20241025_Aa_metabolism

Amino acids are crucial as they make up proteins with specific functions and serve as energy reserves when dietary carbohydrates are low. They act as precursors for glucose through gluconeogenesis.

Nitrogen balance indicates the relationship between protein anabolism and catabolism. It remains relatively constant despite dynamic changes in protein synthesis and degradation, particularly in the liver, which is the primary site for amino acid metabolism.

The major fate of carbon in most amino acids is its conversion to glucose through gluconeogenesis, which is essential for energy production, especially when carbohydrate intake is low.

The breakdown of amino acids primarily occurs in the liver, where half of their nitrogen is converted to NH4+ and the other half to aspartate, resulting in the production of urea and glucose.

The synthesis of urea and glucose is linked in amino acid metabolism as they share a common intermediate, highlighting the interconnectedness of nitrogen and carbon metabolism in the liver.

Cysteine degradation to pyruvate may proceed by at least three different pathways.

Phenylalanine and tyrosine are considered both ketogenic and glucogenic because:

• Part of their carbon skeletons yield acetoacetate (ketogenic).
• The other part yields fumarate (glucogenic).

In patients with phenylketonuria (PKU), the lack of the enzyme phenyltyrosine 4-monooxygenase leads to:

• Accumulation of phenylpyruvic acid in the blood.
• Excretion of phenylpyruvic acid in urine.
• Impaired normal brain development during childhood, resulting in severe mental retardation. Restricting dietary phenylalanine during childhood can prevent this impairment.

Leucine is converted to acetyl CoA through the following steps:

1. Leucine (CH3CHCH2CHCOOH with NH2) is converted to α-Ketoisocaproic acid.
2. This is then converted to Isovaleryl-CoA.
3. Next, it transforms into β-Methylcrotonyl-CoA.
4. Then, it becomes β-Methylglutaconyl-CoA.
5. Finally, it degrades into Acetyl-CoA and Acetoacetic acid via β-Hydroxy-β-methyl-glutaryl-CoA.

Each step is facilitated by specific enzymes that are involved in the reactions.

Excess amino acids are either excreted through renal excretion (approximately 0.9 to 1.0 gm/day) or converted into various nonprotein nitrogenous tissue constituents.

Transamination and deamination are processes that lead to the conversion of amino acids in the liver, resulting in:

1. Formation of α-keto acids for energy production.
2. Production of ammonia, which is then converted to urea for excretion.

Dietary proteins are broken down into amino acids, which then influence muscle proteins through the action of insulin. Additionally, these amino acids are transported to the liver, where they contribute to glucose production and urea synthesis.

Insulin facilitates the uptake of amino acids into muscle cells, promoting the synthesis of muscle proteins and enhancing muscle growth and repair.

Glucose produced in the liver is utilized by beta cells to regulate insulin secretion, which in turn affects brain function by providing energy and influencing metabolic processes.

Dietary proteins are converted to amino acids, which influence insulin secretion. Insulin then affects brain function by regulating glucose availability and metabolic signaling pathways.

Amino acids converge into terminal pathways leading to pyruvate, acetylCoA, or intermediates of the TCA cycle.

Amino acid metabolism primarily takes place in the liver of vertebrates, with significant activity also in the kidney.

The two major pathways involved in the removal of the α-amino group are transamination and oxidative deamination.

The α-amino nitrogen atoms are ultimately excreted in the urine as urea, ammonia, or uric acid, depending on the species.

Many intermediates of amino acid catabolism have important functions in the cell, such as acting as neurotransmitters and precursors of porphyrin biosynthesis.

Transamination is a major reaction involving all amino acids except lysine and threonine. It involves the transfer of an amino group from a donor a-amino acid to a recipient a-keto acid, resulting in the conversion of the keto acid into an amino acid and the donor amino acid into a keto acid.

Transaminases play two major roles in amino acid metabolism:

1. Interconversion of amino acids to increase the amount of one that may be in short supply, allowing for both synthesis and degradation of amino acids.
2. Channeling of amino groups ultimately to glutamate and aspartate, which can be converted to urea if in excess.

The common prosthetic group shared by transaminases is pyridoxal phosphate.

