S1 Protein and Amino Acid Metabolism

Question 1

What are the two key concepts of nitrogen metabolism?

Answer 1

1. Nitrogen balance

2. Protein turnover

Question 2

What is creatinine?

Answer 2

• breakdown product of creatine and creatine phosphate in muscle
• a clinical marker for muscle mass and renal function

Question 3

How is creatinine a clinical marker for muscle mass and renal function?

Answer 3

1. Muscle mass - produced at a constant rate depending on muscle mass
2. Renal function - filtered via kidneys into urine, if a lower level than norm present in urine, sign of renal damage

Question 4

What are the three types of nitrogen balance?

Answer 4

1. N equilibrium (intake = output) - the norm
2. Positive N balance (intake > output) - norm in growth and pregnancy or malnutrition recovery
3. Negative N balance (intake < output) - never the norm, caused by trauma, infection or malnutrition

Question 5

What is protein turnover?

Answer 5

• Breakdown of older proteins, replaced by new proteins.
• Free amino acids from digestion, new (de novo) amino acid synthesis, proteolysis
• Free amino acids used to synthesis cellular proteins, processed by the liver (broken down to carbon skeleton - used for energy ad amino group - excreted)

Question 6

After the liver has processed free amino acids, what is the carbon skeleton used for?

Answer 6

Dependent on the amino acid (it’s side chain) the carbon skeleton becomes a glucogenic amino acid (gluconeogenesis) or a ketogenic amino acid (ketone bodies). Both of which produce energy

Question 7

What happens to the amino group of an amino acid after liver metabolism?

Answer 7

Amino group —> urea —> urine

• amino group can form ammonia (toxic) so mechanisms are in place to remove ammonia - converted to urea in mammals

Question 8

Give 3 examples of glucogenic amino acids.

Answer 8

1. Alanine
2. Glycine
3. Aspartate

Question 9

Give 3 examples of ketogenic amino acids.

Answer 9

1. Lysine
2. Leucine
3. Tyrosine (also glucogenic)

Question 10

When are protein reserves used as fuel/energy? How is it mobilised?

Answer 10

During extreme stress e.g. starvation

Mobilised by hormone control

Question 11

Which hormones increase/decrease protein synthesis and protein degradation?

Answer 11

Protein synthesis - increased by insulin and growth hormone, decreased by glucocorticoids

Protein degradation - increased by glucocorticoids, decreased by insulin and growth hormone

Question 12

What is an example of a glucocorticoids?

Answer 12

Cortisol

Question 13

What is Cushing’s syndrome?

Answer 13

Excessive breakdown of protein due to excess cortisol - weakens the skin structure leading to striae formation

Question 14

What are the 9 essential amino acids?

Answer 14

1. Isoleucine
2. Lysine
3. Threonine
4. Histidine
5. Leucine
6. Methionine
7. Phenylalanine
8. Tryptophan
9. Valine

Question 15

What 3 amino acids become essential in kids and pregnant women? And why?

Answer 15

1. Arginine
2. Tyrosine
3. Cysteine

Because they have a higher rate of protein synthesis

Question 16

Are proteins from animal origin or plant origin higher quality?

Answer 16

Animal origin - contain all essential amino acids (plant origin are usually deficient in one or more essential amino acid)

Question 17

In what 3 pathways can non-essential amino acids be synthesised?

Answer 17

1. Intermediates of glycolysis
2. Pentose phosphate pathway
3. Krebs cycle

Question 18

Some amino acids are required for synthesis of important compounds, what can tyrosine, cysteine, tryptophan, histidine, glutamate, glycine, arginine and serine be used to synthesise?

Answer 18

1. Tyrosine - thyroid hormones, melanin, catecholamines
2. Cysteine - glutathione (GSH/GSSG)
3. Tryptophan - serotonin (5HT), melatonin
4. Histidine - histamine
5. Glutamate - GABA
6. Glycine - glutathione, creatine, haem
7. Arginine - nitric oxide (NO)
8. Serine - sphingosine

Question 19

How is nitrogen removed from amino acids (2 ways)?

Answer 19

1. Transamination

2. Deamination

Question 20

Why do you remove the amino group from an amino acid?

Answer 20

Allows the carbon skeleton to be utilised in oxidative metabolism

Question 21

What is transamination?

