2- Protein And Amino Acid Metabolism

Question 1

• name some major nitrogen containing compounds

- what is creatinine, where is it excreted from and what can it be used as an indicator for?

Answer 1

• amino acids, proteins, purines & pyrimidine (DNA/RNA), creatine phosphate
• breakdown product of creatine and creatine phosphate, produced constantly (unless muscle is wasting)
• via kidneys
• provides estimation of muscle mass but more commonly used as indicator of renal function (raised levels indicate nephron damage).

Question 2

• how is N taken into the body and how is it removed?
• define positive & negative nitrogen balance
• describe protein turnover incl. how it’s ingested, metabolised for energy, stored and excreted.

Answer 2

• in via dietary protein and lost via hair, skin, nails or faeces and urine (mainly)
• positive N balance= input is greater than output, increase in total body protein (normal in growth and pregnancy)
• negative N balance= output greater than input, decrease in total body protein (never normal)
• protein in via diet or de novo aa synthesis, digested into free amino acids, then either synthesised to form protein muscle or go to liver to form amino acids excreted in urea or carbon skeletons to form 1. Glucogenic amino acids (eg glutamate) which then do gluconeogenesis for energy or 2. Ketogenic amino acids (eg lysine) which then form ketone bodies for energy

Question 3

• when are protein reserves mobilised & what hormones are responsible for this?
• what symptom of Cushing’s syndrome is due to excess protein breakdown?
• for the body to synthesise non essential aa’s, where does it get the C atoms from?
• where does ur get the amine group from?

Answer 3

• only under starvation; insulin=fed so increases synthesis and decreases degradation, glucagon=hungry so decreases synthesis and increases degradation
• cushings= excessive breakdown of protein bc of excess cortisol, weakens skin causing striae
• C from intermediates of glycolysis, Krebs or pentose phosphate pathway
• N from other aa’s via transamination or from NH3

Question 4

• name some specific amino acids & what they are needed for the synthesis of.
• define transamination and name the 2 key aminotransferase enzymes needed.
• define deamination and give an enzyme that does this.

Answer 4

• tyrosine (makes catecholamines, melanin, Thyroid hormones), cysteine (makes hydrogen sulphide), histidine (makes histamines), glutamate (makes GABA)
• Transamination= aminotransferase enzymes use alpha-ketoglutarate to funnel the amino group to glutamate (except aspartate aminotransferase which uses oxaloacetate to funnel amino group to aspartate). All require co factor derivative of Vit B6.
• enzymes= 1. Alanine aminotransferase (ALT) 2. Aspartate aminotransferase (AST) ALT &AST measured as part of liver function tests, higher in hepatitis etc
• deamination=liberates the amino group as a free ammonia, mainly in liver & kidney, NH3 then converted to urea and excreted. Enzymes=amino acid oxidases

Question 5

• describe urea & the principles of the urea cycle
• what are some possible defects is the urea cycle?
• why is ammonia toxic?

Answer 5

-high N content, not toxic, very water soluble, inert, excreted in urine
-in the liver, involves 5 enzymes, more protein diet= higher enzyme levels, cycle is inducible but not regulated refeeding
syndrome= if malnourished eat too fast, NH3 builds up fast and is toxic
-genetic disorders, loss of enzyme function, accumulation of NH3, causes nausea, vomiting, for longer can cause brain retard
-readily diffuses to the brain, interferes w aa & protein transport, pH effects, alters blood-brain barrier.

Question 6

• what are the 2 mechanism for the safe transport of aa N from tissues to liver for disposal?
• what are some clinical problems with amino acid metabolism? *phenylketonuria & homocystinuria *

Answer 6

1. Glutamine= NH3 combined w glutamate to form glutamine, transported in blood to liver where its cleaved by glutaminase to reform NH3 & glutamate. NH3 then enters urea cycle
2. Alanine= amine groups transferred to glutamate by transamination, pyruvate then transaminated by glutamate to form alanine, transported via blood to liver where its converted back to pyruvate by transamination. Amino group enters urea cycle.
   - over 50 diseases, total or partial loss of enzyme activity, heel prick test can identify some of these conditions
   - PKU= deficiency in phenylalanine hydroxylase so cannot convert phenylalanine into tyrosine (tyrosine needed for NA, adrenaline, TH pathways), instead phenylalanine is transaminated to phenyketones which accumulate in urine. Autosomal recessive. Diet= low phenylalanine, high tyrosine, avoid milk eggs etc
   - homocystinurias= problem breaking down methionine, methionine is converted to homocysteine normally, but homocysteine can’t form cysteine as enzyme cystathionine-beta-synthase doesn’t work therefore homocysteine & methionine accumulates, affects connective tissue and muscles, autosomal recessive. Diet= low methionine, cysteine and vitB6 + B12 supplements, folate supplements