of a glutamate/aspartate shuttle if it's glutamine that's being shuttled to the liver and not glutamate? Is glutamate also somehow transported to the liver to release ammonium for the urea cycle, or are these antiporters different form how I understand them?
The glutamate produced from the deamination of glutamine in the liver mitochondria needs to be transported back to the cytosol for further utilization. This is where the glutamate/aspartate antiporter is involved. It exchanges glutamate (generated from the deamination of glutamine) for aspartate, allowing the cytosolic glutamate to be used for various purposes. The aspartate generated in the cytosol through this exchange can participate in the urea cycle as well. Aspartate is involved in the synthesis of argininosuccinate, an intermediate in the urea cycle. So, to summarize, the glutamate/aspartate antiporter is not directly involved in shuttling glutamine to the liver for ammonia release. Its primary role is to transport glutamate (derived from the deamination of glutamine) back to the cytosol and exchange it for aspartate, which has various metabolic roles, including its involvement in the urea cycle.
Once in the liver, does the reansamination back to Glutamate and Pyruvate occur in the cytoplasm or the mitochondrial matrix of the cell? The deamination of Glutamate occurrs in the matrix (since it's toxic for the cell and because the Urea cycle's first phase is there) so if Glu is transaminated in the cytoplasm, does it diffues into the matrix afterwards?
Glutamate / pyruvate transamination takes place in the CYTOPLASM , a reaction catalyzed by the enzyme (ALT) , as pyruvate is the end product of glycolysis , which takes place in the cytoplasm !While Glutamate / oxaloacetate transamination takes place in the MITOCHONDRIA , a reaction catalyzed by the enzyme (AST) , as oxaloacetate is an intermediate of Kreb's cycle , which takes place in the mitochondrial matrix !
so glad you're back :))) can you tell what will be the next subject after biochem if any? I hope some advanced human physiology or something usefull for med students but whatever it is it will be great for sure!!
Thanks! I haven't decided yet but something that will definitely be helpful to medical students. Some sort of combination of physiology/pathophysiology.
Branched chain amino acids (Ile, Leu, Val) cannot be taken directly to the liver to be transaminated -- if this was the case, the glucose-alanine cycle would serve no purpose. To clarify, non-branched amino acids can be transaminated directly in the liver but branched ones cannot b/c the liver doesn't have the necessary enzymes (aminotransferases) in order to metabolize these molecules.
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Bom Bong
1 second ago
This is very cut down. The full process is called the Cahill cycle: 1) pyruvate combines with glutamate to form alanine and a-KG. 2) Alanine is transported to the liver 3)in the liver reverse of step 1. 4) Pyruvate is transformed into glucose via gluconeogeneia in the liver and the glucose is transported to the muscles 5)glutamate undergoes oxidative deamination(In mitochondrial only) giving a-KG and ammonia 6) ammonia enter urea cycle
NET RXN: Alanine to liver( form of ammonia) and glucose back to muscle( to generate more ATP via glycolysis) . Ammonia is removed from the muscle successfully
Awesome explanation just ONE MISTAKE you are missing the intermediate steps. The the ammonia actually combines with a-KG via a transamination reaction to from glutamate + a-ketoacid. The glutamate produced will then undergo a transamination reaction with pyruvate via alanine aminotransaminase (ALT) to reform a-KG and Alanine. Alanine is then transferred to the liver where it undergoes another transamination reaction with a-KG to form pyruvate and Glutamate. Everything else is correct. I got lost when you said NH3 combines with pyruvate to make glutamate because glutamate is made by transamination reaction between a-KG and NH3 (containing amino acids) . Essentially all we are doing here is moving the ammonia around so that we can make urea in the liver.
Pa Konnen 👍🏻
I agree with you, and once the glutammate is made by transamination into the liver, then it's deaminated by glutamate dehydrogenase to release NH4+ that can enter into the urea cycle; or it can also be transansaminated (transferring the NH3 to the oxaloacetate) to form aspartate that can also enter the urea cycle.
