Proteins And Amino Acid Metabolism + PKU + Homocystinuria

Question 1

Outline phenylketonuria

Answer 1

Deficiency in phenylalanine hydroxylase

• Causes an accumulation of phenylalanine as it cant be converted to tyrosine
• Phenylalanine becomes transaminated to phenylpyruatve
• Accumulation of phenylketones

Question 2

Symptoms of PKU

Answer 2

Phenylketones in urine > musty smell
Severe intellectual disability
Developmental delay
Small head
Seizures
Hypopigmentation

Question 3

Outline homocystinuria

Answer 3

Cannot breakdown methionine to cysteine
Defect in cystathionine B-synthase
Build up of homocysteine > excreted in urine

Question 4

Treatment of homocystinuria

Answer 4

Low methionine diet
Less milk, meat, fish, cheese, eggs + nuts
Cysteine, vitamin B6, 12 and folate supplement

Question 5

Supplements can be used to treat homocystinuria
What supplement and why?

Answer 5

Vitamin V6, B12 + folate

Homocysteine > methionine is promoted by them
Less accumulation of homocysteine

Question 6

Treatment of PKU

Answer 6

Low phenylalanine diet
High tyrosine diet
Avoid artifical sweeteners
Avoid high protein foods - meat, milk + eggs

Question 7

Homocystinuria and Marfan’s;s syndrome have some similar clinal feature
What are they?
How can you distinguish between the two?

Answer 7

Similar:
- skeletal deformities
- lens dislocation

Different
- homocystine levels high in homocystinurea but normal in Marfan’s

Question 8

What is creatinine?

Answer 8

Breakdown product of creatine and creatine phosphate in muscles

Question 9

What does creatinine a useful clinical marker of?

Answer 9

• Real function
• Estimates muscle mass - Creatinine urine excretion over 24h is proportional to muscle mass

Question 10

What is an abnormal nitrogen balance?

Answer 10

negative N balance - Intake < output

Question 11

Causes of a negative nitrogen balance

Answer 11

Trauma
Infection
Malnutrition

Question 12

What are three major nitrogen containing compounds?

Answer 12

Amino acid
Proteins
Purine + pyrimidine

Question 13

What is nitrogen balance?

Answer 13

Nitrogen input - nitrogen output

Question 14

When is a positive nitrogen balance normal?

Answer 14

Growth
Pregnancy
Adult recovering from malnutrition

Question 15

What is protein turnover?

Answer 15

Balance between protein synthesis and protein degradation

Question 16

Example of a glucogenic amino acid

Answer 16

Alanine

Question 17

Example of a ketogenic amino acid

Answer 17

Leucine

Question 18

Example of both a glucogenic and ketogenic amino acid

Answer 18

Isoleucine

Question 19

When does mobilisation of protein reserves occur?

Answer 19

Extreme stress - starvation

Question 20

What are the 9 essential amino acids?

Answer 20

Isoleucine
Lysine
Threonine
Histidine
Leucine
Methionine
Phenylalanine
Tryptophan
Valine

If Learned This Huge List May Prove ** Truly Valuable

Question 21

What amino acids can be conditionally essential and when?

Answer 21

• Tyrosine - low in phenylalanine or phenylalanine hydroxylase deficient
  -Cysteine - low in methionine
• Arginine

Or in pregnancy and children

Question 22

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

Answer 22

Glycolysis intermediates
Pentose phosphate pathway
Kerbs cycle

Question 23

What are the pathways which facilitate removal of nitrogen from amino acids?

Answer 23

Transamination
Deamination

Question 24

Outline transamination

Answer 24

• Transfers amine group from one amino acid to another group e.g. keto acid
• require the coenzyme pyridoxal phosphate

Question 25

What are the aminotransferases in the liver function test?

Answer 25

Alanine aminotransferase ALT Aspartate aminotransferase AST

Question 26

What does alanine aminotransferase do?

Answer 26

Catalyses alanine + a-ketoglutarate > pyruvate + glutamate

Question 27

What does aspartate aminotransferase do?

Answer 27

Catalyses asparatate + a-ketoglutarate >oxaloacetate + glutamate

Question 28

Outline deamination

Answer 28

- Liberates amino acid group as free ammonia - in liver and kidneys - NH3 > NH4+ at physiological pH

Question 29

3 enzymes which deaminate amino acids

Answer 29

Amino acid oxidases Glutaminase Glutamate dehydrogenase

Question 30

How is urea excreted?

Answer 30

In urine via kidneys

Question 31

Management of urea cycle defects

Answer 31

Low protein diet Replace amino acids in diet with keto acids

Question 32

4 properties of urea

Answer 32

Non toxic Water soluble Chemically inert High nitrogen content

Question 33

Symptoms of urea cycle defects

Answer 33

Vomiting Lethargy Irritability Mental retardation Seizures Coma

Question 34

How many enzymes are involved in the urea cycle?

Answer 34

5

Question 35

Outline potential toxic effects of ammonia toxicity

Answer 35

- disruption of cerebral blood flow - ^pH - alters blood brain barrier - interference with TCA cycle - interference with aa transport and protein synthesis

Question 36

What are the two mechanisms to safely transport ammonia from tissues to liver?

Answer 36

**Glutamine** **Alanine**

Question 37

Outline the mechanism of glutamine in the safe transport of ammonia

Answer 37

- ammonia + glutamate > glutamine - glutamine transported in blood to liver or kidneys *glutaminase* - glutamine > ammonia + glutamate - liver: ammonia put into urea cycle - kidneys: excreted in urine

Question 38

Outline the mechanism of alanine in the safe transport of ammonia

Answer 38

- **transamination** - amine group transferred to glutamate - amine groups from glutamate > urea cycle - pyruvate is transaminated by glutamate > alanine - alanine is sent to liver - alanine > pyruvate - pyruvate > glycolysis

Question 39

What is the heel prick test used to test?

Answer 39

- sickle cell disease - cystic fibrosis - congential hypothyroidism - PKU - homocystinuria

Question 40

Cysteine vs cystine vs homocysteine vs homocystine

Answer 40

**Cysteine** - amino acid **Cystine** - 2 x cysteine **Homocysteine** - made from methionine **Homocystine** - 2 x homocysteine

Question 41

Outline the molecular basis of re feeding syndrome

Answer 41

- down regulations enzymes in urea cycle due to low protein intake - sudden high protein take overwhelms enzymes - ammonia toxicity occurs

Question 42

What is a main property of a glucogenic vs ketogenic amino acid?

Answer 42

- **glucogenic**: Can be converted to glucose truth gluconeogenesis - **ketogenic**: can be converted into acetyl coA