MEH - Protein and amino acid metabolism

Question 1

Name 4 important nitrogen containing compounds in the body

Answer 1

Proteins
Amino acids
RNA/DNA
Creatine

Question 2

What is creatinine and what is it used for clinically (2)?

Answer 2

Breakdown of creatine and phosphocreatine in muscle.

Usually excreted at a constant rate - is proportional to muscle mass so can be used to estimate muscle mass

Also indicator of renal function (raised level on damage to nephrons)

Question 3

What are the normal figures for nitrogen balance in 70Kg man? What is the amino acid pool in the body?

Answer 3

16g in via diet
2g out via hair skin nails
14g out via urine and faeces

16g amino acid pool

Question 4

Is a negative nitrogen balance normal? What are some causes?

Answer 4

Never normal

Causes e.g. infection, malnutrition, trauma

Question 5

What part of protein metabolism is a potential source of ammonia?

Answer 5

Removal of the amino group - ammonia quickly converted to urea which isn’t toxic

Ammonium ions are also toxic

Question 6

Name a glucogenic, ketogenic amino acid and one that does both

Answer 6

1) Glucogenic - Alanine
2) Ketogenic - Lycine
3) Both - Tryptophan

Question 7

When does AA mobilisation occur? How is it regulated?

Answer 7

During extreme starvation

Under hormonal control:

Insulin/growth hormone - decrease mobilisation and increase protein synthesis

Cortisol - increase mobilisation and decrease protein synthesis

Question 8

How can Cushing’s syndrome lead to striae?

Answer 8

Excess cortisol
Excess protein breakdown
Weakens skin structure - striae

Question 9

What are the 9 essential AAs?
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Learnt
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Answer 9

Isoleucine
Lysine
Threonine
Histidine
Leucine
Methionine
Phenylalanine
Tryptophan
Valine

Question 10

Which amino acids are conditionally essential and what does this mean?

Answer 10

Arginine
Tyrosine
Cysteine

In pregnancy/children these may become essential so will need to be supplemented from the diet

Question 11

Non-essential amino acids can be synthesised - Where does the carbon skeleton come from for this (3)? Where does the amino group come from (2)?

Answer 11

Can come from:

Glycolysis intermediates (C3)
Pentose phosphate pathway (C4 & C5)
Krebs Cycle (C4 & C5)

Amino group comes from transamination from another amino acid - or from ammonia.

Question 12

What is hydrogen sulphide and what is the relevance of amino acids in relation to it?

Answer 12

It is a signalling molecule that requires specific amino acids in it’s synthesis

Question 13

What other types of compounds require amino acids for their synthesis?

Answer 13

• Some neurotransmitters - GABA, 5-HT
• Hormones - e.g. thyroid
• Signalling molecules - NO

Question 14

What part of the amino acid is used in oxidative metabolism and how?

Answer 14

The carbon skeleton

• Removal of amino group
• Carbon skeleton will then go onto make ketones or glucose to then go onto stage 3 and 4 metabolism (TCA cycle and ETC)

Question 15

What is the most common amino acid formed from transamination? From what intermediate (ketoacid).

Answer 15

Glutamate from alpha-ketoglutarate

Question 16

Which amino acid is the exception and what does it form/via which intermediate (ketoacid)?

Answer 16

Aspartate aminotransferase used oxaloacetate and forms aspartate

Question 17

What is pyridoxal phosphate? From which B vitamin is it derived?

Answer 17

It is a coenzyme that is required for all aminotransferases. It is a derivative of vitamin B6.

Question 18

What are ALT and AST and their roles?

Answer 18

Alanine Aminotransferase - converts alanine to glutamate

Aspartate aminotransferase - converts glutamate to aspartate.

Question 19

When are ALT and AST used clinically and what do they indicate?

Answer 19

Used to show liver damage - levels are particularly high in liver necrosis e.g. viral hepatitis, autoimmune liver diseases, toxic injury (e.g. alcohol).

Question 20

In deamination - what needs to occur immediately after and why? What does a deaminised amino acid become?

Answer 20

Urea cycle - to prevent toxic effects of ammonia

A ketoacid

Question 21

Which three enzymes deaminate amino acids from the lecture?

Answer 21

Amino acid oxidases
Glutaminases
Glutamate dehydrogenase

Question 22

What other role does urea play apart from ammonia?

