2 - Proteins and Amino Acid Metabolism

Question 1

What compounds contain nitrogen?

Answer 1

• Amino acids
• Proteins
• CK
• Neurotransmitters
• Haem

Question 2

What can Creatinine be a measure of?

Answer 2

• Proportional to muscle mass at a constant rate
• Indicator of renal function (raised level when damage)

Question 3

What is nitrogen balance?

Answer 3

Question 4

What is protein turnover?

Answer 4

Question 5

What are some examples of glucogenic and ketogenic amino acids?

Answer 5

G: Arginine, Proline, Valine

K: Lysine and Leucine

Both: Threonine, Tryptophan

Question 6

When are protein reserves mobilised?

Answer 6

Prolonged starvation by hormones

Question 7

What is this caused by?

Answer 7

• Cushing’s Syndrome
• Excess cortisol (due to steroid drugs) so weaking skin structure leading to striae

Question 8

Apart from diet how can amino acids be synthesised?

Answer 8

1.

Question 9

Apart from proteins, what other important compounds are amino acids required for?

Answer 9

Question 10

How and why is nitrogen removed from amino acids?

Answer 10

• Removed so the amino acids can be used in oxidative metabolism

- Transanimation or Deanimation

Question 11

What is transanimation?

Answer 11

• Converting an amine group from an amino acid to a keto acid to form a new amino acid that can be excreted
• Most aminotransferase enzymes use a-ketoglutarate to form glutamate

- Apart from aspartate aminotransferase which uses oxaloacetate to form aspartate

Question 12

What do aminotransferases need to function?

Answer 12

Coenzyme pyridoxal phosphate made from Vitamin B6

Question 13

What are markers for the liver function test?

Answer 13

ALT - Alanine to Glutamate

AST - Aspartate to Glutamate

High - Viral hepatitis, autoimmune liver disease, toxic injury (death-cap mushrooms)

Question 14

What is deanimation?

Answer 14

• Removing amino acid as free ammonia, mainly in the liver and kidney
• The keto acid produced can be used for energy
• Important for D-amino acids from plants and microorganisms

Question 15

What happens to ammonia after deanimation?

Answer 15

Very toxic so enters the urea cycle and is excreted into the urine. Converted back to ammonia by bacteria once weed out

Question 16

What are the features of urea?

Answer 16

• High nitrogen content
• Water soluble
• Inert
• Osmotic role in kidneys

Question 17

What is the urea cycle?

Answer 17

• 5 Enymes involved
• Inducible not regulated
• High protein diet induces enzyme and low protein diet represses

Question 18

What are risk factors for refeeding syndrome?

Answer 18

Question 19

What can happen with defects in the urea cycle and how can you manage the symptoms?

Answer 19

• Autosomal recessive
• Partial loss of enzymes
• Leads to hyperammonaemia and accumulation of urea cycle intermediates
• Severely can have onset a day after birth and can die. Mild may show in childhood

Question 20

What are the theories of ammonia toxicity?

Answer 20

Toxic to brain. Need 25-40 ummol/L

• pH effects (alkaline)
• Disruption of cerebral blood flow
• Interference with amino acid transport and protein synthesis
• Interference with TCA cycle (reacting with a-ketoglutarate to from glutamate)
• Interfering with BBB

Question 21

How is nitrogen safely transported from tissues to the liver

Answer 21

See lecture 2 for explanation. REALLY IMPORTANT TO LEARN

Question 22

What is the heel prick test?

Answer 22

• If left untreated, can lead to intellectual impairment but if detected can limit amino acids
• Due to loss of enzyme activity

Question 23

What is phenylketonuria (PKU)?

Answer 23

• Most common inborn error in phenylalanine hydroxylase deficiency
• Build up of phenylketones in urine, build up of phenylalanine in tissues, lack of tyrosine
• Autosomal recessive

Question 24

What is homocystinurias?

Answer 24

• Autosomal recessive issue with breaking down methionine
• Defect in cystathione b-synthase
• Excess of homocystine excreted in urine
• Need cysteine, vit b, folate supplements

Question 25

What is gout?

Answer 25

Defective purine metabolism leading to increased production or uric acid. Form monosodium urate crystals which neutrophils try to phagocytose but they are killed themselves. Leads to local pain and inflammation

Question 26

What are the indirect effects of alcohol consumption?`

Answer 26

The effect of alcohol metabolism on the CNS and the cost of alcohol can lead to poor diet with low protein and low vitamins

Question 27

What are some common secondary diseases of alcohol dependence?

Answer 27

**- Wernicke-Korsakoff Syndrome** (thiamine deficiency leading to mental confusion and unsteady gait) **- Neurological Defects** (malabsorption of nutrients like Vit K and pyridoxine due to damage to GI tract) **- Chronic Pancreatitis** (constant pain in upper abdomen and back and weight loss) **- Type II Diabetes** (hyperglycaemia and glucosuria)

Question 28

What are two important signalling molecules from amino acids?

Answer 28

- NO from L-arginine - Hydrogen Sulphide from L-cysteine

Question 29

What are some of the signs of hyperammonaemia?

Answer 29

- Blurred vision, slurred speech, tremors, coma - Due to ammonia reacting with a-ketoglutarate with glutamate dehydrogenase to form glutamate in the mitochondria. No a-ketoglutarate for TCA

Question 30

Why do you get hyperammonaeima during renal failure?

Answer 30

Urea is not being filtered and excreted in the urine after diffusion from the liver. It is absorbed by the intestinal wall and the gut bacteria may back it down into ammonia

Question 31

Why do the accumulation of phenylketones in phenyketonuria cause brain development issues?

Answer 31

Similar structure to pyruvate so brain uptakes it but cannot use it

Question 32

Why does the build up of phenyalanine cause mental retardation?

Answer 32

Phenylalanine is a large neutral amino acid, saturates LNAA transporter at bbb barrier. Other LNAA are decreased in the brain so neurotransmitter synthesis is inhibited.

Question 33

What is the difference between cystine and cysteine, and homocysteine and homocystine?

Answer 33

**Cysteine =** AA **Cystine =** 2 x cysteine **Homocysteine =** homologue of cysteine **Homocystine =** 2 x homocysteine

Question 34

Why does homocystinuria affect connective tissue and what condition is it mistaken for?

Answer 34

**- Excess homocysteine** damages collagen and elastin by binding to lysine residue in proteins - **Metabolites of methionine** are toxic to neurones and cause neurological disfunction - Marfans

Question 35

How does the metabolism of alcohol damage the liver?

Answer 35

Question 36

What is oxidative stress?

Answer 36

Question 37

How is a respiratory burst produced?

Answer 37

Question 38

Answer 38

Question 39

How are amino acids degraded and what are the products of degradation?

Answer 39

Question 40

What processes produce ammonia in the body?

Answer 40

Question 41

How is ammonia transported around the body?

Answer 41

Ammonia is therefore used to transaminate pyruvate to produce alanine. The alanine is then transported in blood to the liver where it is converted back to pyruvate by transamination. The amino group is then fed via glutamate into urea cycle for disposal as urea and the pyruvate is used in gluconeogenesis to synthesise glucose which can be fed back to the tissues. The other amino acid utilised in a similar way is glutamine. Ammonia is combined with glutamate to form glutamine. Glutamine is then transported in blood to the liver or kidneys where it is cleaved by glutaminase to reform glutamate and ammonia. In liver the ammonia is fed into urea cycle for disposal as urea whereas in the kidney it is excreted directly in urine.