Aspartate aminotransferase (AAT) and alanine aminotransferase (ALT) are clinically important enzymes used in the diagnosis of diseases, as they catalyze key transamination reactions involving amino acids.

Transaminase catalyzes the reaction where glutamate reacts with pyruvate to produce alpha-ketoglutarate and alanine. This enzyme facilitates the transfer of an amino group from glutamate to pyruvate, forming alanine and regenerating alpha-ketoglutarate.

Pyridoxine contains the following key functional groups:

• Hydroxyl (OH) group
• Methyl group
• Two hydroxymethyl groups (-CH2OH)

Pyridoxal differs from Pyridoxine by the presence of an aldehyde group (CHO) in addition to the hydroxyl (OH) group, methyl group, and hydroxymethyl group (-CH2OH).

The phosphate group in Pyridoxal phosphate is negatively charged and plays a crucial role in the activation of the molecule, making it a coenzyme in various enzymatic reactions involving amino acids.

Pyridoxamine consists of a six-membered aromatic ring with a nitrogen atom, containing:

• Hydroxyl (OH) group
• Methyl group
• Aminomethyl group (-CH2NH2)

Pyridoxamine phosphate includes a phosphate group (-CH2-O-P-O-) in addition to the components of Pyridoxamine, which enhances its role as a coenzyme in biochemical reactions.

The Schiff's base consists of pyridoxal phosphate linked to an amino acid, which has the structure R1-CH(R2)-COOH, where R1 is the variable side chain and R2 is the amino group that forms the linkage with the aldehyde group of pyridoxal phosphate.

The initial reactant is an alpha-amino acid, which has a structure consisting of a carbon atom bonded to a hydrogen, an R1 group, an NH2 group, and a COOH group.

Pyridoxal phosphate-enzyme acts as a coenzyme that facilitates the reaction between the alpha-amino acid and water, leading to the formation of an aldimine and subsequently a ketimine.

The products formed are pyridoxamine phosphate-enzyme and an alpha-keto acid.

The starting reactant is an alpha-keto acid, which consists of a carbon atom double bonded to an oxygen atom and single bonded to an R2 group and a COOH group.

Pyridoxamine phosphate-enzyme reacts with the alpha-keto acid and water to form a ketimine, which can further react to form an aldimine.

The final products are pyridoxal phosphate-enzyme and an alpha-amino acid.

Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of L-glutamate, converting it into α-ketoglutarate while releasing NH₄⁺ ions. It is an allosteric enzyme that is inhibited by ATP, GTP, and NADH, and stimulated by ADP, GDP, and certain amino acids. GDH is crucial as it is the only active dehydrogenase for glutamate in most organisms.

The activity of GDH is regulated by various factors: it is inhibited by ATP, GTP, and NADH, while it is stimulated by ADP, GDP, and certain amino acids. Additionally, its activity can be influenced by thyroxine and certain steroid hormones.

The net reaction of the deamination process involving alanine and glutamate is:

Alanine + NAD⁺ + H₂O → pyruvate + NADH + NH₄⁺.

This shows the conversion of alanine and α-ketoglutarate to pyruvate and glutamate, followed by the conversion of glutamate to α-ketoglutarate, NADH, and NH₄⁺.

The substrates for the reaction catalyzed by glutamate dehydrogenase are glutamate, NAD⁺, and H₂O. The products of this reaction are α-ketoglutarate, NADH, and NH₄⁺.

L-amino acid oxidase is a flavin-linked enzyme that plays a relatively minor role in amino acid deamination. It contains tightly bound FMN as the prosthetic group and is present in the endoplasmic reticulum of the liver and kidneys, where it likely functions in the deamination of lysine. It is also found in large amounts in snake venom.

D-amino acid oxidase functions to initiate the degradation of D-amino acids that arise from the enzymatic breakdown of the cell wall peptidoglycans of intestinal bacteria. It contains FAD as its prosthetic group.

The amino groups of serine, homoserine, threonine, cysteine, and homocystine can be removed non-oxidatively by a group of dehydratases. Pyridoxal phosphate serves as the coenzyme in this process.

The products formed from the non-oxidative deamination of amino acids are ammonia (NH3) and the corresponding keto acid.

