Proteins and amino acid metabolism

Question 1

Major nitrogen containing compounds?

Answer 1

RNA, DNA, amino acids, proteins, creatine phosphate

Question 2

What is creatinine a breakdown product of?

Answer 2

Creatine and creatine phosphate in the muscle

Question 3

What is creatinine excretion proportional to and why?

Answer 3

Muscle mass because it is produces at a constant rate depending on muscle mass (unless wasting).
Also used as an indicator of renal function - (kidneys damaged if this is not being properly excreted)

Question 4

When is it normal to have a positive nitrogen balance?

Answer 4

Pregnancy
Normal state of growth
Recovering from malnutrition

Question 5

How do we lose/gain nitrogen from the body?

Answer 5

Lose: Skin, hair, nails
Faeces
Gain:
Diet

Question 6

What product does the liver covert the amino group (NH2) into to prevent ammonia being formed?

Answer 6

Urea which is excreted in urine

Question 7

Breakdown of amino acid carbon skeletons can be used to create? s can be used to create?

Answer 7

Glycogenic amino acid: glucose via gluconeogenesis

Ketogenic amino acids: ketone bodies

Question 8

Example of a glycogenic, ketogenic and both amino acid?

Answer 8

Glucogenic= alanine
Ketogenic= leucine
Both= tyrosine

Question 9

Protein reserves when starving mobilised by?

Answer 9

Hormones!
Insulin and growth hormone - increases protein synthesis, decreases protein degradation
Glucocorticoids (cortisol) Decreases synthesis, increases protein degradation

Question 10

What is Cushing’s syndrome?

Answer 10

• Excess cortisol - increased protein breakdown
• central obesity
• Weakens skin structure leading to striae

Question 11

Provide examples of conditionally essential amino acids

Answer 11

children and pregnant women (high rate protein synthesis) -argenine -tyrosine -cysteine

Question 12

Where do carbon atoms & amino groups for somatic synthesis of amino acids come from?

Answer 12

Carbon :
-Intermediates of glycolysis (3C)
-PPP (C4 & C5)
-Krebs cycle (C4 & C5)
Amino group:
-Other amino acids via transanimation
-ammonia

Question 13

Name 2 ingredients needed to make tyrosine?

Answer 13

-melanin -thyroid hormones

Question 14

2 main pathways that allow the safe disposal of nitrogen from amino acids? overview

Answer 14

-Transanimation (swapping amino group of amino acid with oxygen of keto acid)
-glutamate/aspartate is the new amino acid product
(can more readily feed into urea cycle
-deanimation - liberates amino acid group as free ammonia converted to urea and excreted

Question 15

What does an aminotransferase enzyme do?

Answer 15

transfer amino group of amino acid to something else

Question 16

Aminotransferase enzymes mostly use what to convert amino acids?

Answer 16

• a-ketoglutarate funnels amino group to glutamate

- (less common) –>oxaloacetate funnels amino group to aspartate

Question 17

Which vitamin do aminotransferases need to stay functional?

Answer 17

B6 - required for one of their coenzymes

Question 18

Key aminotransferase enzymes used to measure liver function are?

Answer 18

Alanine aminotransferase - ALT -converts alanine to glutamate
Aspartate aminotransferase- AST- converts glutamate to aspartate

Question 19

ALT/ AST raised in which conditions?

Answer 19

• Viral hepatitis
• Toxic liver injury
• Autoimmune liver diseases

Question 20

When is deanimation used to breakdown food?

Answer 20

-dietary D amino acids

Question 21

List 4 properties of Urea

Answer 21

• Non-toxic
• high nitrogen content
• most excreted in urine via kidneys
• performs osmotic roles in kidney

Question 22

Key facts for Urea cycle

Answer 22

Where? In liver
How many enzymes? 5
Enzymes regulated? By need - up/down regulated accordingly

Question 23

Impact of high/ low protein diet on the urea cycle?

Answer 23

High protein induces enzyme levels

Low protein/ starvation represses levels

Question 24

At what rate should you prescribe food if someone is experiencing refeeding syndrome?

Answer 24

Gradually reseed at 5/10 Kcal/kg/day

Question 25

Risks with refeeding patient?

Answer 25

-ammonia toxicity as the enzymes in the urea cycle have been down regulated

Question 26

Autosomal recessive genetic defects in the urea cycle can lead to what?

Answer 26

• hyperammonaemia (ammonia toxicity)

- accumulation/ excretion of urea cycle intermediaries

Question 27

Symptoms of issues with urea cycle (genetic/refeeding)

Answer 27

-vomiting -lethargy -irritability -mental retardation -seizures -comma (depends on amount protein in diet/ severity of symptoms)

Question 28

Management of issues with urea cycle

Answer 28

• low protein diet

- replace amino acids in diet with keto acids

Question 29

List 3 mechanisms that make ammonia toxic to cells

Answer 29

• interference with TCA cycle
• pH effects (ammonia is alkaline)
• interferes with blood-brain barrier

Question 30

List 2 mechanisms used for safe transport of amino acid nitrogen from tissues to liver for disposal

Answer 30

Glutamine
-ammonia + glutamate –> glutamine
-In liver cleaved by glutaminase to reform ammonia
-in liver ammonia –> urea cycle –> excreted
Alanine
-amine groups transferred to glutamate by transanimation
-pyruvate transanimated by glutamate to form alanine
-alanine to liver converted back pyruvate
-amino group into urea cycle
-pyruvate used to synthesise glucose

Question 31

Major potential symptom if metabolism issues not addressed

Answer 31

Intellectual impriment

Question 32

Treatment of amino acid metabolism issues

Answer 32

Strict diet, restricts certain amino acids

Question 33

Heel prick test looks for?

Answer 33

• CF
• Sickle cell
• inborn errors of metabolism

Question 34

What is PKU phenylketonuria?

• chemistry
• symptoms
• treatment

Answer 34

-deficiency in phenylalanine hydroxylase
-autosomal recessive
-accumulation of phenylalanine in tissue, plasma, urine
-phenylketones in urine = musty smell
Symptoms: intellectual disability -seizures -microcephaly
Treatment: strictly controlled low phenylalanine diet, enriched tyrosine
-avoid high protein foods

Question 35

What is homocystinurias?

• chemistry
• symptoms
• treatment

Answer 35

-problem breaking down methionine
-exces homocysteine excreted in urine
-autosomal recessive
-defect in cystathionine b synthase most common
symptoms: (caused by accumulation of methionine and homocysteine) impacts connective tissue, muscles, CNS
Treatment: low methionine diet, avoid nuts and high protein
cysteine, B6, B12 and folate supplement