Answer 22

Osmotic role in kidney tubules

Question 23

Where does the urea cycle occur? How many enzymes?

Answer 23

In the liver - 5 enzymes

Question 24

What happens in refeeding syndrome? What are the risk factors?

Answer 24

Urea cycle is down regulated so increasing protein intake rapidly will lead to ammonia toxicity. Risk factors are BMI <16, Unintentional weight loss >15% in 3-6months, 10days or more with little or no nutritional intake

Question 25

What can happen with a defect in urea cycle enzymes? What symptoms? How do you manage these disorders?

Answer 25

Autosomal recessive disorders caused by deficiency in one or more enzymes of urea cycle. Can get hyperammonaemia, accumulation of urea cycle intermediates. - Vomitting - Lethargy - Irritability - Mental retardation - Seizures - Coma - Death Low protein diet, replace amino acids in diet with ketoacids

Question 26

Why is ammonia so toxic?

Answer 26

Readily diffusible and toxic to brain - Interferes with amino acid transport and protein synthesis - Disruption of cerebral blood flow - pH effects - alkalising - Interferes with TCA cycle - Interferes with metabolism of excitatory amino acid neurotransmitters - Interferes with BBB

Question 27

How is ammonia removed from tissues before being removed by the urea cycle or immediately excreted by kidney (2)? Which enzyme?

Answer 27

1) Glutamine - ammonia combines with glutamate to form glutamine - travels in blood to liver - reforms glutamate and ammonia by glutaminase - enters urea cycle 2) Alanine - ammonia combines with pyruvate to form alanine - transported to liver by blood where it is converted back to alanine by transamination - Amino group then fed into urea cycle for disposal, pyruvate can be used to synthesise glucose which can be fed back to tissues.

Question 28

There are over 50 inherited diseases of involving defects in amino acid metabolism - what is the most common area of defect?

Answer 28

Enzymes - partial or total loss of function

Question 29

What is PKU and what happens? What chromosome? Why is the urine musty? What is the treatment?

Answer 29

Phenylketonuria - deficiency in phenylalanine hydroxylase so can't convert phenylalanine into tyrosine to make DA, NA, Adrenaline, Melanin, Thyroid hormone, protein synthesis. Chromosome 12 Symptoms are developmental delay, severe intellectual disability, microcephaly, seizures, hypopigmentation Accumulation of phenylketones in urine - musty smell Treatment - low phenylalanine diet - avoid artificial sweeteners avoid high protein food like meat, milk, eggs

Question 30

What are homocystinurias? Which enzyme defect? What is the treatment? What is elevated plasma homocysteine associated with?

Answer 30

Problem in the breakdown of methionine - defect in cystathionine beta-synthase. Symptoms are connective tissue problems, muscles, CNS, CVS. Treatment is low methionine diet avoid milk fish meat cheese eggs, nuts, peanut butter. Supplement with cysteine, Vit B6, B12, betaine and folate. Elevated homocysteine in plasma is associated with CVD

Question 31

Where does transamination vs deamination occur in the body?

Answer 31

Transamination - widespread but mostly liver, skeletal muscle, cardiac muscle and kidney. Mainly liver? Deamination - mainly liver and kidney

Question 32

What can increase the amount of urea cycle enzymes?

Answer 32

Amount of ammonia needing to be disposed of | High protein diet

Question 33

Is the urea cycle regulated?

Answer 33

No but it is inducible (by two things above) and suppressed by low protein diet

Question 34

What two ways can ammonia be detoxified in the body?

Answer 34

Either via urea cycle in the liver | Or being used in the synthesis of N compounds e.g. glutamine (Ammonia+Glutatmate)

Question 35

Why is glutamine at higher concentration than other amino acids in the body?

Answer 35

As it is converted from Ammonium + Glutamate to glutamine to be excreted

Question 36

What is the difference between the liver and kidney in how they deal with ammonia?

Answer 36

Liver - urea cycle detoxifies ammonia by converting it to urea Kidney - ammonia directly excreted into urine

Question 37

What is thought to be one of the main features of ammonia toxicity?

Answer 37

The fact it combines with alpha-ketoglutarate to form glutamate and this removes alpha-ketoglutarate from the TCA cycle leading to less energy being made in CNS cells