Stupid question perhaps, but what happens to the alpha-ketoacid that is formed?
@@user-oz9oo3qw4n I'm late, but have you found out the answer?
@@adith520 it is used to form glutamate back.. by receiving nh3 from amino acid breakdown..
very nice & analytic lectures
GOD BLESS YOU
great motivation for working out. glad you're back
sweet! :)
So very clear, can’t thank you enough sir!
Thanks! I was finally able to put it altogether once I watched this video, you the man.
I've relied on your videos so heavily for guidance throughout my biochemistry curriculum and have watched so many of your videos that apparently, as pointed out by my buddy, when I explain concepts to underclassmen my speech automatically codeswitches to the Andrey Kopot dialect, lmaooo.
With much respect from New Orleans, LA, USA.
Thats hilarious James! Awesome to hear though, glad to see they're helping you
Haha I agree I am a TA for an undergraduate biochemistry course and whenever I am teaching in my discussion class I frequently catch my self using the AK lectures dialect.
This is simply amazing thankyou!♥️
a great video to explain the overview. thank you very much
Wait, why is Glutamate produced from Pyruvate and NH4? NH4+Pyruvate creates Alanine only? a Ketoglutarate is used for Glutamate, or am I missing something here?
I'm not sure the diagram was drawn correctly. You're correct about pyruvate being converted into alanine. However, most times, the amino group comes from the deamination of glutamate into a-ketoglutarate rather than a free ammonium as he had drawn. The reverse of this occurs in the liver and the NH4 is given up from the glutamate.
I thought the same.... how did you get from pyruvate to glutamate? And where did you get nh2-.-
Alanin + alpha ketoglut = pyruvate and glutamate - there is no "free " ammonium
When energy is needed, muscles degrade amino acids which result in ammonium ions being present. Ammonium is converted into Glutamate. Now a transamination occurs... Glutamate's amino group and Pyruvate's carbonyl group swap, and this ends up giving us α-ketoglutarate and Alanine. I think the diagram was drawn correctly, its just an overall picture.
The diagram is correct, you can find similar ones in Principles of Biochemistry by Lehninger.
The NH4 comes from the branched amino acids thanks to glutamate, which acts as a transporter of the group; it then transfers the NH2 onto pyruvate to obtain Alanine. Alanine is transported to the liver and donates it NH2 group to ketoglutarate to obtain pyruvate (and then glucose) but most importantly we also obtain glutamate, which is deaminated to free NH4 in the hepatocytes, where it will be metabolised via the urea cycle.
The diagram may be a bit confusing in the pyruvate->alanine part but just keep in mind that glutamate is not actually a product of pyruvate, but just a co-reagent
Atleast one should consider liking sir' s videos, look how awesome sir' s videos are and how much effort it takes into making these videos. It will maybe make youtube flash sir' s videos more and it will be good for everybody.
You are the best man👍
Glycogen in muscle break down into glucose 1 phosphate(not into glucose).... And then it make G6P... Pyruvate....
Nice lecture... I'm 1st year medical student in Bangladesh.....i love all videos of ak Lecture....
Best man ever!!
Very good explanation thanku
Excellent Explanation 👌👍
your explanation is awesome thank you so much, smart and handsome in same time ☺️
it was helpful thank you so much doctor Andrey
You are the best.
Great video
Nice vids. Thank you sir
I trust in your knowledge 👌
if its in a fasted state, how can muscle with GLUT4, insulin dependent, take up glucose from the liver?
S sir... NH4 combine with a kg to form glutamate then glutamate combine with pa to form alanine...
Great work and useful information,,, thanks
You are great thank you so much ❤️❤️
Good lecture. Thank you
Thank you very much 💖 very good work
THANK YOU for this video!!!
can you do a vedio about the cori cycle?
Thank you so much 🙏♥️♥️♥️
Pyruvate an NH3 can form alanine directly why is there glutamate in between?
thank you
realy thank you from heart
Perfect!