Amino acids serve as precursors for various metabolites in the Citric Acid Cycle, contributing to energy production and metabolic pathways. They can be converted into key intermediates such as Pyruvate, Acetyl CoA, and Oxaloacetate, facilitating the cycle's function in cellular respiration.

The three principal routes for the metabolic disposal of ammonia are: 1. Conversion to carbamoyl phosphate leading to urea; 2. Formation of aspartate which can lead to asparagine; 3. Conversion to α-ketoglutarate which leads to glutamate. A minor route involves the formation of asparagine.

Impaired urea formation can lead to ammonia intoxication, especially in patients with hepatomegaly and impaired liver function.

Ammonia is extremely toxic at high concentrations, necessitating its immediate conversion to nontoxic metabolites for reuse or excretion, depending on the body's needs.

The formation of glutamate involves the reversal of the glutamate dehydrogenase reaction, where α-ketoglutarate combines with ammonia (NH3) and NAD(P)H to produce glutamate, water, and NAD(P)+.

Transamination allows the amino group from glutamate to be available for the formation of other amino acids as needed.

Glutamate synthase catalyzes the reaction where α-ketoglutarate, glutamine, NADPH, and H+ produce two molecules of glutamate and NADP+.

The bacterial enzyme glutamate synthase requires FAD, FMN, and iron-sulphur centers for its activity.

Glutamine is formed from glutamate by the addition of ammonia (NH3) and ATP, resulting in the production of glutamine, ADP, and inorganic phosphate (P).

Glutamine synthetase catalyzes the formation of glutamine, which serves as a temporary nontoxic storage and transport form of nitrogen. It is crucial for detoxifying ammonia formed from amino acid catabolism, particularly in the brain.

Glutamine's amide-N can be utilized in the biosynthesis of several amino acids (such as glutamate, histidine, and tryptophan), purine and pyrimidine nucleotides, and amino sugars, highlighting its central role in nitrogen metabolism.

The urea cycle is the third major route for the metabolic disposal of ammonia, occurring exclusively in the liver of mammals. It converts toxic ammonia into urea, which can be safely excreted.

The formation of glutamate and glutamine can deplete alpha-ketoglutarate (a-kg), which may interfere with the TCA cycle and energy generation, contributing to the toxicity of ammonia in animals.

Asparagine synthetase catalyzes the conversion of aspartate to asparagine using ammonia or glutamine as substrates. The reaction also involves ATP, producing asparagine, AMP, inorganic phosphate (Pi), and glutamate (Glu).

The products of the reaction are asparagine, AMP, inorganic phosphate (Pi), and glutamate (Glu).

The reaction catalyzed by asparagine synthetase accounts for much less ammonia assimilation compared to other pathways, indicating its limited role in ammonia incorporation.

Ornithine acts as a carrier for the incoming amino group and is involved in the conversion of carbamoyl phosphate to citrulline in the mitochondria. It is also transported across the mitochondrial membrane to facilitate the cycle.

The urea cycle utilizes 2 ATP molecules to convert ammonia and carbon dioxide into carbamoyl phosphate, which is a key step in the cycle. Additionally, ATP is involved in the conversion of argininosuccinate to arginine, producing AMP and PPᵢ.

Fumarate is produced during the conversion of argininosuccinate to arginine. It plays a role in the TCA cycle (Krebs cycle) as it can be further metabolized, linking the urea cycle to energy metabolism.

Argininosuccinate is an intermediate in the urea cycle that is formed from citrulline and aspartate. It is subsequently converted to arginine and fumarate, facilitating the removal of excess nitrogen from the body.

Carbamoyl phosphate synthetase catalyzes the formation of carbamoyl phosphate from free ammonia and carbon dioxide, using two molecules of ATP. It is specialized for urea synthesis and requires N-acetylglutamate as a stimulatory allosteric activator.

The mitochondrial carbamoyl phosphate synthetase uses free ammonia as the nitrogen donor, while the cytosolic form uses glutamine as the nitrogen donor. The cytosolic enzyme is inhibited by UTP and is involved in pyrimidine nucleotide biosynthesis.

