Metabolism of phenylalanine and tyrosine

Summary

This script delves into the metabolism of the aromatic amino acids phenylalanine and tyrosine by liver cells, highlighting their conversion into acetyl acetate and fumarate. These compounds serve as precursors for ketone bodies and glucose, respectively, demonstrating the dual role of these amino acids as both gluconeogenic and ketogenic. The detailed enzymatic processes, including the function of phenylalanine hydroxylase and tyrosine amino transferase, are outlined, culminating in the formation of essential fuel molecules for the body.

Takeaways

• 🌟 Phenylalanine and tyrosine are aromatic amino acids that can be metabolized by liver cells to form acetyl acetate and fumarate.
• 🔍 Acetyl acetate is used for ketone body formation, while fumarate is used for glucose production, making these amino acids both glucogenic and ketogenic.
• 🧬 The first step in the process involves converting phenylalanine to tyrosine, catalyzed by the enzyme phenylalanine hydroxylase.
• 🌀 Phenylalanine hydroxylase is a mixed function oxygenase, utilizing diatomic oxygen to form tyrosine and water.
• 💧 The enzyme requires tetrahydrobiopterin for its activity, which is synthesized from dihydrobiopterin with the help of NADPH and dihydrofolate reductase.
• ♻️ Dihydropyridine reductase regenerates tetrahydrobiopterin, allowing for its reuse in the reaction.
• 🔄 Tyrosine amino transferase, using PLP (pyridoxal phosphate), transfers the alpha amino group from tyrosine to an alpha keto acid, forming p-hydroxyphenylpyruvate.
• 🌀 p-Hydroxyphenylpyruvate dioxygenase removes a carbon dioxide molecule and adds both atoms of diatomic oxygen to the substrate, forming homogentisate.
• 🔄 Another dioxygenase, homogentisate 1,2-dioxygenase, further modifies the molecule to form allyl acetyl acetate.
• 🔄 An isomerase, using glutathione, converts allyl acetyl acetate into fumarate and acetyl acetate.
• 🌿 The final step cleaves the bond in acetyl acetate to form fumarate and acetyl acetate, which can be used for glucose and ketone body synthesis, respectively.

Q & A

What are the two aromatic amino acids discussed in the script?

The two aromatic amino acids discussed in the script are phenylalanine and tyrosine.

How are phenylalanine and tyrosine related to glucose and ketone bodies?

Phenylalanine and tyrosine are known as glucogenic and ketogenic amino acids because they can be metabolized to form both glucose and ketone bodies.

What is the first step in the metabolic pathway of phenylalanine and tyrosine?

The first step is the transformation of phenylalanine into tyrosine, catalyzed by the enzyme phenylalanine hydroxylase.

What type of enzyme is phenylalanine hydroxylase?

Phenylalanine hydroxylase is a mixed function oxygenase, which uses a diatomic oxygen molecule for the reaction.

What is the role of tetrahydrobiopterin in the first step of the metabolic pathway?

Tetrahydrobiopterin provides the reducing power necessary for phenylalanine hydroxylase to catalyze the conversion of phenylalanine to tyrosine.

How is tetrahydrobiopterin synthesized in our cells?

Tetrahydrobiopterin is synthesized from dihydrobiopterin in the presence of NADPH and an H+ ion, catalyzed by the enzyme dihydrofolate reductase.

What is the purpose of the enzyme dihydropyridine reductase in this metabolic pathway?

Dihydropyridine reductase is used to regenerate tetrahydrobiopterin from its reduced form, using the reducing power of NADPH.

What enzyme is responsible for transferring the alpha amino group from tyrosine to an alpha keto acid?

The enzyme responsible for this transfer is tyrosine aminotransferase, which uses pyridoxal phosphate (PLP) for the reaction.

What intermediate is formed after the removal of carbon dioxide from the substrate molecule in the metabolic pathway?

The intermediate formed is homogentisate, after the carbon dioxide is removed and two oxygen atoms are attached to the substrate.

What type of enzyme is used to isomerize homogentisate to form fumarate and acetyl acetate?

An isomerase enzyme, specifically homogentisate isomerize, is used to isomerize homogentisate to form fumarate and acetyl acetate.

