Chapter 23: Protein Turnover & Amino Acid Catabolism

Urea Cycle

A metabolic cycle in the liver that disposes of excess N by converting it to urea. The N atoms in urea come from NH₄⁺, HCO₃⁻, & the α-NH2⁺ groups of Glu & Asp. The cycle releases 2N & 1C atoms per turn & is linked to the TCA cycle through fumarate.

A-Ketoglutarate Family

Amino Acids that are synthesized from A-KG, a TCA intermediate. Glutamate acts as the primary N donor for other biosynthetic pathways through aminotransferase reactions. Proline & Ornithine share similarities in their synthetic pathways.

Aspartate Family

Amino Acids that are synthesized from oxaloacetate (OAA). Transamination of OAA produces Asp; amidation produces Asn. β-aspartyl semialdehyde & homoserine are key branch points for Met, Thr, & Lys biosynthesis. Met is a key methyl donor via S-adenosylmethionine.

Pyruvate Family

Alanine is formed by transamination of pyruvate while valine & leucine are synthesized from α-keto acids derived from pyruvate. Their biosynthesis involves multiple steps including transamination, & resembles Isoleucine biosynthesis from Threonine.

3-Phosphoglycerate Family

Ser is synthesized by diverting 3-PG from glycolysis. It is then transaminated to 3-phosphoserine, dephosphorylated to Ser, & can be converted to Gly via Serine hydroxymethyltransferase (PLP-dependent, transfers a C to THF). Cys synthesis also involves PLP.

Erythrose-4-Phosphate & Phosphoenolpyruvate Family

Synthesized via the shikimate pathway, starting from PEP & Erythrose-4-P. Chorismate is a key branch point. Trp synthesis involves “channeling” by tryptophan synthase. His is synthesized from PRPP but is often grouped here for convenience.

Ubiquitin

A small protein that marks other proteins for degradation. Proteins are tagged when they are damaged, misfolded, or no longer needed. This tagging is part of regulated protein turnover, which controls metabolism & cell division. It’s pathway inhibition is a target for cancer therapy.

Histidine Family

Synthesized from PRPP (phosphoribosyl pyrophosphate), & although it shares intermediates with purine biosynthesis, its pathway is distinct. It’s biosynthesis is considered part of its own family due to the unique use of PRPP & connection to nucleotide metabolism.

Ketogenic Amino Acids

Amino acids that are broken down into acetyl-CoA or acetoacetate, which are precursors for ketone bodies.

Glucogenic Amino Acids

Amino acids that are broken down into pyruvate or TCA cycle intermediates such as α-ketoglutarate, succinyl-CoA, fumarate, or oxaloacetate, which can be used in gluconeogenesis to make glucose.

Aminotransferase

Enzymes that transfer amino groups between an amino & a keto acid, especially using Glu as the N donor. They are essential for both amino acid biosynthesis & degradation & require the cofactor PLP (pyridoxal phosphate).

Proteosome

A multi-subunit protein complex that degrades ubiquitin-tagged proteins into peptides, which regulates protein levels, removes misfolded proteins, & plays a major role in cellular homeostasis. Their inhibitors are used as cancer drugs & antibiotics.

Porphyrins

Cyclic compounds that are precursors to heme, an essential component of hemoglobin & cytochromes. Disorders in its synthesis can lead to neurological symptoms & photosensitivity.

Cirrhosis

A chronic liver disease often caused by alcohol abuse, hepatitis, or metabolic disorders. It can impair the liver's ability to perform the urea cycle, leading to accumulation of toxic nitrogenous compounds like ammonia.