The substrates are HCO3-, NH4+, and 2 ATP, and the products are carbamoyl phosphate, 2 ADP, and acetylglutamate.

N-acetylglutamate acts as a stimulatory allosteric activator for carbamoyl phosphate synthetase, enhancing the enzyme's activity in the formation of carbamoyl phosphate.

Ornithine transcarbamoylase catalyzes the reaction where carbamoyl phosphate condenses with ornithine to form citrulline in the mitochondrial matrix.

Citrulline exits the mitochondria via a specific transporter known as citrulline ornithine translocase, which allows it to pass into the cytosol for further reactions in the urea cycle.

The second amino group required for urea synthesis comes from aspartate, which acquires it from glutamate through the action of aspartate aminotransferase in the cytosol.

The enzyme that catalyzes the reaction between citrulline and aspartate to form argininosuccinate is argininosuccinate synthetase, which requires magnesium for its activity.

The reactants are citrulline and aspartate, and the products are argininosuccinate, AMP, and PPi (pyrophosphate).

Pyrophosphate is hydrolyzed by pyrophosphatase to inorganic phosphate, which pulls the overall reaction towards the right, favoring the formation of argininosuccinate.

The products of the reaction catalyzed by argininosuccinase are arginine and fumarate.

The arginine formed from argininosuccinate becomes the immediate precursor of urea, which is a key component of the urea cycle.

Fumarate is hydrated to malate and then oxidized to oxaloacetate (OAA) in the TCA cycle, which can be converted to aspartate by transamination, allowing the cycle to repeat.

The enzyme that mediates the hydrolysis of arginine to urea and ornithine is arginase.

Arginase is primarily found in the liver of mammals.

The ornithine formed can pass back into the mitochondria, allowing the urea cycle to be repeated.

Ornithine is significant in the urea cycle because it is regenerated, meaning only catalytic amounts are required for the cycle to continue.

The overall equation of the urea cycle is:

2NH3 + CO2 + 3ATP + 3H2O → urea + 2ADP + AMP + 4Pi

N-acetylglutamate acts as a positive effector of carbamoyl phosphate synthetase, which is crucial for regulating urea formation at the committed step in the pathway.

The amount of urea excreted in the urine of a normal adult averages 25-30g/day and is increased or decreased in direct proportion to the amount of proteins ingested.

Measurements of blood urea nitrogen (BUN) levels provide a sensitive clinical test of kidney function.

The excretion of ammonia is much less, about 2.5-4.5% of total urinary nitrogen, but it is important in maintaining acid-base balance in the body.

Glutamine synthetase converts glutamate to glutamine using ATP and water, while also incorporating a nitrogen atom (NH₄) and releasing ADP and inorganic phosphate (Pi).

In the liver, glutamine is converted back to glutamate by glutaminase, releasing water. Glutamate can then enter the urea cycle, converting to urea and releasing a nitrogen atom (NH₄), which is crucial for detoxifying ammonia in the body.

In muscle tissue, glutamate dehydrogenase converts amino acids to glutamate, releasing a nitrogen atom (NH₄). This process is part of a cycle that also involves conversion to pyruvate and is similar to the processes in the liver.

The glucose-alanine cycle involves the conversion of pyruvate to alanine in both the liver and muscle. Alanine can then be converted back to pyruvate, which is further converted to glucose. This cycle is significant for transporting nitrogen and maintaining glucose levels in the body.

The amino acids that can be catabolized to pyruvate include alanine, glycine, serine, and cysteine.

The major alternative route for glycine degradation is:

Glycine + FH4 + NAD ⇆ Methylene-FH4 + CO2 + NH3 + NADH + H+

This reaction is reversible and is catalyzed by glycine synthase.

β-Hydroxy-β-methyl-glutaryl-CoA is an important precursor in the biosynthesis of cholesterol. It plays a crucial role in the metabolic pathway leading to the production of cholesterol from leucine degradation.

Threonine is metabolized through a less important pathway where:

1. Threonine is converted to α-ketobutyric acid by the enzyme threonine dehydratase.
2. This compound then undergoes oxidative decarboxylation to form propionyl CoA.
3. Propionyl CoA serves as a precursor for succinyl CoA.