What is the final product of the metabolic pathway for phenylalanine and tyrosine?

The final products of the metabolic pathway are acetyl acetate and fumarate, which can be used to form ketone bodies and glucose, respectively.

Outlines

00:00

🔬 Metabolism of Phenylalanine and Tyrosine

This paragraph explains how the liver cells metabolize aromatic amino acids phenylalanine and tyrosine into acetyl acetate and fumarate. Acetyl acetate is used to form ketone bodies, while fumarate is used to form glucose, making these amino acids both glucogenic and ketogenic. The first step involves transforming phenylalanine into tyrosine using the enzyme phenylalanine hydroxylase, a mixed-function oxygenase, which uses diatomic oxygen and the reducing power of tetrahydrobiopterin.

05:01

🧪 Detailed Biochemical Process of Tyrosine Formation

The paragraph continues with the detailed biochemical process of forming tyrosine from phenylalanine. It describes how phenylalanine hydroxylase, aided by tetrahydrobiopterin and NADPH, catalyzes the conversion. The regeneration of tetrahydrobiopterin involves the enzyme dihydropyridine reductase. The next steps include the use of tyrosine amino transferase, pyridoxal phosphate (PLP), and several dioxygenase enzymes to form intermediate compounds like hydroxyphenylpyruvate and homogentisate, eventually leading to the formation of acetyl acetate and fumarate. These intermediates can be used for energy production in the form of ketone bodies and glucose.

Keywords

💡Aromatic amino acids

Aromatic amino acids are a group of amino acids that have a ring structure attached to the side chain. In the context of the video, phenylalanine and tyrosine are highlighted as examples of aromatic amino acids. They are crucial for the metabolic processes discussed, as they can be metabolized to form acetyl acetate and fumarate, which are important for the production of glucose and ketone bodies.

💡Phenylalanine

Phenylalanine is an essential amino acid that cannot be synthesized by the human body and must be obtained through diet. It plays a central role in the script as it is the starting point for the metabolic pathway described. Phenylalanine is converted into tyrosine, which is then further metabolized to form various compounds.

💡Tyrosine

Tyrosine is another amino acid that is synthesized from phenylalanine, as outlined in the script. It is a non-essential amino acid in humans, meaning the body can produce it from phenylalanine. Tyrosine is a precursor for various important biochemicals, including neurotransmitters and hormones.

💡Acetyl acetate

Acetyl acetate is a compound formed during the metabolism of phenylalanine and tyrosine. It is mentioned in the script as a substance that can be used by parasites to form ketone bodies. This highlights the dual role of these amino acids in both glucose and ketone body production.

💡Fumarate

Fumarate is an intermediate in the citric acid cycle and is also formed during the metabolism of phenylalanine and tyrosine, as described in the script. It is significant because it can be used in the formation of glucose, demonstrating the versatility of these amino acids in metabolic pathways.

💡Phenylalanine hydroxylase

Phenylalanine hydroxylase is the enzyme that catalyzes the conversion of phenylalanine to tyrosine. It is a mixed function oxygenase, utilizing molecular oxygen to perform this reaction. The script emphasizes its role in the first step of the metabolic pathway under discussion.

💡Tetrahydrobiopterin

Tetrahydrobiopterin is an electron carrier molecule required for the function of phenylalanine hydroxylase. It is synthesized within the cells and is essential for the conversion of phenylalanine to tyrosine, as depicted in the script.

💡Dihydrofolate reductase

Dihydrofolate reductase is an enzyme involved in the regeneration of tetrahydrobiopterin. It uses NADPH to reduce dihydrobiopterin to tetrahydrobiopterin, as mentioned in the script, which is crucial for the continued function of phenylalanine hydroxylase.

💡Tyrosine amino transferase

Tyrosine amino transferase is the enzyme responsible for transferring the alpha amino group from tyrosine to an alpha-keto acid, forming p-hydroxyphenylpyruvate. This step is part of the metabolic pathway described in the script, leading to the formation of acetyl acetate and fumarate.

💡PLP (Pyridoxal phosphate)

PLP, or pyridoxal phosphate, is a derivative of vitamin B6 and acts as a coenzyme for many aminotransferases, including tyrosine amino transferase. It is essential for the transfer of amino groups in the metabolic reactions described in the script.

