Amino Acid Metabolism

Question 1

What are the sources of free amino acids in the body?

Answer 1

Degradation of: ingested protein, biosynthesis of some (non-essential), and degradation of endogenous protein

Question 2

Differentiate essential from non-essential amino acids

Answer 2

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

Question 3

What are free amino acids used for?

Answer 3

Resynthesis of endogenous protein
Precursors for the synthesis of other biomolecules
Energy production (and amino group is excreted as urea in the process)

Question 4

Is the biosynthesis of amino acids sufficient to allow net synthesis of protein?

Answer 4

No. If you don’t eat enough protein in your diet, you will eventually lose muscle mass

Question 5

What are two pathways by which protein degradation occurs?

Answer 5

Lysosome and proteosome

Question 6

What is the half life of a protein?

Answer 6

The range varies from minutes to days

Question 7

What is the “turnover” of protein in an adult?

Answer 7

Adults degrade and resynthesize 2-3% (~300g) of their total body protein every day.

Question 8

What happens to excess amino acids?

Answer 8

Excess amino acids are degraded, not stored.

Question 9

What is the recommended dietary allowance for daily protein?

Answer 9

55g

Question 10

55g of amino acids are degraded daily. What are they being used for?

Answer 10

Biosynthesis of purines, pyrimidines and porphyrins

Carbon skeletons: (used for energy)

Question 11

What would happen if you ate a protein free diet?

Answer 11

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

Question 12

Define nitrogen balance

Answer 12

Nitrogen ingested (protein) = nitrogen excreted (urea)

If you eat more protein, you pee out more urea

Question 13

The degradation of amino involves what two processes? What is their role?

Answer 13

1) Removal of the nitrogen to form urea –> excretion for nitrogen balance
2) Degradation of the carbon skeletons –> energy production

Question 14

What is the first step in the degradation of many amino acids?

Answer 14

transamination

Question 15

Where does biosynthesis urea occur?

Answer 15

The liver

Question 16

Describe transamination.

Answer 16

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

Question 17

What cofactor is required for transaminases?

Answer 17

Pyridoxal phosphate- a derivative of vitamin B6

Question 18

Which two transaminases are particularly useful in the clinic? Why?

Answer 18

Alanine transaminase and Aspartate transaminase.

Elevated levels are commonly seen in liver disease along with other pathologies

Question 19

What are the two sources of nitrogen for use in urea biosynthesis?

Answer 19

Aspartate and ammonia

Question 20

From what compound is aspartate and ammonia formed?

Answer 20

Glutamate

Question 21

How is glutamate converted to aspartate for use in urea biosynthesis?

Answer 21

Glutamate + OAA –> alpha-ketoglutarate + asparate

Question 22

How is glutamate converted to ammonia for use in urea biosynthesis?

Answer 22

Glutamate NAD(P)+ + H20 —> ammonia + alpha-ketoglutarate + NADPH

Question 23

What is the chemical structure of urea?

Answer 23

H2N - C(=O) - NH2

Question 24

What is the sequence of intermediates involved in the urea cycle?

Answer 24

NH3 + CO2–> Carbamoyl phosphate –> citrulline –> arginosuccinate –> arginine –> Urea + ornithine

Question 25

What is the primary regulated enzyme of the urea cycle and its activator

Answer 25

Carbamoyl phosphate synthetase I

Allosteric activator: N-acetylglutamate

Question 26

What is the name of the enzyme that produces urea from arginine?

Answer 26

Arginase

Question 27

How would a high protein diet alter the rate of urea production?

Answer 27

High protein diet will increase the rate of urea production

Question 28

Which two amino acids are the major carriers of nitrogen to the liver?

Answer 28

Alanine and glutamine are the main carriers of nitrogen to the liver.

They are found in higher concentrations in the blood

Question 29

What is the purpose of urea biosynthesis?

Answer 29

Detoxification of ammonia

Question 30

What are the consequences of decreased urea production?

Answer 30

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.

Question 31

Differentiate glucogenic from ketogenic

Answer 31

Glucogenic: yields TCA cycle intermediates or pyruvate that can be used for gluconeogenesis

Ketogenic: yields acetyl CoA, acetoacetyl CoA or acetoacetate

Question 32

How is the transient net synthesis and degradation of protein regulated in muscle?

Answer 32

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)

Question 33

Indicate the function of the amino acids released during an overnight fast

Answer 33

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.

Question 34

Describe the enzyme deficiency in classic (Type 1) phenylketonuria and the biochemical consequences of this deficiency.

Answer 34

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.

Question 35

Describe how symptoms of certain genetic diseases of amino acid catabolism can often be prevented by modification of diet.

Answer 35

You can avoid eating foods that contain certain amino acids.