Amino Acids and The Urea Cycle

Understand the importance of the nitrogen cycle

The atmosphere is 80% N2 gas, which must be converted ("fixed") into a usable form like ammonia (NH3). This usable nitrogen is essential for all life, as it's a component of nucleic acids (DNA/RNA), proteins, hormones, etc.

Explain nitrogen fixation, and how ammonia is incorporated into proteins.

The process of converting N2 to 2NH3. This is done by the nitrogenase enzyme complex in some bacteria (often in legume root nodules). It is a very energy-intensive process (requires 16 ATP). Incorporation: Ammonia (NH₃) is first incorporated into glutamate (using ATP) to form glutamine. Glutamine then acts as the primary nitrogen donor for building other amino acids and biomolecules.

Recall the sources of amino acids from glycolysis and the citric acid cycle

Glycolysis: 3-Phosphoglycerate, Phosphoenolpyruvate, Pyruvate. Citric Acid Cycle (CAC): alpha-Ketoglutarate, Oxaloacetate.

Recall that glutamine is the source of nitrogen for amino acid biosynthesis

Glutamine (and glutamate) is the primary source of nitrogen. Glutamine transfers its amino group (NH2) to other substrates via amidotransferase enzymes

Know the purpose of the shikimate pathway

A metabolic pathway (not in humans) that produces the aromatic amino acids (phenylalanine, tyrosine, tryptophan) and many natural products (spices, alkaloids).

Understand how amino acid biosynthesis is regulated

It is regulated by allosteric feedback inhibition, where the final product amino acid binds to and inhibits an enzyme earlier in its own synthesis pathway.

Explain how amino acid inhibitors function, and know asparaginase and glyphosate

They block key enzymes in the synthesis pathway. Asparaginase: Degrades asparagine in the blood (used against leukemia). Glyphosate (Roundup): Inhibits an enzyme in the shikimate pathway in plants.

Understand heme biosynthesis, and the source molecules

Heme biosynthesis begins in the mitochondria from two source molecules: Glycine and Succinyl-CoA, which react to form sigma-aminolevulinic acid.

Understand how defects in heme biosynthesis can cause disease

Genetic defects cause porphyrias. Metabolic precursors accumulate, causing UV light sensitivity, red teeth, and neurological conditions.

Know the breakdown pathway of heme, and the intermediates and end products

Heme → Biliverdin (green) → Bilirubin (yellow) → Conjugated in liver → Excreted in bile → Broken down in intestine to Urobilin (urine color) or Stercobilin (feces color).

State the cause and effects of jaundice

Cause: Accumulation of bilirubin in the blood due to impaired liver function, blocked bile ducts, or insufficient processing enzymes (common in newborns). Effects: Yellowish pigmentation of the skin and eyes

Describe the source and function of creatine

Source: Made from Glycine, Arginine, and Methionine. Function: Converted to phosphocreatine in muscle for rapid, anaerobic regeneration of ATP during heavy activity.

Describe the source and function of glutathione (GSH)

Source: Tripeptide (Glutamate, Cysteine, Glycine). Function: A major reducing agent/antioxidant that protects cells from oxidative damage.

Recall which neurotransmitters and hormones are amino acid derivatives

Tyrosine → Dopamine, Norepinephrine, Epinephrine.

Glutamate → GABA.

Tryptophan→ Serotonin.

Histidine → Histamine.

Arginine → Nitric Oxide (NO).

Explain the basic human dietary needs (percentages, grams/day)

Carbs: 45-65% (~300 g/day); Fat: 20-35%; Protein: 10-35% (~50 g/day).

Explain the problem with eating only lean protein

"Protein poisoning" or "rabbit starvation." Excess ammonia (NH3) from deamination can overwhelm the urea cycle, leading to the toxic buildup of ammonia in the blood (hyperammonemia).

Describe how amino acids are broken down and used for energy.

Proteins are broken into peptides by pepsin/trypsin and finally into amino acids. For energy, the amino group is removed (transamination), and the remaining carbon skeleton enters the citric acid cycle to be oxidized for ATP.

Recall how various animals excrete nitrogen

Ammonia (NH4+): Aquatic vertebrates. Urea: Terrestrial vertebrates (humans). Uric Acid: Birds and reptiles (water conservation

Explain the amino group removal

Transamination: An aminotransferase enzyme transfers the amino group from the amino acid to alpha-ketoglutarate, forming glutamate, which acts as the central collector for nitrogen.

Understand the role of the glucose-alanine cycle

In muscle, pyruvate is converted to alanine to carry nitrogen to the liver. In the liver, alanine is converted back to pyruvate (for gluconeogenesis to make glucose) and the nitrogen goes to the urea cycle.

Define glucogenic and ketogenic

Glucogenic: Amino acids whose carbon skeletons are degraded to intermediates that can be used to synthesize glucose (e.g., pyruvate, oxaloacetate). Ketogenic: Amino acids degraded to acetyl-CoA or acetoacetyl-CoA, which can form ketone bodies or fats (e.g., Leucine, Lysine).

State the cause of phenylketonuria (PKU)

A deficiency in the enzyme phenylalanine hydroxylase, which prevents the conversion of phenylalanine to tyrosine, leading to the toxic buildup of phenylalanine and impaired neurological development

Explain the purpose of the urea cycle, and where it occurs in the cell

To convert toxic ammonia (NH4+) into the less toxic and water-soluble compound urea for excretion. Location: The first steps are in the mitochondria, and the rest are in the cytosol of liver cells.

Recall the source of urea’s nitrogens

One nitrogen comes from free ammonia, and the second nitrogen comes from the amino acid aspartate.

Recall the role of the aspartate-arginosuccinate shunt

It links the urea cycle and the citric acid cycle (CAC). Fumarate produced in the urea cycle is converted to oxaloacetate (in the CAC), which can then be converted to aspartate to provide the second nitrogen for the urea cycle.

Explain how the urea cycle is regulated

The first enzyme (Carbamoyl phosphate synthetase I) is allosterically activated by N-acetylglutamate. This signals that amino acid breakdown is active and ammonia needs to be processed