Biochem 13.2 Protein Catabolism Overview

Protein Catabolism

• Proteins are not the primary energy source for most organisms, but are important for biological roles like enzymes and structure
• Proteins are broken down into individual amino acids for energy or to synthesize new proteins needed by the body
• Protein digestion starts with breaking down proteins into smaller peptides or amino acids in the digestive tract, using enzymes like pepsin, trypsin, chymotrypsin, and carboxypeptidase
• Short peptides are further broken down into amino acids in the intestinal cells. These amino acids are absorbed into the bloodstream and transported to body tissues for incorporation into needed proteins
• Proteins are degraded when no longer needed, misfolded, or when the cell needs the amino acids for other uses
• Proteins within the cell may be tagged for degradation by ubiquitin and targeted to the proteasome for rapid breakdown
• Lysosomes may degrade proteins from other organelles or the surrounding environment through endocytosis
• After digestion, the individual amino acids may be recycled, or further digested for energy

Transamination, Deamination, and Deamidation

• Transamination is the first step in amino acid catabolism, where the amino group of an amino acid is transferred to another molecule (like α-ketoglutarate)
• This converts the amino acid into an α-keto acid, which has a ketone group where the amino group was
• α-Ketoglutarate becomes glutamate when it receives the amino group
• Several α-keto acids are important: pyruvate (alanine), oxaloacetate (aspartate), and α-ketoglutarate (glutamate) are related to the citric acid cycle, enabling entry into energy pathways
• Other amino acids can undergo transamination directly or other associated pathways
• In the liver, glutamate is deaminated to regenerate α-ketoglutarate, and release ammonia (NH4+) for the urea cycle
• In cells without the urea cycle, NH4+ can be toxic; instead, glutamate is converted to glutamine, a less toxic carrier molecule

The Urea Cycle

• Once in the liver, glutamate and glutamine release ammonium ions, which enter the urea cycle for processing
• The urea cycle processes nitrogen from amino acids into urea, a non-toxic waste product excreted through the kidneys, removing toxic byproducts.
• Urea cycle involves reactions in the mitochondria and cytosol. A crucial aspect of the cycle is that it requires ATP and converts ammonia to urea.
• The urea cycle and the citric acid cycle share intermediates, allowing for a connection between protein metabolism and energy production
• Defects in the urea cycle can lead to severe metabolic disorders and dangerous buildup of ammonia

Glucogenic and Ketogenic Amino Acids

• After losing nitrogen, amino acids leave behind different carbon skeletons which are metabolized through distinct pathways
• Amino acids may be glucogenic (generate glucose), ketogenic (generate ketone bodies) or both. This classification is based on the way the carbon skeleton is processed
• Glucogenic amino acids' carbon skeletons are converted to pyruvate or a citric acid cycle intermediate, crucial for gluconeogenesis
• Pyruvate forms oxaloacetate for gluconeogenesis, and citric acid intermediates can be converted to oxaloacetate
• Ketogenic amino acids' carbon skeletons are converted into acetyl-CoA or acetoacetyl-CoA, precursors for ketone bodies.
• Catabolism may lead to both glucogenic and ketogenic products from one amino acid. Examples include tryptophan, phenylalanine, tyrosine, isoleucine, and threonine. Importantly, the processing of carbon skeletons from these amino acids is quite complex.