Urea Biosynthesis and Amino Acid Metabolism Pathways

Control of Urea Biosynthesis

Reaction: CO₂ + NH₄⁺ + 4ATP + Asp → urea + fumarate + 4ADP + 2Pi + PPi

• Long-term regulation: Diet rich in protein or starvation upregulates urea cycle enzymes.
• Short-term regulation: N-acetylglutamate activates arginine synthetase, stimulating urea production.

Amino Acid Catabolism Pathways

• Gluconeogenic (Pyruvate): [Ala, Ser, Gly, Cys, Thr, Trp] → Pyruvate
• Gluconeogenic (Oxaloacetate): [Asp, Asn] → Oxaloacetate
• Gluconeogenic (α-Ketoglutarate): [Glu, Gln, Pro, Arg, His] → α-Ketoglutarate
• Gluconeogenic (Succinyl-CoA): [Val, Met, Ile, Thr] → Succinyl-CoA
• Gluconeogenic (Fumarate): [Phe, Tyr] → Fumarate
• Ketogenic (Acetyl-CoA): [Leu, Lys] → Acetyl-CoA
• Glucoketogenic: [Trp, Ile, Thr, Tyr, Phe]

Biogenic Amines by Decarboxylation of Amino Acids

• Glutamate + Glutamate Decarboxylase (PLP, -CO₂) → GABA
• Histidine + Decarboxylase (PLP, -CO₂) → Histamine
• Tryptophan + Tryptophan Hydroxylase → 5-Hydroxytryptophan + Decarboxylation (PLP, -CO₂) → Serotonin

Nitrogen Compounds of Interest

• Tyrosine: Thyroid hormones (T3, T4)
• Tryptophan: Plant hormones (auxins)
• Serine: Neurotransmitters (Acetylcholine)
• Methionine and Ornithine: Polyamines
• Nucleotide Bases: Purines and Pyrimidines

Amine Biosynthesis of Catecholamines

Tyrosine + O₂ → L-Dopa → (Decarboxylation, -CO₂) → Dopamine → (Hydroxylase + Ascorbic Acid) → Norepinephrine → (Methylation + SAM) → Epinephrine

Creatine and Phosphocreatine Biosynthesis

Arginine + Glycine → Creatine + ATP (Creatine Kinase) → Phosphocreatine + ADP

Glutathione Biosynthesis and Utilization

Glutamate + Cysteine + ATP → γ-Glutamylcysteine + Glycine + ATP → Reduced Glutathione.

Utilization of Glutathione

1. Coenzyme of glutathione peroxidase in the destruction of peroxides.
2. Antioxidant function for hemoglobin Fe³⁺ (reduced by NADPH + H⁺).

Glycine as a Precursor of Porphyrins

Occurs primarily in bone marrow and liver (85%). Glycine + Succinyl-CoA → Aminolevulinate → Porphobilinogen → Protoporphyrin IX + Fe²⁺ → Heme + Globin → Hemoglobin, Myoglobin, and Cytochromes.

Degradation of Heme

Heme + Oxygen → Biliverdin + Fe³⁺ + CO → Bilirubin + Glucuronic Acid → Conjugated Bilirubin → Urobilin / Stercobilin.

Congenital Porphyrias

• Congenital Erythropoietic Porphyria: Uroporphyrinogen III cosynthase deficiency; accumulation of erythrocyte uroporphyrinogen derivatives causing red urine, skin photosensitivity, and hypertrichosis.
• Acute Intermittent Porphyria: Hepatic uroporphyrinogen synthase deficiency; excretion of ALA and porphobilinogen, causing red urine, abdominal pain, and neurological dysfunction.

Non-Essential Amino Acid Biosynthesis

• Glycolytic family (Pyruvate, Phosphoglycerate): Alanine, Serine, Glycine
• Citric Acid Cycle family (α-Ketoglutarate, Oxaloacetate): Proline, Glutamine, Glutamate, Aspartate, Asparagine