Answer 21

A chemical reaction that transfers an amino group to a ketoacid (from a amino acid) to form new amino acids

E.g. use of alpha-ketoglutarate (ketoacid) to transfer the amino group

Question 22

What are the two aminotransferase enzymes?

Answer 22

1. Alanine aminotransferase (ALT) - converts alanine to glutamate
2. Aspartate aminotransferase (AST) - converts glutamate to aspartate

Question 23

What organ function test are plasma levels of ALT and AST measured?

Answer 23

Liver function test - levels higher in conditions that cause cellular necrosis e.g. viral hepatitis, autoimmune liver diseases and toxic injury

Question 24

What is deamination?

Answer 24

Amino group lost from amino acid (forming a ketoacid) and forms ammonia.

Ketoacids can be utilised for energy.

The ammonia is toxic so is converted to urea and excreted in urine.

Question 25

Where does deamination occur?

Answer 25

Liver and kidney

Question 26

What 3 enzymes deaminate amino acids?

Answer 26

1. Amino acid oxidases 2. Glutaminase 3. Glutamate dehydrogenase

Question 27

What is ammonia converted into at physiological pH?

Answer 27

Ammonium ions (NH4+)

Question 28

What is urea? What is it like?

Answer 28

* has a high nitrogen content * non-toxic * water soluble * chemically inert in humans * excreted in urine via kidneys * osmotic role in kidney tubules

Question 29

What is the urea cycle?

Answer 29

Occurs in the liver and involved 5 enzymes (the cycle is regulated on demand, it depends on the level of protein metabolism (related to need to dispose of ammonia))

Question 30

What is refeeding syndrome?

Answer 30

When lots of highly nutritional/high protein content food is given to severely malnourished patients - leads to a sudden shift in electrolytes that help your body metabolise food.

Question 31

What defects can occur in the urea cycle?

Answer 31

* autosomal recessive genetic disorders caused by deficiency of an enzyme in the urea cycle * mutations causing partial loss of enzyme function 1. Hyperammonaemia (excess ammonia in the blood) 2. Accumulation/excretion of urea cycle intermediates

Question 32

How do you manage defects in the urea cycle?

Answer 32

Have a low protein diet and replace amino acids in your diet with ketoacids (less amino groups needing to be fed into urea cycle)

Question 33

What are symptoms of defects in urea cycle?

Answer 33

Vomiting, lethargy, irritability, seizures, coma and mental retardation (VLISCR RISCLIV)

Question 34

How is ammonia toxic to the body?

Answer 34

1. Interferes with amino acid transport and protein synthesis 2. Makes pH more alkaline 3. Alteration of blood-brain barrier 4. Interference with TCA cycle (reacts with alpha-ketoglutarate forming glutamate)

Question 35

What two mechanisms are used for the safe transport of amino acid nitrogen from tissues to the liver for disposal?

Answer 35

1. Glutamine - ammonia + glutamate = glutamine, transported in the blood, cleaved by glutaminase, ammonia fed into urea cycle from liver to kidneys. Glutamine has two amino groups so an efficient transporter. 2. Alanine - glutamate gains amino group by transamination, then Pyruvate transaminated by glutamate to form alanine, transported in blood, converted back to pyruvate in the liver (transamination), amino group fed into urea cycle via glutamate.

Question 36

What is phenylketonuria (PKU)?

Answer 36

Caused by deficiency in phenylalanine hydroxylase (autosomal recessive). Leads to an accumulation of phenylalanine in tissues, plasma and urine - have phenylketones in urine (test this) and urine has a musty smell. Have a diet high in tyrosine (tyrosine usually produced from phenylalanine) and low in phenylalanine

Question 37

Can most among acid metabolism diseases be avoided with early intervention?

Answer 37

Yes - babies have the heel prick test to test for these metabolism errors

Question 38

What is a main symptom of amino acid metabolism diseases?

Answer 38

Intellectual impairment

Question 39

What is homocystinuria?

Answer 39

Problems with breaking down methionine leads to excess homocysteine (autosomal recessive) - defect in cystathionine beta-synthase. Treat with a low methionine diet, supplement cysteine into diet as it’s not made

Question 40

Elevated plasma levels of homocysteine can be associated with what type of disease?

Answer 40

Cardiovascular disease