Ornithine acts as an intermediate in the conversion of arginine to glutamate. The degradation pathway involves the conversion of arginine to ornithine, which then leads to the production of glutamate.

Glutamic acid can be acetylated to form N-acetylglutamate, which is an allosteric activator of the first step of the urea cycle reactions, enhancing the cycle's efficiency.

The final product of the a-ketoglutarate pathway is alpha-ketoglutarate, which is produced from glutamic acid.

N-acetylglutamate is significant because it acts as an allosteric activator for the first step of the urea cycle, thereby playing a crucial role in nitrogen metabolism.

The three amino acids that feed into the succinate pathway are Valine, Methionine, and Isoleucine.

Methylmalonyl CoA mutase is a coenzyme B12-dependent enzyme that converts L-methylmalonyl CoA in the succinate pathway.

Patients suffering from pernicious anemia are deficient in vitamin B12, leading to the excretion of large amounts of methylmalonic acid and propionic acid in their urine due to impaired conversion in the succinate pathway.

The carboxylation of propionyl-CoA yields D-methylmalonyl CoA, which is then converted to the L form by a racemase.

Phenylalanine 4-monooxygenase catalyzes the conversion of phenylalanine to tyrosine using O2 and NADPH, producing H2O and NADP+ as byproducts.

When tyrosine reacts with alpha-Ketoglutarate, it produces 4-Hydroxyphenylpyruvic acid and glutamate through the action of the enzyme tyrosine transaminase.

The enzyme 4-hydroxy-phenylpyruvic acid dioxygenase converts 4-Hydroxyphenylpyruvic acid into homogentisic acid while releasing CO2.

The reaction involving homogentisic acid catalyzed by homogentisic acid 1,2-dioxygenase produces 4-Maleylacetoacetic acid and is crucial for the further breakdown of aromatic amino acids.

4-Maleylacetoacetic acid is converted to 4-Fumaryl-acetoacetic acid by the enzyme maleylacetoacetic acid isomerase, which is then hydrolyzed by fumarylacetoscotase to yield fumaric acid and acetoacetic acid.

In the fumarate pathway, four carbon atoms from phenylalanine and tyrosine enter the TCA cycle via acetoacetyl-CoA and acetyl-CoA, while four remaining carbon atoms are converted to fumarate.

Asparagine is hydrolyzed to aspartic acid and ammonia: Asparagine + H2O → aspartic acid + NH3

Asparaginase is used as a chemotherapeutic drug in the treatment of some leukemic patients.

Aspartate undergoes transamination to form oxaloacetate (OAA) and glutamate.

Aspartate undergoes direct elimination of ammonia to yield fumarate: Aspartate → fumarate + NH3

Histidine is decarboxylated to yield histamine and CO2.

Agmatine is a precursor of spermine and spermidine, which are growth factors for some microorganisms and help stabilize membrane structures and ribosomes in many organisms.

Serotonin is a neurotransmitter that plays multiple regulatory roles in the nervous system, including mood regulation, sleep, and appetite control.

Serotonin is produced in the pineal gland and is synthesized from the amino acid tryptophan.

Serotonin serves as a precursor to melatonin, which is important for regulating light-dark cycles in animals and has antioxidant effects.

Serotonin is secreted by cells in the small intestine and regulates intestinal peristalsis, aiding in digestion.

Serotonin acts as a potent vasodilator, helping to regulate blood pressure.

Ornithine is the starting substrate that is converted to putrescine by the enzyme ornithine decarboxylase, releasing CO2 in the process.

The reaction of putrescine with decarboxylated S-adenosylmethionine, catalyzed by Propylaminotransferase I, produces spermidine and Methylthioadenosine.

Spermine is synthesized from spermidine through a reaction with decarboxylated S-adenosylmethionine, catalyzed by Propylaminotransferase II, resulting in the formation of Methylthioadenosine as a byproduct.

Decarboxylated S-adenosylmethionine acts as a key substrate in the reactions catalyzed by Propylaminotransferases I and II, facilitating the conversion of putrescine to spermidine and spermidine to spermine, respectively.

The initial substrate is Tyrosine.

Tyrosine hydroxylase catalyzes the conversion of Tyrosine to Dopa using O2, NADPH, and H4-biopterin.

