Week 5- nitrogen metabolism

Question 1

What is nitrogen an essential constituent of?

Answer 1

Ribonucleic acid (RNA, DNA) and protein

Question 2

What is the sum of nitrogen intake and excretion?

Answer 2

Dietary nitrogen intake= nitrogen excretion

Question 3

What is the major dietary source of nitrogen?

Answer 3

Protein

Question 4

Where is our reservoir of nitrogen stored?

Answer 4

Muscle

Question 5

When do we see negative nitrogen balance?

Answer 5

Catabolic states such as malnutrition, diets, infection, cell toxicity

Question 6

What is the main nitrogen excretion product?

Answer 6

urea

Question 7

How do we get urea from amino acids?

Answer 7

• The carbon skeleton is the primary synthetic source
• Carbon skeleton catabolised to carbon dioxide and water: produces energy
• catabolism of this produces ammonium ions
• they are toxic therefore the detoxification process converts them to urea - uses energy

Question 8

Why are transamination reactions central to amino acid metabolism?

Answer 8

To utilise the carbon skeleton of amino acids for synthesis and energy production

Question 8

Why are transamination reactions central to amino acid metabolism?

Answer 8

To utilise the carbon skeleton of amino acids for synthesis and energy production

Question 9

What is transamination?

Answer 9

Transfer of the amino group of one amino acid to a 2-oxo acid (keto acid) with formation of the corresponding amino acid and 2-oxo acid

Question 10

What does transamination require as a co factor?

Answer 10

B6- pyridoxal phosphate

Question 11

What is schiff base formation?

Answer 11

Shiff base formation with active site locked pyridoxal phosphate is a common mechanism in amino acid metabolism

Question 12

What happens to children who have a defect in the urea cycle?

Answer 12

• typically show symptoms after the first 24h of life: irritable, refuse feeding followed by vomiting lethargy and then seizures and respiratory alkalosis, coma may occur
• if untreated they will die
• caused by rising ammonia levels in the blood
• OTC and CPS deficiency
• also citullenemia

Question 13

How can we mitigate the need to produce 22g urea/day?

Answer 13

• Reduce nitrogen intake -protein restriction
• increase nitrogen excretion by activating alternative pathways to the urea cycle
• minimise protein catabolism, maximise protein anabolism
• Restriction of NEAA
• supplement of EAA and EKA- essential amino acids
• pharmacology needed- sodium benzoate etc

Question 14

What is the biochemistry of Ornithine trancarbamylase (OTC) deficiency ?

Answer 14

Failure to excrete nitrogen

• arginine becomes an EAA
• treatments now but used to be fatal almost

Question 15

How do we activate alternative nitrogen excretion pathways?

Answer 15

• Sodium benzoate- activated by coenzyme A and conjugates with glycine, in the liver and kidney, to produce hippuric acid which is efficiently excreted by the kidney
  2. Sodium phenyllbutyrate

Question 16

What happens if phenylalanine is defective?

Answer 16

PKU

• autosomal recessive disorder
• 1/10000
• Phenylalanine concentration increases and cannot be converted into tyrosine
• tyrosine becomes an essential amino acid
• severe mental symptoms if not treated
• increased phenylalanine inhibits tyrosine metabolism re-inforcing a tyrosine deficiency state
• fair hair, blue eyes- lack of melanin
• treatment is restricting phenylalanine and supplementing other amino acids- for life