Protein Degradation and Tissue Utilization of Amino Acids Flashcards
When is nitrogen balance positive?
During growth, from infancy to adolescence, pregnancy, lactation, during recovery from illness or malnutrition
When is nitrogen balance negative?
Illness or malnutrition
Defect in the absorption of neutral amino acids (hydrophobic) at the brush border. Lack of tryptophan coupled with poor diet (niacin (vitamin B3) deficiency) can lead to pellagra-like symptoms. Tryptophan and vitamin B3 are both precursors for NAD+. Elevated neutral amino acids in urine. Symptoms include some photo-sensitivity, tremors, ataxia, nystagmus, but mostly normal clinically
Hartnup disease (Autosomal recessive)
What are the three basic amino acids?
Ornithine, Arginine, Lysine
Deficient brush border transport of COAL (Cystine, Ornithine, Arginine, Lysine — last three are basic amino acids). Symptoms include hyperaminoaciduria (of the involved amino acids), and cystine stones in kidney, ureter, and bladder
Cystinuria (autosomal recessive)
What are the treatments for cystinuria
High fluid intake, medications that elevate urine pH
What are the treatments for Hartnup disease?
Treatments include niacin-rich diet, high protein diet (increases the amount of dipeptides that can be taken up)
Deficient basal transport of basic amino acids (lysine, arginine, and ornithine). Symptoms include hyperaminoaciduria of the amino acids, low plasma levels of basic amino acids, secondary hyperammonemia after meals (due to inefficient urea cycle), and orotic aciduria
Lysinuric protein intolerance (autosomal recessive)
What are the treatments for lysinuric protein intolerance?
Treatments include intravenous arginine hydrochloride and oral citrulline to improve urea cycle. Nitrogen scavengers drugs to reduce blood ammonia concentrations, protein restricted, high calorie (carbohydrate, fat) diet
What uses the ubiquitin-proteasome degradation pathway?
Misfolded/damaged intracellular proteins
Turnover of intracellular proteins (i.e., myosin degradation or degradation of transcription factors)
What ion is involved in activating metalloproteinases?
Zinc
What is the name for the major lysosomal proteases?
Cathepsins
Which ubiquitin ligase complex will determine which protein will be ubiquitylated?
E2 and E3
What is CAP used for? Why is ATP important in proteasomes? What is it not used for?
CAP proteins are required for the activity of the proteasome
ATP is important for the unfolding of the protein and threading it into the proteasome core
ATP is not necessary however, for the cleavage itself
What is the action of Bortezomib (Velcade)?
Proteasome inhibitor drug (binds to the catalytic site of the proteasome). It is used for the treatment of multiple myelomas and mantle cell lymphomas (diseases with elevated proteasome levels). Probably prevents the destruction of pro-apoptotic factors, which leads to cancer cell death
Neurological disorder caused by the mutation or deletion of the UBE3A gene that codes for the E3 subunit of a ubiquitin ligase. Symptoms include delayed development or mental retardation, speech impairment, happy demeanor, frequent laughing, movement and balance disorders, and seizures
Angelman Syndrome (non-Mendelian, genomic imprinting)
Deficiency in an E3 uniquitin ligase subunit (VHL) prevents the destruction of hypoxia inducible factor 1a (HIF1a), a transcription factor that promotes angiogenesis. Symptoms include angiomatosis, high incidence of tumors: hemangioblastomas (in CNS), renal cell carcinoma, pheochromocytoma (adrenal gland), and endolympathic sac tumors
Von Hippel-Lindau syndrome (autosomal dominant, two hit hypothesis)
Where is most of the body’s amino acid stored?
No specialized storage, most are stored dynamically in functional proteins. However, most of the body’s supply are found in skeletal muscles
Where are proteins degraded to amino acids?
Where are they turned into glucose and ketone bodies?
What is the major glucogenic amino acid?
Amino acids are degraded in the muscle
Amino acids are converted to glucose and ketone bodies in the liver
Alanine is the major glucogenic amino acid
How are amino acids transported across the BBB? Which amino acids are transported?
Amino acids are transported through the BBB by transporters, the most important ones are BBCAAs — phe, tyr, trp, his, which are important for synthesizing NTs/hormones in the brain
Where are intestinal enzymes activated? What activates them?
Activation of trypsinogen, chymotrypsinogen, proelastase, and procarboxypeptidases occur in the small intestine (duodenum)
Trypsinogen is activated by enteropeptidases and the enzymes that follow are activated by trypsin