💡p-Hydroxyphenylpyruvate dioxygenase

p-Hydroxyphenylpyruvate dioxygenase is an enzyme that catalyzes a reaction in the metabolic pathway of phenylalanine and tyrosine. It uses molecular oxygen to convert p-hydroxyphenylpyruvate into homogentisate, as detailed in the script.

💡Isomerase

Isomerase is a type of enzyme that catalyzes the isomerization of a compound, changing its structure without altering its molecular formula. In the script, an isomerase is mentioned as part of the process that converts maleylacetoacetate into fumarate, illustrating the enzyme's role in the metabolic pathway.

💡Fumarate acetyl acetate

Fumarate acetyl acetate is an enzyme that catalyzes the final step in the metabolic pathway described, cleaving a bond in the compound to form acetyl acetate and fumarate. This step is crucial for the production of ketone bodies and glucose, as outlined in the script.

Highlights

The aromatic amino acids phenylalanine and tyrosine are discussed for their metabolic pathways in liver cells.

Phenylalanine and tyrosine are identified as glucogenic and ketogenic amino acids due to their ability to form glucose and ketone bodies.

The first step of the metabolic process involves the conversion of phenylalanine to tyrosine catalyzed by phenylalanine hydroxylase.

Phenylalanine hydroxylase is a mixed function oxygenase, utilizing diatomic oxygen for the conversion process.

The reducing power of tetrahydrobiopterin is essential for the catalytic activity of phenylalanine hydroxylase.

Tetrahydrobiopterin is synthesized by cells starting from dihydrobiopterin in the presence of NADPH and H+.

Dihydropyridine reductase is used to regenerate tetrahydrobiopterin for continuous use in the reaction.

Tyrosine amino transferase and PLP (pyridoxal phosphate) are involved in the transfer of the alpha amino group from tyrosine.

The formation of p-hydroxyphenylpyruvate occurs after the removal of the alpha amino group from tyrosine.

p-Hydroxyphenylpyruvate dioxygenase catalyzes the addition of both oxygen atoms from diatomic oxygen to the substrate molecule.

The intermediate compound homogentisate is formed after the removal of carbon dioxide.

A second dioxygenase, homogentisate 1,2-dioxygenase, is used to form the intermediate allyl-acetyl acetate.

An isomerase enzyme and glutathione activity are responsible for the isomerization of allyl-acetyl acetate to fumarate.

The final step involves the cleavage of a sigma bond by fumarate, resulting in the formation of acetyl acetate and fumarate.

Acetyl acetate can be used by parasites to form ketone bodies, while fumarate can be used to form glucose.

The metabolic pathways of phenylalanine and tyrosine are crucial for the production of fuel molecules in the body.

