Protein And Amino Acid Metabolism

Question 1

What happens to glucoagonic amino acids that are obtained from diet? give an example of one

Answer 1

contribute to gluconeogenesis and input into krebs cycle at many levels
eg tyrosine

Question 2

What happens to ketogenic amino acids? give an example of one

Answer 2

converted to ketone bodies and used for energy also

eg lysine and leucine

Question 3

What outputs and stores at there of N containing compounds?

Answer 3

stores:
- body proteins (2kg)
- amino acid poos (16g)
- n containing compounds (50g)
outputs:
- loss in hair, skin, nails, faces, urine

Question 4

What happens to the amino group from amino acids?

Answer 4

converted to ammonia and excreted

Question 5

When are protein reserves used for energy? What hormones promote degradation over synthesis and vica versa?

Answer 5

Only used in extream starvation
Insulin and growth hormone promote protein synthesis
Glucocorticosteroids and coritisol increase protein degradation

Question 6

Where does the carbon skeleton and amino group come from for amino acid synthesis?

Answer 6

carbon- glycolysis, pentose phosphate pathway, krebs intermediates
amino- provided by other amino acids by transamination or from ammonia

Question 7

Why are amino acids synthesised?

Answer 7

• protein synthesis
• neurotransmitters (serotonin from tryptophan, GABA from glutamate, NO from arginine)
• chemical signals (histamine from histidine, catecholamines from tyrosine)
• Heam
• creatinine ect all derive from amino acids

Question 8

What is transamination?

Answer 8

move the amine from one amino acid onto a ketoacid to create a new amino acid which can more easily be turned into urea and a new keto acid

Question 9

How do most aminotransferases work?

Answer 9

by moving the amino group from one amino acid onto alpha keto- gluterate to produce glutamate

Question 10

what does aspartate amino transferase do?

Answer 10

moves an amine group onto oxaloacetate to make an aspartate- needed in urea cycle

Question 11

What vitamin is needed for transamination?

Answer 11

A B6 derivative- pyridoxal phosphate

Question 12

What two amino transferases are released on injury to hepatocytes, what is their role?

Answer 12

alanine aminotransferase (ALT)- alanine into glutamate 
Aspartate amino transferase (AST)- converts amino group of glutamate into oxaloacetate to make aspartate

Question 13

When and where does deamination (liberating amino group as free ammonia rather than transamination) done?

Answer 13

in liver and kidneys

done when D- amino acids are digested from some foods (normal isomer is L- amino acids)

Question 14

Where does the urea cycle occur??

Answer 14

liver

Question 15

How is urea cycle controlled?

Answer 15

By expression of enzymes in urea cycle- high protein diet= high expression

Question 16

Why does ammonia toxicity occur in refeeding syndrome?

Answer 16

They go from very low protein diet (so low expression of urea cycle enzymes) to very high protein, but expression of the enzymes cannot increase fast enough to meet new demands of ammonia removal

Question 17

What inputs are there to the urea cycle?

Answer 17

glutamate, aspartate (all glutamate converted to aspartate by AST in first step), CO2, NH3, H20 and ATP

Question 18

What symptoms come with defects in urea cycle?

Answer 18

basically NH3 toxicity
severe disorders presents within 1 day of birth
mild may present in early childhood
vomiting, lethargy, irritability, mental retardation, seizures, coma

Question 19

What determines the severity of a urea cycle defect?

Answer 19

• Which of the 5 enzymes are absent
• How much the function of the enzymes is effected
• amount of protein eaten

Question 20

How is a urea cycle defect managed?

Answer 20

• low protein diet

- replace amino acids in diet with keto acids

Question 21

What effects does high ammonia have to body?

Answer 21

• diffuses into brain and is toxic
• interferes with amino acid transport and synthesis
• interferes with metabolism of neurotransmitters
• increases blood pH
• disrupts cerebral blood flow
• alters blood brain barrier
• interferes with krebs cycle

Question 22

What is normal blood conc of NH3?

Answer 22

25-40umol/L

Question 23

How is NH3 safely transported to liver and kidneys?

Answer 23

• Combine with glutamate to form glutamine to take it to liver/ kidneys where it is is reformed and fed into urea cycle
• Combine with pyruvate to form alanine which takes it to liver where transamination makes it into glutamate and pyruvate

Question 24

What is creatinine a clinical marker of?

Answer 24

• it is a breakdown product of creatine and creatine phosphate
• usually produced at constant rate (and is proportional to muscle mass), elevated when:
• exceedingly high muscle mass
• muscle atrophy
• damage to nephrons

Question 25

What is phenyl ketone uria? (PKU)

Answer 25

• autosomal ressesive dondtion where phenyl alanine hydroxylase is deficient
• This normally converts phenyl alanine into tyrosine to make catelachoamines (dopamine, adrenaline & noradrenaline, melanin ect)

Question 26

What is result of phenylketoneuria?

Answer 26

• phenylalanine builds up in blood
• it is transaminated to phenyl pyruvate
• is goes on to produce phenyl acetate and phenyllactate (ketones which are excreted in urine)
• Intellectual disability, developmental delay, microcephaly, seizures, hypopigmentation

Question 27

How can phenylketone uria be treated?

Answer 27

• remove phenyl alanine from diet (no artificial sweeteners, milk egg or cheese)
• tyrosine supplements
• heel prick test at birth

Question 28

How do phenyl alanine accumulations affect brain development?

Answer 28

• it is normally transported into brain by large neural amino acid transporter (LNAA)
• LNAA becomes saturated so other LNAAs cant get into brain
• Protein and other neurotransmitter synthesis is inhibited

Question 29

What is homocystinuria?

Answer 29

Methionine cannot be broken down due to defect in cystathione B- synthase, so cystenine not make but homocystine does accumulate

Question 30

Why does vitB12 and folate help reduce effects of homocysteineuria?

Answer 30

It promotes conversion of homocysteine (bad) into methionine (less bad)

Question 31

What is the effect of homocystine accumulations?

Answer 31

increased CVD risk
similar symptoms to marfans due to CT damage (Tall, short sight, skeletal deformities, high arched palate)
Neuro issues- seizures, developmental delay

Question 32

How is homocysteineuria treated?

Answer 32

low methionine diet (no nuts, milk, egg, cheese, fish, meat)

cysteine, floate, B12, B6 supplement

Question 33

How does alanine aminotransferase work?

Answer 33

moves amino group from alanine onto alpha ketogluterate to make glutamate