Protein and Nitrogen Metabolism

Question 0

What happens to the a’a released from protein breakdown in the GI lumen?

Answer 0

-Absorbed into the bloodstream and enter the circulation to be used in protein synthesis and synthesis of N-containing compounds

Question 1

What is the first stage in protein metabolism and where does it occur?

Answer 1

-Lumen of GI tract
-Break down proteins into a’a by peptidases and proteases hydrolysing peptide bonds
-

Question 2

What effect do insulin and GH have a’a?

Answer 2

-Stimulates there uptake into skeletal muscle, adipose tissue and liver

Question 3

What effect does cortisol have on protein metabolism?

Answer 3

-Stimulates proteolysis

Question 4

What are the essential dietary a’a?

Answer 4

-lysine, isoleucine, leucine, methionine, threonine, valine , tryptophan, phenylalanine

Question 5

Define a’a pool

Answer 5

-Total amount of free a’a in the body

Question 6

Define nitrogen metabolism

Answer 6

-Metabolic processes which relate to N-containing compounds

Question 7

What is a’a reutilisation?

Answer 7

-approx.75% of a’a released during breakdown are used in synthesis

Question 8

What happens to the a’a that are not reutilised?

Answer 8

• Oxidised to release energy

- Synthesis of other N-containing compounds

Question 9

What is stage 2 of protein catabolism?

Answer 9

• NH2 removed from a’a

- Converted to intermediates of TCA cycle

Question 10

What is nitrogen balance?

Answer 10

-Nin=Nout

Question 11

What is the source of Nin?

Answer 11

-Proteins

Question 12

What is the source of Nout?

Answer 12

• Urea
• Urine
• Faeces
• Sweat
• Hair, nails skin

Question 13

When would there be a positive nitrogen balance

Answer 13

-During periods of growth

Question 14

When would there be a negative nitrogen balance?

Answer 14

-During periods of starvation, malnutrition and trauma

Question 15

What is protein turnover and what does its rate depend on?

Answer 15

• Breakdown and synthesis

- Depends on protein type, protein demand and varies with growth and ageing

Question 16

What is the approximate half-life of a protein?

Answer 16

-80 days

Question 17

Which a’a can be synthesised in the body?

Answer 17

Non-essential a’a

Question 18

What are the substrates for a’a synthesis?

Answer 18

• C atoms from pentose phoshate pathway and TCA cycle

- N from other a’a or transamination

Question 19

Where does a’a breakdown occur?

Answer 19

-Liver

Question 20

What happens to the C-containing compounds in a’a breakdown?

Answer 20

• Enter carb/lipid metaboism

- Converted to intermediates

Question 21

What is the first step in a’a breakdown?

Answer 21

• Transamination

- Deamination

Question 22

What happens to the majority of N in the body?

Answer 22

-Excreted as urea

Question 23

What is transamination?

Answer 23

-The removal of NH2 from an a’a by combination with a-ketoglutarate or oxaloacetate and transaminase enzymes which is transfer the NH2 to synthesise glutamate or asparatate and a keto-acid (depending on the starting a’a)

Question 24

What are the two possible equations for transamination?

Answer 24

- a'a+a-ketoglutarate->glutamate + keto acid | - a'a+oxaloacetate->aspartate +keto acid

Question 25

Why is transamination useful if it just produces other a'a?

Answer 25

-Aspartate and glutamate can enter the urea cycle for excretion

Question 26

What are two clinical important transaminase enzymes and why?

Answer 26

- alanine aminotransaminase - aspartate aminotransaminase - Can be used as a measure of liver function -> High levels indicates liver damage

Question 27

What effect does cortisol have on transaminases?

Answer 27

-Stimulates their production in the liver

Question 28

What is deamination?

Answer 28

-The removal of NH2 from a'a to free NH3

Question 29

What is NH3?

Answer 29

-Ammonia

Question 30

What happens to NH3?

Answer 30

-Spontaneously ionised to NH4+

Question 31

Why is NH3 a problem?

Answer 31

- Reduces the TCA cycle | - Effects neurotransmitter synthesis

Question 32

What are the toxicity problems of NH4+?

Answer 32

- Blurred vision - Tremors - Coma - Death

Question 33

How is NH3 removed from the body?

Answer 33

-Converted to urea and excreted

Question 34

What enzymes are responsible for deamination? (umberella term)

Answer 34

-L-/D-a'a oxidases

Question 35

Where does deamination occur?

Answer 35

-Liver/Kidney

Question 36

Which a'a does ALT convert?

Answer 36

-Converts Alanine to glutamate + ketoacid

Question 37

Which a'a does AST convert?

Answer 37

-Glutamate ->aspartate+ketoacid

Question 38

Why is urea better than NH3?

Answer 38

- High N content for excretion - Non-toxic - Water-soluble so can travel in blood - Chemically inert in humans - Useful osmotic effects in kidney tubules

Question 39

Where does the urea cycle occur, specifically?

