L2

Question 1

name three major nitrogen containing compounds we need to consider when thinking why nitrgoen metabolism is importnt

Answer 1

amino acids/proteins/nucleic acids/creatine phosphate

Question 2

what is creatinine?

Answer 2

the breakdown product of creatine and creatine phosphate in muscle

Question 3

creatinine is filtered by the kidneys and thus the creatinine in the urine over 24 hours gives us an estimation of what?

Answer 3

muscle mass (and renal function - levels in the urine are raised in renal damage)

Question 4

The average amount of nitrogen in our bodies at a given time is 2Kg,what is our primary source of nitrogen?

Answer 4

dietary protein

Question 5

Net loss of nitrogen is never normal but it is common, name some ways in which we lose some every day

Answer 5

trauma/infection/malnutrition

Question 6

What is nitrogen excreted as?

Answer 6

urea

Question 7

give an example of when we would have a positive and a negative nitrogen balance, this means our output doesn’t = our input

Answer 7

positive = pregnancy/growing 
negative = malnutrition

Question 8

amino acids can be used to synthesise proteins or as an energy source for metabolism. What is essential to ensure that toxic ammonia doesn’t build up as a result of this?

Answer 8

The removal of the amine group and digestion to urea

Question 9

What is the difference between ketogenic and glucogenic amino acids

Answer 9

Ketogenic amino acids are converted directly to acetyl CoA which is then used to generate ketone bodies

Glucogenic amino acids are converted into glucose

Question 10

give one example of a ketogenic amino acid and one example of a glucogenic one and one that is both

Answer 10

ketogenic - lysine/leucine
glucogenic - glutamate/alanine/cysteine/serine/aspartate/methionine/asparagine/valline/glycine/arginine/histidine
both - tyrosine/tryptophan/threonine/isoleucine/phenylaline

Question 11

what effects do the following have on protein synthesis?

a) insulin and growth hormone
b) glucocorticoids (e.g. cortisol)

Answer 11

a) increases (and decreases degradation)
b) decreases (and increases degradation - explains the purple striae in Cushing’s syndrome - the result of excess proteing degradation

Question 12

If your’e a vegetarina why is it important to eat a wide range of fruits and vegetables?

Answer 12

Because their proteins are generally considered lower quality as they are deficient in one or more essential amino acids thus more must be eaten to account for this

Question 13

What is meant by an ‘essential amino acid’ and what are they?

Answer 13

amino acids that cannot be synthesised by the body 
Isoleucine
Lysine
Threonine
Histidine
Leucine
Methionine
Phenylalanine
Tryptophan
Valine 

This list can be easily remembered by the mnemonic If Learned This List May Prove Truly Valuable

Question 14

What points in metabolism are the sources of carbon for synthesis of the non-essential amino acids

Answer 14

intermediates of glycolysis/pentose phosphate pathway/krebs cycle

Question 15

What are the two steps to the removal of nitrogen from amino acids called?

Answer 15

1) transamination

2) deamination

Question 16

Explain transamination

Answer 16

aminotransferase enzymes swap the amino group of one amino acid with the functional group of a keto acid (from krebs cycle) to make a new keto acid and either glutamate or aspartate. THE MAJORITY OF THE TIME IT IS GLUTAMATE WHICH IS MADE. This is because these two amino acids are more easily fed into the urea cycle

Question 17

What is essential for the creation of the aminotransferases used in transamination?

Answer 17

Vitamin B6

Question 18

The plasma levels of two particular aminotransferases are measured in liver function tests. What are these and what are their products?

Answer 18

Alanine aminotransferase (ALT) - converts alanine to glutamate
Asparate aminotransferase (AST) - converts glutamate to aspartate

Question 19

Diseases that are associated with particularly high levels of AST and ALT are those that cause extensive cellular necrosis in the liver. Give an example of one

Answer 19

Viral hepatitis/Autoimmune liver diseases/toxic injury

Question 20

What is deamination?

Answer 20

This is the liberation of the amino group as free amonnia, this occurs in the liver and kidney to prevent toxicity, the ammonia is then ultimately converted to urea and excreted as urine

Question 21

Apart from being a vehicle for excretion of ammonia what is another use of urea?

Answer 21

Has an osmotic role in the kidney tubules

Question 22

glutamate and aspartate both feed into the urea cycle to produce urea, what parts of the cell does the urea cycle take place in?

Answer 22

Cytoplasm and mitochondria of hepatocytes in the liver

Question 23

There are 5 enzymes involved in the urea cycle, what kind of diet would induce these enzyme levels and what kind of diet would repress them?

Answer 23

induce - high protein diet

repress - low protein diet/starvation

Question 24

Refeeding syndrome is a risk factor for severely malnourished patients who are recovering to a normal weight. What is refeeding syndrome and how must we avoid it?

Answer 24

After extended periods of malnourishment the enzymes of the urea cycle are repressed and thus suddenly eating a high protein diet can lead to accumulation of ammonia which is toxic and can cause death. To avoid you must slowly increase the nutritional content of the diet

Question 25

What accumulates as a result of genetic disorders causing partial loss of urea cycle enzyme function?

Answer 25

Ammonia and urea cycle intermediates

Question 26

Genetic defects in the urea cycle normally show one day after birth, some milder ones will show up in childhood. What are the symptoms and how would you manage this?

Answer 26

Symptoms - vomiting/mental retardation/seizures/coma/lethargy

Management - low protein diet/replacement of amino acids in diet with keto acids (because keto acids lack the amine group)

Question 27

How is ammonia safely transported from the tissues to the liver and kidneys to be made into urea for entry to the urea cycle?

Answer 27

IT is transported as glutamine and alanine to the targets where is then transaminated and deaminated back to ammonia

Question 28

There are a bunch of possible amino acid enzyme deficiencies but importantly we are interested in defects in phenylalanine metabolism. A defect in the enzyme which degrades it to tyrosine means we get an accumulation of phenylalanine all over the body. What are the signs and symptoms of this disease called phenylketonuria?

Answer 28

Symptoms - Musty smell of urine/ seizures/ microcephaly (small head)/ developmental delay/ hypopigmentation (lack of colour - v white in areas)

Signs - phenylketones in urine

Question 29

The symptoms of phyenylketonuria (PKU) mostly appear quire neurological, why is this?

Answer 29

Because phenylalanine isn’t being converted to tyrosin which is an important element of NA/Adrenaline/Dopamine/melanin and protein synthesis

Question 30

How would you treat a patient with phenylketonuria?

Answer 30

Low phenylalanine diet enhanced with tyrosine. Avoid high protein foods and artificial sweeteners

Question 31

Homocystinurias are excess homocysteine being exreted in the urine. This is because of a deficiency in a downstream enzyme. It shows similar symtpoms to PKU ,would be clinically distinguished by testing the urine for phenylketones or homocysteine. What is the treatment and why?

Answer 31

Low methionine diet (this is converted to homocysteine). Avoid high protein diet
Vitamin B6 supplementation

Question 32

All newborns are screened for PKU and other inborn errors of metabolism using the heel prick test (blood test from the heel), name another important disease it screens for

Answer 32

Sickle cell/CF/Congenital hypothyroidism