Amino Acid Degradation and Metabolism

Amino Acid Degradation

• Amino acid degradation results in ammonium (NH4+) and carbon skeletons.
• NH4+ can be converted into nitrogen-containing compounds like nucleotides or excreted as urea.
• Carbon skeletons can enter TCA cycle intermediates for ATP production, fatty acid synthesis, or gluconeogenesis.

Functions of Amino Acids

• Certain amino acids act as neurotransmitters, including glycine, aspartate, and glutamate.
• The body contains approximately 100g of free amino acids as an amino acid pool.
• Glutamate and glutamine make up about 50% of the amino acid pool; essential amino acids account for around 10%.
• Intracellular amino acid concentration exceeds that of extracellular; cellular uptake occurs against a concentration gradient.

Sources and Turnover of Amino Acids

• The amino acid pool is maintained through dietary protein intake and synthesis of non-essential amino acids.
• Body protein turnover involves 300-400g of protein being constantly degraded and synthesized daily.

Essential and Nonessential Amino Acids

• Essential amino acids must be obtained through diet; they have more complex structures and require numerous enzymatic reactions for synthesis.
• Conditional essential amino acids include tyrosine (derived from phenylalanine) and arginine (partially synthesized from argininosuccinate).

Transamination Mechanism

• Transamination involves transferring the amino group from an amino acid to an α-keto acid, producing a new amino acid and a keto acid.
• The process utilizes pyridoxal phosphate (PLP) as a coenzyme, facilitating amino group transfer.

Transamination and Deamination

• Transamination occurs in the cytoplasm, converting amino acids while transporting amino groups as glutamic acid to the liver.
• Deamination removes an amino group from amino acids as NH3, contributing to urea synthesis from liberated ammonia.

Glutamate Dehydrogenase (GDH)

• GDH, found in liver mitochondria, converts glutamate to α-ketoglutarate and ammonia.
• GDH is regulated allosterically, activated by ADP and inhibited by GTP.

Urea Cycle

• Urea is synthesized in the liver and transported to kidneys for excretion, comprising two nitrogen atoms from ammonia and aspartic acid.
• The urea cycle consists of five steps involving specific enzymes; initial steps occur in mitochondria while the latter steps take place in the cytosol.

Enzyme Regulation and Deficiencies

• Carbamoyl phosphate synthetase I (CPS I) initiates urea production by converting NH4+ and CO2 into carbamoyl phosphate, requiring N-acetylglutamate for activity.
• Disorders of urea metabolism lead to hyperammonaemia, resulting from inherited or acquired enzyme deficiencies.

Methionine Metabolism

• Methionine is vital for epigenetic regulation and cysteine production, influencing gene expression through methylation processes.

Phenylketonuria (PKU)

• PKU is an autosomal recessive disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to mental retardation and other symptoms.
• An early 20th-century case study identified the condition, originally named 'imbecillitas phenylpyruvica.'
• Management involves a strict low-protein diet to mitigate symptoms and improve health outcomes.

This quiz explores the processes involved in amino acid degradation, focusing on the production of ammonium and carbon skeletons. It covers their roles in synthesizing nitrogen-containing compounds and generating ATP, highlighting their importance in metabolism and energy production.