Awesome 👌🏽♥️
nobody did such a video in german thx
For the latter pathway you metioned that involves the glutamine synthetase enzyme, our professor is having us learn this pathway and I have a question about the different shuttles that transport molecules across the membrane between the matrix and the cytosol within the liver. As I understand it, there are at least two antiporters that are used in conjunction with the urea cycle, the Malate/𝞪-ketoglutarate antiporter and the Glutamate/Aspartate antiporter. I understand that Glutamine is being shuttled into the liver to release the two ammonium ions to be used in urea formation, however, what is the purpose of a glutamate/aspartate shuttle if it's glutamine that's being shuttled to the liver and not glutamate? Is glutamate also somehow transported to the liver to release ammonium for the urea cycle, or are these antiporters different form how I understand them?
The glutamate produced from the deamination of glutamine in the liver mitochondria needs to be transported back to the cytosol for further utilization. This is where the glutamate/aspartate antiporter is involved. It exchanges glutamate (generated from the deamination of glutamine) for aspartate, allowing the cytosolic glutamate to be used for various purposes.
The aspartate generated in the cytosol through this exchange can participate in the urea cycle as well. Aspartate is involved in the synthesis of argininosuccinate, an intermediate in the urea cycle.
So, to summarize, the glutamate/aspartate antiporter is not directly involved in shuttling glutamine to the liver for ammonia release. Its primary role is to transport glutamate (derived from the deamination of glutamine) back to the cytosol and exchange it for aspartate, which has various metabolic roles, including its involvement in the urea cycle.
Once in the liver, does the reansamination back to Glutamate and Pyruvate occur in the cytoplasm or the mitochondrial matrix of the cell? The deamination of Glutamate occurrs in the matrix (since it's toxic for the cell and because the Urea cycle's first phase is there) so if Glu is transaminated in the cytoplasm, does it diffues into the matrix afterwards?
Glutamate / pyruvate transamination takes place in the CYTOPLASM , a reaction catalyzed by the enzyme (ALT) , as pyruvate is the end product of glycolysis , which takes place in the cytoplasm !While Glutamate / oxaloacetate transamination takes place in the MITOCHONDRIA , a reaction catalyzed by the enzyme (AST) , as oxaloacetate is an intermediate of Kreb's cycle , which takes place in the mitochondrial matrix !
Amazing 🌹❤️❤️
I thought that NH4+ + alfa-ketoglutarate formed Glu. And Glu + pyr formed Ala.
Thanks sir
so glad you're back :)))
can you tell what will be the next subject after biochem if any?
I hope some advanced human physiology or something usefull for med students but whatever it is it will be great for sure!!
Thanks! I haven't decided yet but something that will definitely be helpful to medical students. Some sort of combination of physiology/pathophysiology.
sounds amazing!! can't ever thank you enough. It's good to see that real good people like you exist.
Thank you ..
It is useful so much
but .. could you please write the structures?
Thats not always possible, given the limited amount of space. But of course you can always look up the structures yourself ;)
Ok .. Thanx
Don't worry, when I can I always draw out the structures!
+AK LECTURES (Andrey K) Thanx .. when I had an immunity exam .. I watched all yours videos .. they are very helpful ..
Is this the same as Cori Cycle?
what is the process of Alanine become Glutamate??? thank you
glucose isnt formed from glycogen in muscles due to the absence of glucose 6 phospatase
thank u
How come only branched chain amino acids can be broken down in muscle tissue and what are the enzymes that do so?
Branched chain amino acids (Ile, Leu, Val) cannot be taken directly to the liver to be transaminated -- if this was the case, the glucose-alanine cycle would serve no purpose. To clarify, non-branched amino acids can be transaminated directly in the liver but branched ones cannot b/c the liver doesn't have the necessary enzymes (aminotransferases) in order to metabolize these molecules.
Legend
Glutamate transfer it's amino group to pyruvate to form alanine ! 🤔 not like shown in diagram I think !
A1 sir i am afghan student in Pakistan i lesson to you
this man is single-handedly getting me through med school
I FKN LOVE YOU !!!!!!!!!!
So ultimately