Patients with Parkinson's disease have low levels of dopamine in certain brain regions, and since dopamine cannot cross the blood-brain barrier, they are often treated with Dopa to increase dopamine levels.

Dopamine metabolism in neurons is linked to schizophrenia, and drugs like chlorpromazine, which are dopamine antagonists, block dopamine binding to its receptors, helping to treat the condition.

The final product of the catecholamine biosynthesis pathway is Epinephrine.

The two main branches after dopaquinone are:

1. Leucodopachrome and further derivatives, leading to polymeric red melanins.
2. A reaction with cysteine, leading to polymeric black melanins.

LSD mimics serotonin at receptors in the central nervous system, leading to its psychoactive effects.

Fluoxetine (Prozac) blocks the uptake of serotonin into presynaptic receptors, which helps alleviate symptoms of depression and other psychiatric disorders.

The defective enzyme in Albinism is Tyrosine 3-monooxygenase, which is involved in the metabolism of the amino acid tyrosine. This enzyme catalyzes the conversion of tyrosine to DOPA, a precursor for melanin production.

The genetic disorder associated with a defect in homogentisic acid 1,2-dioxygenase is Alkaptonuria. This enzyme is crucial for the breakdown of homogentisic acid, leading to its accumulation in the body.

In Argininosuccinic acidemia, the defective enzyme is Argininosuccinate lyase, which plays a role in the urea cycle by converting argininosuccinate into arginine and fumarate, thus facilitating the removal of ammonia from the body.

In Cystinosis, the defect lies in the storage and/or release of cystine from lysosomes. This leads to the accumulation of cystine within lysosomes, causing cellular damage and various clinical symptoms.

The primary issue in Cystinuria is the defective renal and intestinal transport of cystine and certain other amino acids. This results in the excessive excretion of cystine in urine and can lead to kidney stones.

Hartnup's disease is characterized by a defect in the renal transport of neutral amino acids, leading to their impaired absorption and subsequent deficiency in the body.

In Histidinemia, the deficient enzyme is Histidine ammonia-lyase, which is responsible for the conversion of histidine to histamine and other metabolites, affecting histidine metabolism.

The defective enzyme in Homocystinuria is Cystathionine ẞ-synthase, which is crucial for the metabolism of homocysteine. Its deficiency leads to elevated levels of homocysteine, which is associated with cardiovascular diseases.

In Isovaleric acidemia, the impaired process is isovaleryl-CoA dehydrogenation, which is essential for the breakdown of the branched-chain amino acid leucine. This leads to the accumulation of isovaleric acid in the body.

In Maple syrup urine disease, there is a deficiency in branched-chain a-keto acid dehydrogenases, which are necessary for the metabolism of branched-chain amino acids (leucine, isoleucine, and valine). This leads to toxic accumulation of these amino acids, causing severe neurological damage if untreated.

The enzyme involved in the metabolism of phenylalanine is Phenylalanine 4-monooxygenase. Its deficiency leads to Phenylketonuria, a disorder characterized by the inability to metabolize phenylalanine, resulting in its toxic accumulation.

Valine transaminase is involved in the transamination process of valine, an essential amino acid. In Hypervalinemia, there is an excess of valine due to impaired metabolism, which can lead to various metabolic disturbances.

Vertebrates cannot synthesize all common amino acids and must obtain essential amino acids from their diet. In contrast, higher plants can synthesize all amino acids required for protein synthesis and can utilize ammonia, nitrite, or nitrate as nitrogen sources.

Leguminous plants can utilize atmospheric nitrogen due to the presence of symbiotic nitrogen-fixing bacteria in their root nodules, allowing them to synthesize amino acids from nitrogen in the air.

The biosynthetic pathways for amino acids are often complex, with 20 different multienzyme sequences for the 20 amino acids. These pathways are highly regulated, with controlling enzymes modulated by inhibitors and stimulators.

Nonessential amino acids have relatively short biosynthetic pathways, usually with fewer than five steps, while essential amino acids have more complex and longer pathways, often involving 5-15 steps.

The biosynthetic pathways for essential amino acids are generally similar in most species of bacteria and higher plants, although there may be species differences in certain individual steps.

