Amino Acid Metabolism Flashcards
What are the sources of free amino acids in the body?
Degradation of: ingested protein, biosynthesis of some (non-essential), and degradation of endogenous protein
Differentiate essential from non-essential amino acids
Essential: cannot be synthesized by the body- has to be eaten in the diet
Non-essential: amino acids that can be synthesized via other pathways. Does not have to be eaten
What are free amino acids used for?
Resynthesis of endogenous protein Precursors for the synthesis of other biomolecules Energy production (and amino group is excreted as urea in the process)
Is the biosynthesis of amino acids sufficient to allow net synthesis of protein?
No. If you don’t eat enough protein in your diet, you will eventually lose muscle mass
What are two pathways by which protein degradation occurs?
Lysosome and proteosome
What is the half life of a protein?
The range varies from minutes to days
What is the “turnover” of protein in an adult?
Adults degrade and resynthesize 2-3% (~300g) of their total body protein every day.
What happens to excess amino acids?
Excess amino acids are degraded, not stored.
What is the recommended dietary allowance for daily protein?
55g
55g of amino acids are degraded daily. What are they being used for?
Biosynthesis of purines, pyrimidines and porphyrins
Carbon skeletons: (used for energy)
What would happen if you ate a protein free diet?
You would lose muscle mass. The body requires 55g of protein per day, and thus you would break down muscle mass for an additional amino acid supply
Define nitrogen balance
Nitrogen ingested (protein) = nitrogen excreted (urea)
If you eat more protein, you pee out more urea
The degradation of amino involves what two processes? What is their role?
1) Removal of the nitrogen to form urea –> excretion for nitrogen balance
2) Degradation of the carbon skeletons –> energy production
What is the first step in the degradation of many amino acids?
transamination
Where does biosynthesis urea occur?
The liver
Describe transamination.
Although there are several different amino acid transaminases (aminotransferases), all of them under go the same basic process:
Transamination is the transfer of the amino group to alpha-ketoglutarate to form glutamate
What cofactor is required for transaminases?
Pyridoxal phosphate- a derivative of vitamin B6
Which two transaminases are particularly useful in the clinic? Why?
Alanine transaminase and Aspartate transaminase.
Elevated levels are commonly seen in liver disease along with other pathologies
What are the two sources of nitrogen for use in urea biosynthesis?
Aspartate and ammonia
From what compound is aspartate and ammonia formed?
Glutamate
How is glutamate converted to aspartate for use in urea biosynthesis?
Glutamate + OAA –> alpha-ketoglutarate + asparate
How is glutamate converted to ammonia for use in urea biosynthesis?
Glutamate NAD(P)+ + H20 —> ammonia + alpha-ketoglutarate + NADPH
What is the chemical structure of urea?
H2N - C(=O) - NH2
What is the sequence of intermediates involved in the urea cycle?
NH3 + CO2–> Carbamoyl phosphate –> citrulline –> arginosuccinate –> arginine –> Urea + ornithine
What is the primary regulated enzyme of the urea cycle and its activator
Carbamoyl phosphate synthetase I
Allosteric activator: N-acetylglutamate
What is the name of the enzyme that produces urea from arginine?
Arginase
How would a high protein diet alter the rate of urea production?
High protein diet will increase the rate of urea production
Which two amino acids are the major carriers of nitrogen to the liver?
Alanine and glutamine are the main carriers of nitrogen to the liver.
They are found in higher concentrations in the blood
What is the purpose of urea biosynthesis?
Detoxification of ammonia
What are the consequences of decreased urea production?
Hyperammonenia predisposes to coma
Hepatic coma results from decreased capacity of the liver to remove ammonia via urea production; this can be due to acquired or genetic factors.
Differentiate glucogenic from ketogenic
Glucogenic: yields TCA cycle intermediates or pyruvate that can be used for gluconeogenesis
Ketogenic: yields acetyl CoA, acetoacetyl CoA or acetoacetate
How is the transient net synthesis and degradation of protein regulated in muscle?
After a meal: aa’s are transiently stored by stimulation of protein synthesis (through increased insulin)
Fasting: net protein degradation and release of aa’s for gluconeogenesis (by increased glucagon)
Indicate the function of the amino acids released during an overnight fast
During an overnight fast, the decrease in plasma amino acids and insulin leads to net protein degradation and release of amino acids for use by liver gluconeogenesis.
Describe the enzyme deficiency in classic (Type 1) phenylketonuria and the biochemical consequences of this deficiency.
Defect in phenylalanine hydroxylase (which converts phenylalanine to tyrosine). Requires the cofactor BH4.
This leads to build up of phenylalanine, which can then be shunted down side reactions such as phenylpyruvic acid.
Describe how symptoms of certain genetic diseases of amino acid catabolism can often be prevented by modification of diet.
You can avoid eating foods that contain certain amino acids.
