lecture 12 - nitrogen metabolism

Question 1

What are the sources of nitrogen in the body?

Answer 1

Dietary protein, natural protein turnover/body protein

Question 2

What are the uses of nitrogen in the body?

Answer 2

Neurotransmitters, coenzymes, amino acids/proteins, nucleotides

Question 3

What is the main form that nitrogen is in in the body?

Answer 3

Part of amino acids

Question 4

What is the difference between essential and non-essential amino acids?

Answer 4

The body can make non-essentials, but cannot make essentials so they need to be extracted from the diet

Question 5

What are conditionally essential amino acids, and what is the key example?

Answer 5

The body can synthesise them, however cannot make adequate amounts so require dietary top up in certain circumstances. Key example is arginine, which needs dietary supplementation during periods of growth.

Question 6

What is nitrogen balance dependent on?

Answer 6

Dietary nitrogen intake,
Physiological state

Question 7

What is the default state of nitrogen balance?

Answer 7

In balance - nitrogen intake and excretion are equal

Question 8

What are some causes of a positive nitrogen balance?

Answer 8

Growth of lean mass - Childhood/adolescent growth, pregnancy, body building

Question 9

What are causes of a negative nitrogen balance?

Answer 9

Starvation, illness (e.g. sepsis), burns, trauma

Question 10

What are the metabolic fates of amino acid carbon skeletons?

Answer 10

Skeletons are either glucagenic or ketogenic - form ketone bodies or glucose

Question 11

What form is nitrogen stored as waste product?

Answer 11

Urea

Question 12

Where is urea synthesised?

Answer 12

In the periportal hepatocytes of the liver

Question 13

Which 2 amino groups are used in nitrogen excretion?

Answer 13

Glutamine and alanine

Question 14

How is glutamine involved in nitrogen excretion?

Answer 14

1. In tissues, an additional amino group (NH3) can be added to glutamate via glutamine synthetase to form glutamine.
2. This stores more nitrogen, until the molecule reaches the liver where glutamine is converted back to glutamate via glutaminase
3. NH3 is released for conversion to urea then excretion.

Question 15

What enzyme converts glutamate to glutamine?

Answer 15

Glutamine synthetase

Question 16

What enzyme converts glutamine to glutamate?

Answer 16

Glutaminase

Question 17

What process occurs in periportal hepatocytes?

Answer 17

Glutamine is converted to glutamate via glutaminase, releasing an NH3 which is fed into the urea cycle

Question 18

What process occurs in perivenous hepatocytes?

Answer 18

Excess ammonia is captured by converting glutamate to glutamine, so that NH3 is not released into the circulation once it leaves the liver.

Question 19

What enzyme is required to remove an amino group from glutamate?

Answer 19

Glutamate dehydrogenase

Question 20

What is a transamination reaction?

Answer 20

Transferring an amino group from one amino acid to a keto acid, forming a new amino acid and the corresponding keto acid.

Question 21

What enzymes are required for transamination reactions?

Answer 21

Aminotransferases

Question 22

What is Phenylketonuria (PKU)?

Answer 22

A genetic phenylalanine hydroxylase enzyme deficiency

Question 23

What is the pathophysiology of PKU?

Answer 23

The deficiency in Phenylalanine hydroxylase prevents conversion of Phenylalanine to Tyrosine, leading to a build up of Phenylalanine and other toxic metabolites in the blood, and a deficiency of tyrosine

Question 24

What are the symptoms of PKU?

Answer 24

seizures, hair/skin hypopigmentation, intellectual disability, musty odour

Question 25

How is tyrosine deficiency implicated in the pathogenesis of PKU?

Answer 25

Tyrosine deficiency restricts that production of proteins and neurotransmitters that are essential for brain development and function.

Question 26

How is excessive phenylalanine implicated in the pathogenesis of PKU?

Answer 26

Phe saturates the blood brain barrier transporters, preventing transport of essential metabolites into the brain

Question 27

What is the non-pharmacological treatment for PKU?

Answer 27

Diet low in natural protein, or dietary supplementation with formulas with low Phe and high levels of essential amino acids

Question 28

What are the pharmacological interventions for for PKU?

Answer 28

Tyrosine supplementation, BH4 supplements to stabilise PAH enzymes,

Question 29

How is PKU typically diagnosed?

Answer 29

Screening test at birth with Guthrie card (heel prick)

Question 30

What are the issues typically faced by PKU patients?

Answer 30

Restrictive and expensive diet, poor palatability of diet/meds, termination of diet adherence in adolescence/adulthood, socially restrictive/isolating