Shikimic acid is a key intermediate in the biosynthetic pathway of aromatic amino acids, leading to the synthesis of important aromatic substances such as lignin, ubiquinone, and plastoquinone.

Glyphosate specifically inhibits the enzyme 5-enoylpyruvylshikimate-3-phosphate synthase in the shikimic acid pathway, which inhibits the growth of most crops and weed plants, making it an effective broad-spectrum herbicide.

Experiments on mutants of E. coli and Aerobacter aerogenes that require phenylalanine, tyrosine, and tryptophan for growth helped deduce the pathway of the biosynthesis of aromatic amino acids.

The synthesis of aromatic amino acids starts with C3 and C4 organic phosphates, which lead to Shikimate.

Chorismate is a key intermediate that leads to several compounds, including CoQ, p-Aminobenzoic acid, Prephenate, and Anthranilate.

From Prephenate, the aromatic amino acids Phenylalanine and Tyrosine are derived.

Anthranilate, along with PRPP, Gln, and Ser, leads to the synthesis of Histidine and Tryptophan.

Phenylalanine leads to the production of Coniferyl alcohol, which is a precursor for Lignin and Flavor components.

Tryptophan leads to the synthesis of Auxin, a plant hormone.

The shikimate pathway is crucial for the biosynthesis of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) and other important metabolites. It is a target for herbicides and is not present in animals, making it a key pathway for plant and microbial growth.

The conversion involves several enzymes:

1. 3-Deoxy-D-arabino-heptulosonic acid 7-phosphate synthase
2. 3-Dehydroquinate synthase
3. 3-Dehydroquinate dehydratase
4. Shikimate dehydrogenase
5. Chorismate synthase

These enzymes catalyze the steps leading to the formation of chorismate from the initial substrates.

The main products of the shikimate pathway include:

• Chorismate
• Shikimic acid
• Aromatic amino acids (phenylalanine, tyrosine, tryptophan)
• Other secondary metabolites such as flavonoids and alkaloids.

Allosteric (feedback) inhibition regulates the first reaction in the biosynthetic sequence by its end product, allowing for fine control over the rate of biosynthesis. This mechanism enables second-by-second adjustments and can involve complex interactions when multiple end products are present, leading to either concerted or cumulative inhibition of the first enzyme in the sequence.

Repression lowers the concentration of one or more enzymes in the biosynthetic pathway by acting at the DNA or RNA level. This mechanism is slower to respond to metabolic changes but maximizes the economy of amino acids and energy by preventing the synthesis of unused enzymes, leading to significant savings in amino acids.

Isozymes are different forms of enzymes that may be inhibited or repressed by different end products of the biosynthetic pathway. This allows for more nuanced regulation of amino acid biosynthesis, as seen with aldolase in the biosynthesis of aromatic amino acids, contributing to the overall complexity of regulation in different species.

The main regulatory mechanisms of amino acid biosynthesis in bacteria include:

1. Allosteric (feedback) inhibition - Fine control through feedback from end products.
2. Repression - Lowering enzyme concentrations at the DNA or RNA level for economic use of resources.
3. Control by isozymes - Different isozymes regulated by different end products, allowing for specific control.

These mechanisms are often complex and can vary between species.

The end products of the metabolic pathway are Tryptophan, Tyrosine, and Phenylalanine.

Aldolase isozymes facilitate the conversion of D-Erythrose 4-phosphate and Phosphoenolpyruvate through a series of intermediate compounds in the metabolic pathway.

Feedback inhibition in the metabolic pathway regulates the flow of metabolites, ensuring that the production of end products like Tryptophan, Tyrosine, and Phenylalanine is balanced according to the cellular needs.

ATP provides the energy required for the reaction, while NH3 acts as a nitrogen donor, facilitating the conversion of glutamic acid to glutamine through the process of amination.

The downstream products derived from glutamine include Tryptophan, Histidine, CTP, Carbamoyl phosphate, Glucosamine 6-phosphate, and AMP.

Glutamic acid serves as a precursor in the metabolic pathways that lead to the synthesis of glycine and alanine, indicating its role in amino acid metabolism.