Protein Degradation and Tissue Utilization of Amino Acids

Question 1

When is nitrogen balance positive?

Answer 1

During growth, from infancy to adolescence, pregnancy, lactation, during recovery from illness or malnutrition

Question 2

When is nitrogen balance negative?

Answer 2

Illness or malnutrition

Question 3

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

Answer 3

Hartnup disease (Autosomal recessive)

Question 4

What are the three basic amino acids?

Answer 4

Ornithine, Arginine, Lysine

Question 5

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

Answer 5

Cystinuria (autosomal recessive)

Question 6

What are the treatments for cystinuria

Answer 6

High fluid intake, medications that elevate urine pH

Question 7

What are the treatments for Hartnup disease?

Answer 7

Treatments include niacin-rich diet, high protein diet (increases the amount of dipeptides that can be taken up)

Question 8

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

Answer 8

Lysinuric protein intolerance (autosomal recessive)

Question 9

What are the treatments for lysinuric protein intolerance?

Answer 9

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

Question 10

What uses the ubiquitin-proteasome degradation pathway?

Answer 10

Misfolded/damaged intracellular proteins

Turnover of intracellular proteins (i.e., myosin degradation or degradation of transcription factors)

Question 11

What ion is involved in activating metalloproteinases?

Answer 11

Zinc

Question 12

What is the name for the major lysosomal proteases?

Answer 12

Cathepsins

Question 13

Which ubiquitin ligase complex will determine which protein will be ubiquitylated?

Answer 13

E2 and E3

Question 14

What is CAP used for? Why is ATP important in proteasomes? What is it not used for?

Answer 14

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

Question 15

What is the action of Bortezomib (Velcade)?

Answer 15

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

Question 16

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

Answer 16

Angelman Syndrome (non-Mendelian, genomic imprinting)

Question 17

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

Answer 17

Von Hippel-Lindau syndrome (autosomal dominant, two hit hypothesis)

Question 18

Where is most of the body’s amino acid stored?

Answer 18

No specialized storage, most are stored dynamically in functional proteins. However, most of the body’s supply are found in skeletal muscles

Question 19

Where are proteins degraded to amino acids?

Where are they turned into glucose and ketone bodies?

What is the major glucogenic amino acid?

Answer 19

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

Question 20

How are amino acids transported across the BBB? Which amino acids are transported?

Answer 20

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

Question 21

Where are intestinal enzymes activated? What activates them?

Answer 21

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