BC 3- Amino acid metabolism

What is required for amino acid synthesis?

Carbon backbones and reduced nitrogen.

Where do carbon backbones for amino acids come from?

Intermediates of glycolysis, the citric acid cycle, and the pentose phosphate pathway.

What provides reduced nitrogen (NH₄⁺) for amino acid synthesis?

Glutamate and glutamine.

Where does amino acid biosynthesis occur in the cell?

cytosol

What form are biosynthetic amino acids in?

The L-form.

L-amino acid visual

What is transamination?

A reaction that transfers an amino group from an amino acid to a keto acid.

What type of molecules participate in transamination?

An α-amino acid and an α-keto acid.

What enzyme catalyzes transamination reactions?

Transaminases (aminotransferases).

What coenzyme is required for transamination?

Pyridoxal phosphate (PLP).

What vitamin is PLP derived from?

Vitamin B6.

What is glutamate’s main role in amino acid metabolism?

It is a major donor of amino groups for the synthesis of most other amino acids.

What is produced when glutamate donates an amino group in transamination?

α-ketoglutarate.

What is glutamine used for in nitrogen metabolism?

It provides amide nitrogen for biosynthesis of nitrogen-containing compounds.

What biomolecules can receive amide nitrogen from glutamine?

Asparagine, carbamoyl phosphate, and nucleotides.

What are the main routes for incorporating inorganic nitrogen into organic molecules?

Synthesis of glutamate and glutamine.

What roles do glutamate and glutamine play in metabolism?

They serve as major nitrogen donors in many metabolic reactions.

How is glutamate synthesized?

From α-ketoglutarate + NH₄⁺ + NADPH → glutamate + NADP⁺ + H₂O.

What is the key precursor for glutamate synthesis?

α-ketoglutarate.

How is glutamine synthesized?

Glutamate + NH₄⁺ + ATP → glutamine + ADP + Pi + H⁺.

What energy molecule is required to form glutamine?

ATP

What is glutamate dehydrogenase?

An enzyme that catalyzes the reversible conversion between glutamate and α-ketoglutarate.

What reaction does glutamate dehydrogenase catalyze (direction toward glutamate)?

α-ketoglutarate + NH₄⁺ + NAD(P)H → glutamate + NAD(P)⁺ + H₂O.

What reaction does glutamate dehydrogenase catalyze (breakdown direction)?

Glutamate → α-ketoglutarate + NH₄⁺ + NAD(P)H (or NAD(P)⁺ depending on direction).

What is the role of glutamate dehydrogenase in nitrogen metabolism?

It helps incorporate or release inorganic nitrogen (NH₄⁺) in amino acid metabolism.

Where does glutamate dehydrogenase act in metabolism?

It links amino acid metabolism with the citric acid cycle via α-ketoglutarate.

What is glutamine synthetase?

An enzyme that catalyzes the formation of glutamine from glutamate and ammonia.

What reaction does glutamine synthetase catalyze?

Glutamate + NH₄⁺ + ATP → glutamine + ADP + Pi + H⁺.

What is the main function of glutamine synthetase?

To incorporate inorganic nitrogen (NH₄⁺) into organic form (glutamine).

Why is glutamine synthetase important in metabolism?

It helps detoxify ammonia and provides nitrogen for biosynthesis.

What is required for glutamine synthetase activity?

ATP.

How is alanine synthesized?

By transamination of pyruvate.

What is the amino group donor in alanine synthesis?

Glutamate.

What is produced when glutamate donates an amino group in alanine synthesis?

α-ketoglutarate.

What is the key reaction in alanine synthesis?

Pyruvate + glutamate ⇌ alanine + α-ketoglutarate.

What is glutamate aminotransferase?

An enzyme that catalyzes transamination reactions involving glutamate, transferring its amino group to an α-keto acid to form a new amino acid and α-ketoglutarate.

What is the main reaction for alanine synthesis?

Alanine is formed by transamination of pyruvate using glutamate as the amino donor.

What enzyme catalyzes alanine synthesis?

Alanine aminotransferase (ALT)

What are the reactants in alanine synthesis?

Pyruvate + Glutamate

What are the products of alanine synthesis?

Alanine + α-ketoglutarate

Why is alanine synthesis important in metabolism?

It links amino acid metabolism with glycolysis (via pyruvate)

What is glutamate aminotransferase?

An enzyme that transfers amino groups between amino acids and α-keto acids (transamination).

How is aspartate synthesized?

By transamination of oxaloacetate using glutamate as the amino donor

What enzyme synthesizes aspartate?

Aspartate aminotransferase (AST)

What are the reactants for aspartate synthesis?

Oxaloacetate + Glutamate

What are the products of aspartate synthesis?

Aspartate + α-ketoglutarate

What cofactor is required for aspartate synthesis?

Pyridoxal phosphate (PLP, vitamin B6)

How is asparagine synthesized?

By amidation of aspartate

What enzyme synthesizes asparagine?

