Protein and Amino Acid Metabolism

Question 1

Where does stage 1 of catabolism of proteins occur and what enzymes are involved

Answer 1

Occurs in the GI tract

Proteases and peptidases break protein down into amino acids which are absorbed

Question 2

What molecules stimulate uptake of protein into cells and what molecule stimulates breakdown of proteins

Answer 2

Uptake - insulin and growth hormone

Breakdown - cortisol

Question 3

What are the types of amino acids

Answer 3

Ketogenic

Glucogenic

Ketogenic and Glucogenic

Question 4

How are amino acids catabolised

Answer 4

Amino group removed and converted to urea

Remaining C-skeleton converted to one or more of: pyruvate, oxaloacetate, fumarate, alpha-ketoglutarate, succinate CoA, acetyl CoA, acetoacetyl CoA

Question 5

Why are amino acids described as Ketogenic and what can they be used to synthesise

Answer 5

They produce acetyl CoA when catabolised (or acetoacetyl CoA)

Acetyl CoA then used to make ketone bodies or fatty acids

Question 6

Why are amino acids described as Glucogenic and what can they be used to synthesise

Answer 6

They produce other products (not acetyl CoA) when catabolised

Synthesise glucose or glycogen

Question 7

What are the terms used to describe the intake of nitrogen against loss of nitrogen

Answer 7

N-balance - where intake equals loss

Positive N-balance - intake is greater than loss

Negative N-balance - intake less than loss

Question 8

When would a person have positive N-balance and when would they have negative N-balance

Answer 8

Postive N-balance - active growth, pregnancy, tissue repair, convalescence

Negative N-balance - starvation, malnutrition, trauma

Question 9

What are the essential amino acids

Answer 9

Isoleucine

Lysine

Threonine

Histidine

Leucine

Methionine

Phenylalanine

Tryptophan

Valine

Question 10

Which amino acids are conditionally essential and under what circumstances are they essential

Answer 10

Arginine - during periods of active growth (body can synthesise small quantity)

Tyrosine - if diet low in phenylalanine (synthesised from it)

Cysteine - if diet low in methionine (synthesised from it)

Question 11

Why is a regular and adequate supply of protein needed in the diet

Answer 11

To replace the amino acids that are not reutilised after protein breakdown

Question 12

What are the two signalling molecules synthesised from amino acids

Answer 12

Nitric oxide from L-arginine

Hydrogen sulphide from L-cysteine

Question 13

What are the three features of amino acid breakdown

Answer 13

C-atoms converted to intermediates of carbohydrate and lipid metabolism

Start with removal of NH₂ group by transamination of deamination)

N-atoms usually converted to urea

Question 14

What are the two ketogenic only amino acids

Answer 14

Leucine

Lysine

Question 15

Which amino acids are both glucogenic and ketogenic

Answer 15

Isoleucine

Tyrosine

Phenylalanine

Tryptophan

Question 16

Which enzymes are involved in transamination and what stimulates their synthesis

Answer 16

Aminotransferases

Cortisol

Question 17

Which molecules can be used in transamination as keto acid 2 and what are they converted to

Answer 17

Alpha-ketoglutarate - converted to glutamate

Oxaloacetate - converted to aspartate

Question 18

Which two tranaminases are clinically important and why

Answer 18

Alanine aminotransferase (ALT)

Aspartate aminotransferase (AST)

Important as used when assessing liver function - measured in serum

Question 19

What is deamination and which groups of enzyme are involved

Answer 19

Removal of the NH₂-group as a free NH₃

L and D-amino acid oxidases - convert amino acids to keto acids and NH₃

Question 20

What are the importance of D-amino acid oxidases

Answer 20

Convert D-amino acids into keto acids as D-amino acids cannot be used for protein synthesis as they are the wrong optic isomer

Question 21

What does glutaminase do

Answer 21

Converts glutamine to glutamate and NH₃

Question 22

Why is glutamate dehydrogenase important

Answer 22

Involved in disposal of amino acids and synthesis of non-essential amino acids

Produces alpha-ketoglutarate from glutamate

Question 23

When do disorders of amino acid metabolism usually have a clinical consequence

Answer 23

When affected enzyme is involved in amino acid breakdown

This is because it allows the amino acid to accumulate and the AA may be toxic itself and/or be metabolised to toxic products

