What percentage of protein is turned over in our body every day?
5-10%
What is the DRI for protein for adults?
0.8 g/kg/day (56 g/day for a man, 44 g/day for a woman)
What is Cachexia?
- Loss of weight, muscle atrophy, fatigue, weakness and loss of appetite
- accompanies cancer, AIDS, CHF, or major trauma
- cannot be reversed nutritionally
- appears to be a response to inflammatory cytokines –> ubiquitin-proteosome pathway and inhibition of protein synthesis
How do we measure protein insufficiency? Why?
Serum protein transthyretin (prealbumin), because it has a high turnover (half life 1-2 days) for a serum protein
Which two AAs are used to transport nitrogen in the blood?
Alanine and Glutamine
Which enzyme shuttles amino groups between AAs?
aminotransferases/transaminases
What is the cofactor for aminotransferase?
Pyridoxal phosphate (derived from B6).
What enzyme is used to synthesize non-essential AAs from glutamate?
transaminse/aminotransferase
Describe the movement of nitrogen from skeletal muscle to the liver via transaminase.
- Transaminase: a-ketoglutarate + AA –> glutamate + a-keto acid
- ALT (alanine transaminase):glutamate + pyruvate –> a-ketoglutarate + alanine
- alanine –> liver
Describe what happens to alanine once it reaches the liver.
- ALT (alanine transaminase): alanine + a-ketoglutarate –> glutamate + pyruvate
- pyruvate –> glucose, glycogen, FAs (or oxidized for energy)
- glutamate –> urea cycle
Describe the movement of nitrogen from peripheral tissue to the liver/kidney via glutamine synthetase.
- glutamine synthetase: glutamate + NH4+ –> glutamine
- glutamine –> liver/kidney
- glutaminase: glutamine –> glutamate + NH4+
Describe the entry of glutamate into the urea cycle.
glutamate dehydrogenase: glutamate –> a-ketoglutarate + NH4+
(bidirectional enzyme. Uses NAD+ in catabolic reaction and NADP+ in anabolic reaction)
What is the overall reaction for urea synthesis?
NH3 + HCO3- + aspartate + 3ATP –>
urea + fumarate + 2ADP + 4Pi
Which AA donates a nitrogen to urea?
Aspartate
How many high energy bonds are used in the formation of one molecule of urea?
4
What is the significance of N-acetylglutamate (NAG)?
It is an absolute requirement for carbomoyl phosphate synthetase.
Draw the urea cycle.
Well..?
What happens to fumarate after it is formed in the urea cycle?
It is converted to oxaloacetate by the TCA cycle enzymes –> NADH.
List 3 ways the urea cycle is regulated.
- substrate availability
- the synthesis of urea cycle is induced under conditions of a high protein diet or in prolonged fasting.
- N-acetylglutamate is only synthesized when glutamate and acetyl-CoA levels are high. Arginine is a positive allosteric regular of NAGS.
