MN14 - Nitrogen Metabolism

What is the amino acid pool?

The amino acid pool is the total amount of free amino acids available in the body from dietary intake, protein turnover, and de novo synthesis.

What are the sources of the amino acid pool?

Dietary proteins (70-100 g/day), turnover of endogenous proteins (~400 g/day), and de novo synthesis of nonessential amino acids.

What are the uses of the amino acid pool?

Replenishment of body proteins, synthesis of biomolecules (nucleotides, neurotransmitters, creatine), and energy production.

What happens to glucogenic amino acids?

They are converted into glucose or glycogen.

What happens to ketogenic amino acids?

They are converted into fatty acids or ketone bodies.

Do amino acids have a storage form?

No, there is no storage form for amino acids.

What is nitrogen metabolism input?

Amino acids from dietary and endogenous sources.

What happens to nitrogen in the body?

Nitrogen has no storage form and is either reused or excreted.

How is nitrogen reused?

Used to form proteins, nucleotides, and biological amides.

How is nitrogen excreted?

Mainly as urea (~85%) and also as ammonia.

What is nitrogen balance?

Nitrogen balance is the difference between nitrogen intake and nitrogen excretion.

What does positive nitrogen balance indicate?

Greater nitrogen intake than loss, seen in growth, pregnancy, recovery, and anabolic states.

What does nitrogen equilibrium indicate?

Equal nitrogen intake and loss, seen in healthy adults.

What does negative nitrogen balance indicate?

Greater nitrogen loss than intake, seen in illness, trauma, or malnutrition.

What are the excretory forms of nitrogen in humans?

Urea (major), ammonia (NH4+), and small amounts of uric acid.

What type of organism are humans in terms of nitrogen excretion?

Ureotelic (excrete nitrogen mainly as urea).

What is the main nitrogen source in amino acid metabolism?

The α-amino group.

Why must ammonia be detoxified?

Free ammonia is toxic, especially to the brain.

What are the three major steps of amino group metabolism?

Transamination, oxidative deamination, and urea synthesis.

What is transamination?

Transfer of an α-amino group from an amino acid to an α-keto acid.

Where does transamination occur?

Cytoplasm of all cells.

What enzymes catalyze transamination?

Aminotransferases (transaminases).

What coenzyme is required for transamination?

Pyridoxal phosphate (PLP), derived from vitamin B6.

What is the common amino group acceptor?

α-ketoglutarate (forms glutamate).

What does ALT do?

Alanine aminotransferase converts alanine to pyruvate.

What does AST do?

Aspartate aminotransferase converts aspartate to oxaloacetate.

What is the clinical significance of ALT and AST?

Elevated levels indicate tissue damage.

What does elevated ALT suggest?

Liver damage (e.g., hepatitis, toxic injury).

What does elevated AST suggest?

Muscle damage (e.g., myocardial infarction).

What is oxidative deamination?

Removal of an amino group from glutamate to release ammonia (NH4+).

Where does oxidative deamination occur?

Mitochondrial matrix of hepatocytes (less in kidney).

What enzyme catalyzes oxidative deamination?

Glutamate dehydrogenase (GDH).

What cofactors are required for GDH?

NAD+ or NADP+.

How is GDH regulated?

Inhibited by high ATP; stimulated by high ADP/AMP.

What are sources of ammonia in the body?

Glutamate deamination, glutamine breakdown, purine/pyrimidine metabolism, and intestinal bacteria.

What is the main fate of ammonia?

Converted to urea for excretion (~80%).

What is the role of glutamine in ammonia metabolism?

It transports ammonia safely in a non-toxic form.

What enzyme forms glutamine?

Glutamine synthetase.

What enzyme releases ammonia from glutamine?

Glutaminase.

What are the two mechanisms for ammonia transport to the liver?

Glutamine shuttle and glucose-alanine cycle.

What is the glutamine shuttle?

Ammonia is incorporated into glutamine, transported to the liver, and released as ammonia for urea synthesis.

What is the glucose-alanine cycle?

Alanine transports nitrogen from muscle to liver, where it is converted back to pyruvate for gluconeogenesis.

Where does the glucose-alanine cycle primarily occur?

Skeletal muscle and liver.

What is the urea cycle?

The main pathway for nitrogen disposal converting toxic ammonia into urea.

Where does the urea cycle occur?

Liver; begins in mitochondrial matrix and continues in cytosol.

What are the sources of nitrogen in urea?

One nitrogen from ammonia and one from aspartate.

What is the carbon source of urea?

Bicarbonate (HCO3-).

What is the rate-limiting step of the urea cycle?

Carbamoyl phosphate synthesis by CPS-I.

What enzyme catalyzes this step?

Carbamoyl phosphate synthetase I (CPS-I).

What does CPS-I require?

2 ATP.

What activates CPS-I?

N-acetylglutamate.

What regulates N-acetylglutamate production?

Arginine.

What happens in CPS-I deficiency?

Hyperammonemia causing brain damage, coma, and death.

What happens in citrulline synthesis?

Ornithine combines with carbamoyl phosphate to form citrulline.

How is citrulline transported?

Exported to cytosol in exchange for ornithine.

What happens in argininosuccinate synthesis?

Citrulline condenses with aspartate to form argininosuccinate.

What does this step require?

1 ATP.

What happens in ASS deficiency?

Citrullinemia causing neurological impairment.

What happens in arginine synthesis?

Argininosuccinate is cleaved into arginine and fumarate.

What is the fate of fumarate?

Converted to malate then oxaloacetate, which can form aspartate or be used in gluconeogenesis.

What happens in urea production?

Arginine is hydrolyzed to ornithine and urea by arginase.

Where is arginase expressed?

Only in the liver.

What happens to urea?

It enters blood, is filtered by kidneys, and excreted in urine.

What is hyperammonemia?

Elevated blood ammonia due to impaired detoxification.

What are causes of hyperammonemia?

Genetic enzyme defects or liver disease (hepatitis, cirrhosis).

What are symptoms of hyperammonemia?

Vomiting, lethargy, poor cognition, coma, and death.

How is hyperammonemia treated?

Low-protein diet and pharmacologic therapy.