Restrict amount of amino acid in diet

Question 24

What is phenylketonuria/PKU

Answer 24

Inherited metabolic disorder where urine contains large amounts of phenylketones produced from phenylalanine

Usually there is defect in phenylalanine hydroxylase and as a result phenylalanine accumulates in tissues and blood

Phenylalanine is metabolised by other pathways to produce other products, including phenylpyruvate

Question 25

What are the consequence if PKU is left untreated

Answer 25

Inhibition of brain development as phenylpyruvate inhibits pyruvate uptake into mitochondria, interfering with energy metabolism in the brain Associated with seizures, microcephaly

Question 26

How do you test for PKU

Answer 26

Heel prick test shortly after birth

Question 27

What is homocystinuria

Answer 27

Inherited autosomal recessive defect in methionine metabolism, in which Type 1 is cauesd by deficiency in cystathionine beta-synthase (CBS) enzyme CBS normally converts homocysteine to cystathionine which is then converted to cysteine Homocysteine levels rise and some can be converted to methionine

Question 28

How is homocystinuria usually detected

Answer 28

Elevated levels of homocysteine and methionine in the plasma Homocytine in the urine

Question 29

What can homocystinuria cause

Answer 29

Disorders of connective tissue, muscle, CNS, cardiovascular system Due to chronic elevated plasma levels of homocysteine

Question 30

What is the mechanism behind ammonia's toxicity

Answer 30

Reacts with alpha-ketoglutarate to form glutamate in mitochondria via glutamate dehydrogenase This removes alpha-ketoglutarate from TCA cycle, slowing it This disrupts energy supply to brain cells May affect pH inside cells of CNS and may interfere with neurotransmitter synthesis and release

Question 31

What are the clinical effects of hyperammonaemia

Answer 31

Blurred vision Tremors Slurred speech Coma Death Interference with amino acid transport and protein synthesis Disruption of cerebral blood flow Alkaline effects Interference with metabolism of excitatory amino acid neurotransmitters Alteration of blood brain barrier Interference with TCA cycle

Question 32

How can ammonia be detoxified

Answer 32

Used in synthesis of N-compounds - glutamate Conversion to urea and excreted Ammonia can be excreted directly in urine

Question 33

Describe glutamine synthesis

Answer 33

Synthesised from ammonia and glutamate via glutamine synthetase

Question 34

How is glutamine synthesis used to combat ammonia toxicity

Answer 34

Glutamine is synthesised using ammonia in cell and is then released where it is transported to the liver and kidney Glutamine is then hydrolysed by glutaminase releasing ammonia which can be excreted in urine or converted to urea

Question 35

How is alanine used in ammonia detoxification

Answer 35

Pyruvate transaminated in tissue by glutamate to produce alanine Alanine travels in blood to liver In liver amine group transferred to glutamate and pyruvate produced from reaction which can travel back to tissues to be used again

Question 36

How is urea synthesis regulated and what condition is associated with giving too much protein quickly to malnourished patients

Answer 36

Enzymes of the cycle are inducible with high protein diet inducing the enzyme and vice versa Refeeding syndrome is caused by giving too much protein too soon to malnourished as the excess amino acids are degraded leading to hyperammonaemia

Question 37

Describe the inherited diseases of the urea cycle

Answer 37

A set of autosomal recessive diseases affecting one of the enzymes in the cycle Can only be partial loss of the enzyme as full loss is fatal

Question 38

What are the symptoms of inherited diseases of the urea cycle

Answer 38

Vomiting Lethargy Irritability Mental retardation Seizures Coma

Question 39

What is the treatment for diseases of the urea cycle

Answer 39

Low protein diets Diets where keto acids of essential amino acids are used to replace the amino acids themselves

Question 40

When might hyperammonaemia develop as a secondary consequence

Answer 40

Due to liver disease like cirrhosis Liver's ability to remove NH₃ from portal blood is impaired

Question 41

What happens to urea in the body

Answer 41

Most is filtered and excreted in the urine A small amount crosses the intestinal wall, entering intesine where bacteria then break it down releasing ammonia that can be reabsorbed