9. Protein and Amino Acid Metabolism

Question 1

What is creatinine the breakdown product of?

Answer 1

Creatine and Creatine phosphate in the muscle.

Question 2

How is creatinine link to muscle mass.

Answer 2

The amount excreted is proportional to muscle mass so provides an estimate of muscle mass.

Question 3

What can creatinine be used as a clinical marker for?

Answer 3

Muscle mass and kidney function.

Question 4

What contributes to intake of nitrogen?

Answer 4

Dietary protein.

Question 5

What contributes to the output of nitrogen?

Answer 5

Loss of skin, hair, nail and N-waste product in faeces and urine.

Question 6

Where is nitrogen stored in the body?

Answer 6

Amino acid pool and N-containing compounds.

Question 7

What is N equilibrium and what are the implications on body protein and health?

Answer 7

Where input= output. No change in body protein and normal healthy state in adults.

Question 8

What is positive N balance and what are the implications on body protein and health?

Answer 8

Intake > output. There’s an increase in body protein, there is normal health in growth and pregnancy or in adults recovering from malnutrition.

Question 9

What is negative N balance and what are the implications on body protein and health?

Answer 9

Intake

Question 10

What are the three routes an amino acid can go down to produce energy?

Answer 10

Glucogenic, ketogenic or both glucogenic and ketogenic.

Question 11

What is one example of a glucogenic amino acid?

Answer 11

Alanine, glycine, cysteine, serine, arginine, proline, histidine, glutamine, glutamate, methionine, valine, aspartate, asparagine.

Question 12

What is one example of a ketogenic amino acid?

Answer 12

Lysine or leucine.

Question 13

What is an example of a glucogenic/ketogenic amino acid?

Answer 13

Treonine, tryptophan, tyrosine, phenyalanine or isoleucine.

Question 14

When are protein reserves metabolised?

Answer 14

Under extreme stress, starvation.

Question 15

How is protein reserve metabolism regulated?

Answer 15

By hormonal control. Insulin and growth hormone decrease protein degradation but glucocorticoids increase protein degradation.

Question 16

What can excessive breakdown of protein occur in?

Answer 16

Cushing’s syndrome, can lead to striae formation.

Question 17

What are the nine essential amino acids?

Answer 17

Isoleucine
Leucine
Threonine
Histidine
Lysine
Methionine
Phenylalanine
Tryptophan
Valine

Question 18

Why is it essential that vegetarian diets have a wide variety of plant sources?

Answer 18

Because, unlike meat, proteins of plant origin are deficient in at least one essential amino acid so to obtain all essential amino acids, there must be a variety of plant proteins eaten.

Question 19

Where do carbon atoms for non-essential amino acid synthesis come from?

Answer 19

Intermediates of glycolysis, pentose phosphate pathway or Kreb’s cycle.

Question 20

What two main pathways facilitate removal of nitrogen from amino acids?

Answer 20

Transamination and deamination.

Question 21

What happens in transamination?

Answer 21

The R group from an amino acid and a keto acid swap over. Normally a-ketoglutarate is used to funnel the amino group to glutamate. But aspartate amino transferase uses oxaloacetate to funnel amino group to aspartate. The coenzyme pyridoxal phosphate is required.

Question 22

What are two key aminotransferase enzymes?

Answer 22

Alanine aminotransferase (converts alanine to glutamate) and aspartate aminotransferase (converts glutamate to aspartate).

Question 23

What happens in deamination?

Answer 23

The amino acid group is released as free ammonia, mainly happens in the liver and kidney.

Question 24

What happens to the ammonia produced in deamination?

Answer 24

It is converted to urea or excreted directly in urine.

Question 25

What enzymes can deaminate amino acids?

Answer 25

Amino acid oxidases, glutaminase and glutamate dehydrogenase.

Question 26

What are some factors of urea?

Answer 26

High nitrogen content, non-toxic, water soluble, chemically inert in humans, excreted in urine and has an osmotic role in kidney tubules.

Question 27

Where does the urea cycle take place?

Answer 27

In the liver.

Question 28

How is the urea cycle controlled?

Answer 28

By the amount of substrate available. High protein induces enzyme levels, low protein represses levels. The cycle is induced, not regulated.

Question 29

Why must refeeding be done gradually?

Answer 29

Because sudden high levels will lead to ammonia toxicity as the urea cycle won’t be up regulated quickly enough.

Question 30

What can defects in the urea cycle lead to?

Answer 30

Hyperammonaemia or accumulation/excretion of urea cycle intermediates.

Question 31

What does the severity of defects in the urea cycle depend on?

Answer 31

The nature of the defect and the amounts of protein consumed.

Question 32

How are defects in the urea cycle managed?

Answer 32

By a low protein diet and replacing amino acids with keto acids.

Question 33

What are some symptoms of defects in the urea cycle?

Answer 33

Vomiting, lethargy, irritability, mental retardation, seizures and coma.

Question 34

Why is ammonia toxicity a problem?

Answer 34

Ammonia is readily diffusible across the blood brain barrier. It can lead to potentially toxic side effects, such as: interference with amino acid transport and protein synthesis, disruption of cerebral blood flow, pH becomes more alkaline, metabolism of excitatory amino acid neurotransmitters is interfered with, alternation of the blood-brain barrier and interference of the TCA cycle.

Question 35

Briefly explain the two mechanisms for safe transport of ammonia from the tissues for disposal.

Answer 35

1) Glutamine. Ammonia combines with glutamate to from glutamine, Glutamine is transported to the liver or kidneys and us cleaved glutaminase to reform glutamate and ammonia, the ammonia is fed into the urea cycle in the liver or excreted directly in urine from the kidneys.
2) Alanine. alanine is formed by transamination of pyruvate million it’s transported in the blood to the liver and is converted back to pyruvate by transamination, the amino group is fed into the urea cycle for disposal as urea and pyruvate is used to synthesise glucose to be fed back into tissues.

Question 36

How are amino acid metabolism problems screened for?

Answer 36

Using the heel prick test.

Question 37

How are defects of amino acid metabolism managed?

Answer 37

By restricting the specific amino acids in diet.

Question 38

Explain the most common inborn error amino acid metabolism.

Answer 38

Phenylketonuria (PKU). It’s caused by a deficiency in phenylalanine hydroxylase. It’s an autosomal recessive genetic abnormality. It causes accumulation of phenylalanine in the tissue, plasma and urine.

Question 39

How is phenylketonuria treated?

Answer 39

Having a low phenylalanine diet, avoid artificial sweeteners, avoid high protein foods.

Question 40

What are the symptoms of phenylketonuria?

Answer 40

Intellectual disability, developmental delay, microcephaly (small head), seizures and hypopigmentation.

Question 41

What is homocystinurias?

Answer 41

Problems metabolising methionine, leading to excess homocysteine excreted in urine, it’s an autosomal recessive disorder commonly caused by a defect in cystathionine B-synthase.

Question 42

How are homocystinurias treated?

Answer 42

Low methionine diet, avoid milk, meat, fish, cheese, eggs, and use cysteine, vitamin B6, betting, B12 and folate supplements.

Question 43

What are some major nitrogen containing compounds?

Answer 43

Amino acids, proteins, purine and pyrimidines.