AA4 Nitrogen Metabolism

What are the three major sources of amino acids in humans?

(1) Dietary protein digestion

(2) Intracellular protein degradation

(3) De novo synthesis (nonessential amino acids).

What are the two main fates of amino acids?

(1) Used for protein synthesis and biosynthesis of nitrogen-containing compounds

(2) Catabolized for energy.

What happens to excess amino acids that are not needed for protein synthesis?

Their carbon skeletons are oxidized for energy or converted to glucose/fat, and their nitrogen is excreted as urea.

What reaction removes the amino group from an amino acid?

Transamination.

What coenzyme is required for transamination reactions?

Pyridoxal phosphate (PLP), derived from vitamin B₆.

What enzyme catalyzes the transfer of amino groups?

Aminotransferase (transaminase).

What is the product of oxidative deamination?

α-keto acid and free ammonia (NH₃/NH₄⁺).

Why must ammonia be converted into urea?

Ammonia is highly toxic, especially to the brain.

Which organ converts toxic ammonia into urea?

The liver.

Which amino acid carries nitrogen from muscle to the liver?

Alanine (via the glucose–alanine cycle).

Which amino acid serves as the main nitrogen donor in transamination reactions?

Glutamate.

Which amino acid transports ammonia safely in the bloodstream?

Glutamine.

Which amino acid donates nitrogen to form urea?

Aspartate.

What are the two main intracellular protein degradation systems?

Lysosomal pathway and ubiquitin–proteasome pathway.

What is the function of lysosomes in protein degradation?

Digest membrane and extracellular proteins via autophagy.

What is the function of the ubiquitin–proteasome system?

Degrades misfolded or short-lived cytosolic proteins.

What is ubiquitination?

The process of tagging proteins with ubiquitin for degradation.

What are the three key enzymes in ubiquitination and their roles?

• E1: Activates ubiquitin

• E2: Conjugates ubiquitin

  • E3: Ligates ubiquitin to target protein

What happens to a protein after it is polyubiquitinated?

It is degraded by the proteasome into peptides and amino acids.

Why must dietary proteins be hydrolyzed before absorption?

Whole proteins are immunogenic and cannot cross the intestinal barrier intact.

What enzyme begins protein digestion in the stomach?

Pepsin (active form of pepsinogen).

What hormone triggers the release of gastric acid and pepsinogen?

Gastrin.

What is a zymogen?

An inactive enzyme precursor that must be activated (e.g., pepsinogen → pepsin).

How is pepsinogen activated?

Low pH in the stomach causes self-cleavage (autocatalysis) into pepsin.

What happens when acidic chyme enters the small intestine?

Secretin stimulates the pancreas to release bicarbonate and digestive zymogens.

Name the major pancreatic proteases and their activation cascade.

• Trypsinogen → Trypsin (by enteropeptidase)

  • Trypsin activates: Chymotrypsinogen, Proelastase, Procarboxypeptidase.

What are the cleavage specificities of each enzyme?

• Trypsin: after Lys or Arg

• Chymotrypsin: after aromatic residues

• Elastase: small neutral residues

  • Carboxypeptidase: cleaves amino acids from C-terminal end

Where does amino acid absorption occur?

In the small intestine (via transporters in microvilli).

Where do absorbed amino acids go first?

To the liver via the portal circulation.

What are essential amino acids?

Amino acids that cannot be synthesized by humans and must come from the diet (9 total).

What are nonessential amino acids?

Amino acids that can be synthesized by the body from metabolic intermediates.

Name three conditionally essential amino acids and their dependencies.

Arginine – required during growth/pregnancy

Tyrosine – depends on phenylalanine

Cysteine – depends on methionine

What is protein turnover?

The balance between protein synthesis and degradation to maintain protein homeostasis.

Why is protein turnover important?

It allows removal of damaged proteins, regulation of enzyme levels, and adaptation to metabolic needs.

How do cells decide which proteins to degrade?

Based on N-terminal residue signals or ubiquitin tagging.

Transamination

Transfer of an amino group between amino acids and keto acids

Oxidative deamination

Removal of an amino group to release ammonia

α-Ketoglutarate

Common amino group acceptor in transamination

Glutamate dehydrogenase

Enzyme that converts glutamate to α-ketoglutarate and NH₄⁺

Ammonia assimilation

Incorporation of ammonia into organic molecules (via glutamine synthetase)

Urea cycle

Pathway that converts toxic ammonia into urea for excretion

Enteropeptidase

Enzyme in the intestine that activates trypsinogen to trypsin

When are amino acids catabolized?

• During protein turnover (when amino acids are not reused)

• After ingestion of excess dietary protein

• During fasting, starvation, or energy demand (amino acids used for ATP)