2 - Protein and Amino Acid Metabolism

Question 1

What are the major nitrogen containing compounds?

Answer 1

• Amino acids
• Proteins
• Purines and pyrimidines (DNA/RNA)
• Small amounts in others (e.g. haem, creatine phosphate, neurotransmitters, hormones)

Question 2

What is creatinine and how is it used clinically?

Answer 2

A breakdown product of creatine and creatine phosphate. Usually produced at a constant rate and filtered into the urine.

Used as a clinical marker to estimate muscle mass (measure creatinine excretion over 24 hrs). Also used as an indicator of renal function.

Question 3

• How is nitrogen brought into the body?
• Where is nitrogen stored within the body?
• Where is nitrogen excreted from the body?

Answer 3

• Nitrogen intake comes from dietary protein
• Nitrogen is stored in body protein, the amino acid pool and other nitrogen-containing compounds
• Nitrogen is excreted through waste products in faeces and urine and through loss of skin, hair and nails

Question 4

Normal nitrogen balance is when N intake = N output. What causes positive or negative N balance?

Answer 4

• Positive - Intake > Output - increase in body protein. Normal state in growth, pregnancy or when recovering from malnutrition
• Negative - Intake < Output - loss of body protein. Never normal - commonly trauma, infection or malnutrition

Question 5

Describe the process of protein breakdown in the body.

Answer 5

• Dietary protein is digested into free amino acids
• The amino group is converted to urea and excreted in the urine
• The carbon skeleton is broken down into glucose and ketone bodies

Question 6

Give one example of:

• A glucogenic amino acid
• A ketogenic amino acid
• An amino acid that’s both glucogenic and ketogenic

Answer 6

• Glucogenic - Alanine
• Ketogenic - Lysine
• Glucogenic and ketogenic - Tryptophan

Question 7

Decribe the hormonal control of protein synthesis and degradation.

Answer 7

• Insulin and growth hormone increase protein synthesis and decrease protein degradation
• Glucocorticoids (e.g. cortisol) decrease protein synthesis and increase protein degradation

Question 8

What is the effect on protein reserves of Cushing’s syndrome?

Answer 8

Excess cortisol causes excessive protein breakdown. This weakens the skin structure leading to striae (stretch marks).

Question 9

What are the three groups of an amino acid?

Answer 9

Amino group

Carboxyl group

R group

Question 10

Give an example of an essential amino acid.

Answer 10

Isoleucine

Question 11

In children and pregnant women there are three further essential amino acids. What are they and why are they necessary?

Answer 11

Arginine, tyrosine and cysteine

Required due to the high rate of protein synthesis

Question 12

When non-essential amino acids are synthesised by the body where do the following come from?

• carbon atoms
• amino groups

Answer 12

• Carbon atoms - intermediates of glycolysis, pentose phosphate pathway, krebs cycle
• Amino groups - provided by other amino acids by transamination or from ammonia

Question 13

Give some examples of some non-protein nitrogen-containing compounds.

Answer 13

• Catecholamines
• Glutathione
• Serotonin
• Histamine
• GABA
• Purines
• Haem

Question 14

What two pathways remove nitrogen from amino acids?

Answer 14

Transamination

Deamination

Question 15

What are the two key aminotransferases involved in transamination and how do they differ?

Answer 15

Alanine aminotransferase (ALT)

Converts alanine to glutamate (and alpha-ketoglutarate to keto acid)

Aspartate aminotransferase (AST)

Converts glutamate to aspartate (and oxaloacetate to keto acid)

Question 16

A derivative of which vitamin is required for all aminotransferases?

Answer 16

Vitamin B6

Question 17

Plasma ALT and AST are measured as part of …….. ………… …………

Levels are particularly high in what conditions?

Answer 17

Liver function tests

• Viral hepatitis
• Autoimmune liver diseases
• Toxic injury (e.g. death cap muschrooms)

Question 18

What is deamination? Give an example of an enzyme that performs this process.

Answer 18

• Amino group is converted into free ammonia (toxic so converted to urea) in the liver and kidney. Remaining keto acids can be used for energy
• Performed by: amino acid oxidases, glutaminase, glutamate dehydrogenase

Question 19

Describe the basic concepts of the urea cycle.

Answer 19

• Occurs in the liver and uses 5 enzymes
• Regulated based on demand for disposal of ammonia
  
  • High protein diet induces enzyme levels
  • Low protein diet or starvation represses levels

Question 20

What is refeeding syndrome and when might this occur? How is this avoided?

Answer 20

• Ammonia toxicity when nutritional support is given to severely malnourished patients, as the urea cycle has been downregulated
• Risk if BMI < 16, unintentional weight loss of >15% in 3-6 months or 10+ days with little nutritional intake
• Refeed gradually at 5-10 kcal/kg/day

Question 21

There are some autosomal recessive disorders caused by defects in enzymes of the urea cycle. What can these lead to?

Answer 21

• Hyperammonaemia
• Accumulation/excretion of urea cycle intermediates

Question 22

How might ammonia toxicity present clinically and how is it managed?

Answer 22

• Vomiting, lethargy, irritability, mental retardation, seizures, coma
• Severe disorders show symptoms within one day of birth. Mild disorders may not present until early childhood
• Managed with low protein diet and replacing amino acids in the diet with keto acids

Question 23

Describe some of the toxic effects of ammonia.

Answer 23

• Readily diffusible and highly toxic
  
  • Interferes with amino acid transport and protein synthesis
  • Disrupts cerebral blood flow
  • Alkaline - pH effects
  • Interferes with excitatory amino acid neurotransmitters (e.g. glutamate)
  • Interferes with the TCA cycle

Question 24

By what two ways is nitrogen in amino acids safely transported to the liver?

Answer 24

• Glutamine
  
  • Ammonia combined with glutamate, cleaved back in the liver by glutaminase and ammonia is fed into the urea cycle
• Alanine
  
  • Amine groups transferred to glutamate by transamination. Pyruvate is then transaminated by glutamate to form alanine
  • Reversed in the liver and pyruvate used to make glucose

Question 25

Give some examples of conditions tested for in the heel prick test in newborns.

Answer 25

• Sickle cell disease
• Cystic fibrosis
• Congenital hypothyroidism
• Phenylketonuria (PKU)
• Homocystinuria

+ other inborn errors of metabolism

Question 26

What is phenylketonuria (PKU) and how is it treated?

Answer 26

• Autosomal recessive deficiency in phenylalanine hydroxylase, leads to accumulation of phenylalanine and formation of phenylketones in urine
• Treated with low phenylalanine diet, avoiding artificial sweeteners and avoiding high protein foods. Diet is enriched with tyrosine as it cannot be made from phenylalanine

Question 27

What are the symptoms of phenylketonuria?

Answer 27

• Severe intellectual disability
• Developmental delay
• Microcephaly
• Seizures
• Hypopigmentation

Question 28

What is homocystinuria?

Answer 28

• Problem breaking down methionine leads to excess homocystine (oxidised homocysteine)
• Defect in cystathionine B-synthase is most common
• Affects connective tissue, muscle, CNS and CVS

Question 29

How is homocystinuria treated?

Answer 29

• Low methionine diet
  
  • Avoid milk, meat, fish, cheese, eggs and nuts
• Cysteine, Betaine, Vitamins B6 & B12 and folate supplements