Asparagine synthetase

What are the reactants for asparagine synthesis?

Aspartate + Glutamine + ATP

What are the products of asparagine synthesis?

Asparagine + Glutamate + AMP + PPi

Key difference between aspartate and asparagine synthesis?

• Aspartate: formed by transamination

• Asparagine: formed by amidation using glutamine

What is the difference between essential and nonessential amino acids?

• Essential: cannot be synthesized → must come from diet

• Nonessential: can be synthesized by the body

How many amino acids can humans synthesize?

About half (nonessential amino acids)

Which organisms can synthesize all 20 amino acids?

plants and microbes

List the essential amino acids in humans

Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine

List the nonessential amino acids

Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine, Tyrosine

How is alanine synthesized?

Transamination of pyruvate

How is aspartate synthesized?

Transamination of oxaloacetate

How is asparagine synthesized?

From aspartate + glutamine (NH₃ donor)

How is glutamate synthesized?

Transamination of α-ketoglutarate

How is glutamine synthesized?

From glutamate + NH₃ via glutamine synthetase

How is cysteine synthesized?

From serine + methionine (provides sulfur)

How is tyrosine synthesized?

From phenylalanine

What are the main metabolic “starting points” for amino acid synthesis?

• Pyruvate

• Oxaloacetate

• α-ketoglutarate

• 3-phosphoglycerate

What is the common reaction type for many amino acids?

Transamination (using glutamate)

What is the main nitrogen donor in amino acid synthesis?

Glutamate (directly) or glutamine (for NH₃ transfer)

What two key components are required for amino acid synthesis?

Carbon backbone + nitrogen source

Where do carbon backbones for amino acids come from?

• Glycolysis

• Citric acid cycle

• Pentose phosphate pathway

Which glycolysis intermediates serve as carbon skeletons?

• 3-phosphoglycerate

• Phosphoenolpyruvate (PEP)

• Pyruvate

Which citric acid cycle intermediates are used for amino acid synthesis?

• Oxaloacetate

• α-ketoglutarate

Which pentose phosphate pathway intermediates are used?

• Ribose-5-phosphate

• Erythrose-4-phosphate

What provides the nitrogen for amino acid synthesis?

NH₄⁺ (ammonia)

Which molecules deliver nitrogen (NH₄⁺) in amino acid synthesis?

Glutamate and glutamine

Which molecule is the main amino group donor in transamination?

Glutamate

Which molecule donates free ammonia (NH₃) in biosynthesis reactions?

Glutamine

What happens to amino acids when they are degraded?

• Nitrogen → NH₄⁺ → urea

• Carbon skeleton → α-keto acids

What happens to the carbon skeleton (α-keto acids) after amino acid degradation?

• Enter the citric acid cycle

• Used for energy or glucose production

What happens to nitrogen removed from amino acids?

Converted to urea for excretion

What cycle is responsible for nitrogen excretion?

Urea cycle

How are amino acid metabolism and the citric acid cycle connected?

Through α-keto acid intermediates

Why is ammonia (NH₄⁺) toxic?

It disrupts cellular metabolism and must be converted to urea

What are the two major sources of amino acids for catabolism?

Dietary proteins and intracellular (body) proteins

What is the first step in amino acid catabolism?

Removal of nitrogen (deamination/transamination)

What happens to amino acid carbon skeletons after nitrogen removal?

They become α-keto acids

Where do α-keto acids go in metabolism?

• Citric acid cycle (energy production)

• Gluconeogenesis (glucose formation)

• Ketogenesis (ketone bodies)

• Lipid synthesis (fatty acids)

How are amino acids linked to energy production?

Their carbon skeletons enter the citric acid cycle for ATP production

How are amino acids linked to glucose production?

Carbon skeletons can be converted into glucose via gluconeogenesis

Which amino acids are glucogenic?

Those that form intermediates that enter the citric acid cycle or gluconeogenesis

Which amino acids are ketogenic?

Those that form acetyl-CoA or acetoacetyl-CoA

What do acetyl-CoA and acetoacetyl-CoA form?

Ketone bodies

When are ketone bodies produced from amino acid breakdown?

During low glucose availability (fasting/starvation)

What other major biomolecules can amino acid carbon skeletons become?

Fatty acids (via acetyl-CoA)

Where does the urea cycle occur?

liver

What is the central metabolic hub of amino acid catabolism?

Citric acid cycle

What are the three major metabolic fates of amino acid carbon skeletons?

• Glucose (gluconeogenesis)

• Fatty acids (lipogenesis)

• Ketone bodies (ketogenesis)

What connects amino acid metabolism to carbohydrate and fat metabolism?

Acetyl-CoA and citric acid cycle intermediates

where are the amino acids that are catabolized coming from?

released from degradation of cellular proteins or ingested from dietary proteins and degraded down in the stomach or small intestine

absorbed by the intestinal cells and transported in the blood to the tissues

How are dietary proteins digested?

By proteases in the GI tract

Which enzyme digests proteins in the stomach?

Pepsin