Answer 39

-Partly in the cytoplasm and partly in the mitochondrial matrix of hepatocytes

Question 40

How many enzymes are involved in the urea cycle?

Answer 40

5

Question 41

What is the purpose of the urea cycle?

Answer 41

-To remove NH3 and NH4+ which are toxic to the body

Question 42

From where is urea excreted?

Answer 42

-In urine via the kidneys (urea diffuses from the liver into the blood)

Question 43

What happens to the urea which is reabsorbed from the kidney tubules?

Answer 43

-Enters small intestine and is processed by bacteria which produces ammonia

Question 44

What are the substrates for the urea cycle?

Answer 44

- NH4+ from deamination - NH3+ from the GI lumen and from the breakdown of excess glutamine - Aspartate and Glutamate from transamination

Question 45

What are the two mechanisms of NH3 excretion?

Answer 45

- Converted to glutamine via Glutamate+NH3->glutamine | - Converted to urea

Question 46

How is glutamine excreted?

Answer 46

-Directly in the urine via kidneys

Question 47

What happens to excess glutamine which is not excreted via kidneys?

Answer 47

-NH3 is converted to urea

Question 48

What enzyme catalyses NH3 incorporation with glutamate?

Answer 48

-Glutamine synthase

Question 49

Describe the regulation of the urea cycle, and state in what situation this can be a problem

Answer 49

- No negative feedback from product as aim is to excrete urea - Inducible enzymes -> high protein diet -> high urea enzymes - Can cause refeeding syndrome; in people with low protein metabolism such as marasmus, giving protein rich food can lead to death as the ammonia in the body will rise, and conversion to urea will not be adequate due to lack of enzymes, leading to toxicity and death

Question 50

What is the clinical picture of NH3 toxicity?

Answer 50

- Vomiting - Lethargy - Irritability - Mental retardation in children - Seizures - Coma

Question 51

What happens if there is a complete loss of a urea enzymes?

Answer 51

- Fatal | - Death

Question 52

What is the treatment of urea enzyme defects?

Answer 52

-Reduction in the intake of a'a

Question 53

What type of inheritance in phenylketouria?

Answer 53

-Autosomal recessive

Question 54

What is the enzyme deficiency in phenylketouria?

Answer 54

-Phenylalanine hydroxylase

Question 55

Where is the gene located for phenylalanine hydroxylase?

Answer 55

-Chromosome 12

Question 56

What is the incidence of phenylketouria?

Answer 56

-1 in 15,000

Question 57

Is phenylketouria used in a standard screening test in neonates?

Answer 57

-Yes, heel prick test

Question 58

What is the normal metabolism of phenylalanine?

Answer 58

-Phenylalanine->tyrosine via phenylalanine hydroxylase

Question 59

What happens in phenylketouria?

Answer 59

- Phenylalanine hydroxylase absent - Phenylalanine accumulates in blood and tissues - Converted to Phenylpyruvate (phenylketone)

Question 60

How are phenylketones excreted and how can this be used in diagnosis?

Answer 60

- Excreted in the urine | - Test for phenylketones in urine

Question 61

Why is phenylpyruvate problematic?

Answer 61

-Inhibits pyruvate uptake into the mitochondria

Question 62

Why is phenylketouria a problem in relation to tyrosine?

Answer 62

- Tyrosine used to synthesis adrenaline,noradrenanline and dopamine - Deficiency in dopamine results in disruption of CNS development in children if untreated

Question 63

What inheritance pattern is homocysteinuria?

Answer 63

-Rare autosomal recessive

Question 64

What is the enzyme deficiency in homocystinuria?

Answer 64

-Cystathione-b-synthase

Question 65

What is the normal metabolism of homocystiene?

Answer 65

- Homocystiene->Cystathione via cystathione-b-synthase | - Cystathione->Cysteine

Question 66

What cofactor does cystatione-b-synthase need?

Answer 66

-Vitamin B6

Question 67

What happens in homocystinuria?

Answer 67

- No cystathione-b-synthase - Homocysteine begins to accumulate in blood->oxidised to homocystine - Homocysteine also converted to methionine via vitamin B12

Question 68

Why is conversion to methionine better than oxidation to homocystine?

Answer 68

-Although methionine is damaging, homocystine accumulation in the blood can lead to chronic disorders of connective tissue, muscles, CNS and CVS

Question 69

How does chronic homocystine lead to connective tissue damage?

Answer 69

-Disrupts the bonds in the fibrillin-1-protein which is an important connective tissue protein

Question 70

What CVS problems can homocystinuria cause?

Answer 70

-Angina by the age of 30 via an unknown mechanism

Question 71

What are two important signalling molecules resulting from a'a metabolism?

Answer 71

- Nitric oxide (vasodilator and neurotransmitter) | - Hydrogen sulphide (Vasodilator)