Transcripts

the next two amino acids that we're

going to focus on will be the aromatic

amino acids phenylalanine and tyrosine

and we're going to look at how our liver

cells can metabolize these two amino

acids ultimately forming acetyl acetate

and fumarate now acetyl acetate can be

used by our parasites to form ketone

bodies while fumarate can be used to

form glucose and that's exactly why

these two amino acids phenylalanine and

tyrosine are known as glucose anak and

ketogenic amino acids because we can use

them to ultimately form both glucose and

ketone bodies

let's begin by examining step one and

actually what step 1 shows us is we can

transform phenyl alanine directly into

tyrosine and this is precisely how our

cells can synthesize tyrosine by

beginning with phenyl alanine now the

enzyme that catalyzes step one is phenyl

alanine hydroxylase and this enzyme is

part of a category of enzymes we call

mixed function oxygen ASIS so this is a

mixed function oxygenase and what that

means is it uses a diatomic oxygen it

takes one of the oxygen atoms within

this diatomic molecule places it on this

reactant the phenyl alanine and this

basically forms the tyrosine and this

oxygen is shown here now the other

oxygen atom goes to form water

that's exactly why water is released

here so phenyl alanine hydroxylase is a

mixed function oxygenates now in order

for the phenyl alanine hydroxylase to be

able to catalyze this step it has to use

the reducing power of an electron

carrier molecule we call

tetrahydrobiopterin now

tetrahydrobiopterin is actually not a

vitamin because our cells can synthesize

this molecule and to synthesize this

molecule we basically begin with dye

hydro

by Opteron so in the presence of NADPH

and an H+ ion the enzyme dihydrofolate

reductase basically takes the dye Hydra

by op turan and transfers the reducing

power from NADPH on to this molecule to

give us tetrahydrobiopterin and then and

then this mixed function oxygenates this

enzyme phenylalanine hydroxylase uses

the reducing power of

tetrahydrobiopterin to basically form

tyrosine and of course we also use up

the reducing power of this molecule to

form Quinn a node dye hydra by operon

now to regenerate back the

tetrahydrobiopterin so that it can be

used again in this reaction we use an

enzyme called dihydropyridine reductase

and this enzyme takes the reducing power

of NADPH transfers it onto this molecule

to form back the tetrahydrobiopterin so

that again we can use the reducing power

of this molecule to undergo this first

step so again in the first step we

utilize a phenyl alanine a diatomic

water molecule we use NADPH to basically

give us this and by using the reducing

power of this molecule we transform the

phenyl alanine into tyrosine so one of

the oxygen atoms goes onto this ring of

the phenyl alanine and the other one is

used to form a water molecule now once

we form tyrosine what happens next well

next we basically have to use an amino

transferase to transfer the Alpha amino

group from tyrosine onto an alpha keto

acid and so we have the enzyme tyrosine

amino transferase and just like any mu

transferase this one has to use PLP so

pyridoxal phosphate we transfer this

alpha amino group from the tyrosine onto

an alpha key to glue direct now the

alpha ketoglutarate upon

seeing that amino group eform glutamate

upon removing the alpha immune agree

from tyrosine we form this alpha keto

acid the P hydroxy phenyl pyruvate now

once we form this molecule the next step

is to use a dioxygen ace and unlike an

oxygen ace where one of the oxygen atoms

was used to form water and the other

oxygen atom went on to the phenyl

alanine to form the tyrosine an enzyme

that we call dioxygen ace uses a

diatomic water a diatomic oxygen and it

uses both atoms of that diatomic oxygen

to attach it onto that substrate

molecule so in this step we basically

want to remove this carbon dioxide and

we want to use both of the oxygen atoms

and attach them onto this substrate to

basically form an intermediate we call

how magenta say so the enzyme that

catalyzes this step is P hydroxy phenyl

pyruvate dioxygenase and so ultimately

we attach an oxygen here onto this

carbon and the other oxygen goes onto

this ring here so now we have two oxygen

atoms here two oxygen atoms here and

this carbon dioxide group was basically

removed as carbon dioxide now in the

next step we want to use yet again a

dioxygen ace so now we use homogeneous

eight one two dioxygen ace again we use

a diatomic water a diatomic oxygen one

of the oxygen is basically attached onto

this carbon the other oxygen is attached

onto this carbon so ultimately we break

this Sigma bond and PI bond within this

ring we attach the oxygen here and here

to form this intermediate form allyl

acetyl acetate now in the next step we

basically want isomerize so we want to

transform this assist group into

a trans group so we have the Syst double

bond here but we want to form a trans

double bond as shown here so the enzyme

that catalyzes this step is an isomerase

so we have malleolus edo acetate

isomerize which uses the activity of

glutathione to basically form this

molecule the four fumarole

acetyl acetate and the final step in

this reaction in which we ultimately

want to cleave this Sigma bond here by

using essentially a water molecule this

is this is catalyzed by fumarole acetyl

acetate and so ultimately we form a

fumarate because once we cleave this

bond the oxygen essentially attaches

onto this carbon and this becomes a ch3

and so we form acetyl acetate and

fumarate and now this can be used to

form a ketone body and this can be used

to form our glucose so we see that

inside ourselves we can transform phenyl

alanine into tyrosine and so ultimately

we can basically form tyrosine within

this step and both phenyl alanine and

tyrosine by following these series of

steps can be transformed into these

carbon skeletons acetyl acetate and

fumarate and these can ultimately be

used to form fuel molecules so either

ketone bodies in this case or glucose

molecules in this case