Nitrogen

Question 1

What molecules contain nitrogen

Answer 1

AA and nucleotides

Question 2

Where do we get our nitrogen

Answer 2

Diet

Question 3

What is the fate of diatery proteins (give process)

Answer 3

Enzymatically hydrolysed:
* Pepsin cuts P into peptides in stomach
* Trypepsin and chymotrypsin cut P and larger peptides into smaller peptides in small intestine
* Aminopeptidase and Carboxypeptidases A and B degrade peptides into AA in small intestine

Question 4

What is the overall pathway of diatery protein degredation

Answer 4

Protein —> peptide —> AA

Question 5

Role of Carbs/fats and AA?

Answer 5

Carb/fats: provide energy
AA: building block for P

Question 6

Discuss the types of AA

Answer 6

20 AA:
* 11 = non-essential and are synthesised in the body
* 9 = essential - body can’t make so needed in diet (inc. phenylalanine)

Question 7

What could also happen to cellular proteins?

(catabolism of body protein)

Answer 7

Targeted for destruction if they are: misfolded, foreign or unwanted proteins - same end point as diatery P (individual AA, realasing energy)

Question 8

Explain what can happen with the Phenylketonuria (PKU)

Answer 8

Phenylalanine —-> tyrosine —-> thyroxine (/L-DOPA —> melanin/catecholamines

During step 1 BH4—->BH2 with enzyme phenyalanine hydroxase

If enzyme in insufficient supply/not made then tyrosine levels = low and alternative side metabilic pathway begins:
phenylalanine —> phenlpyruvate —->phenyllactate hydroxyphenylacetate/phenylacetate

End product= toxic and builds up = neurologically harmful

Question 9

What is PKU considered to be

Answer 9

Autosomal recessive disorder - cased from absence/deficiency of PAH and associated with inc Phe levels (toxic)

Question 10

What happens with out treatment for PKU and how can we treat it?

Answer 10

• Individual exhibits signs of impared brain development - now have neonatal screening programme (5 days)
• Quantitative AA analysis lead to findings: Dec P intake (but supplement other ones)from diet (target root cause) and supplement with tyrosine - managed by MDT

Question 11

Clincial features of PKU

Answer 11

Phe levels rise rapidly once feeding established, day 3/4 presents irratability/feeding difficulties
If untreated, delayed mental development and neurological features evident by 6 months
musty odour

Question 12

Protein catabolism diagram

Answer 12

Yep!

Question 13

Give brief sumary of conversion of NH4 to Urea

Answer 13

NH4 —(biosynthesis of AA, nucleotides, biological amines)—>Carbamoyl phosphate (—urea cycle–) same + urea (N excretion product)

Question 14

What is the urea cycle essentially?

Answer 14

A series of enzyme reactions

Question 15

What can be some defects of the urea cycle?

Answer 15

Rare group of inherited metabolic disorders (6) - most common = ornithine transcarbamoylase (OTC) which has X-linked inheritance, rest are autosomal recessive

Question 16

What are urea cycle defects (e.g. OTC) characterised by?

Answer 16

Hyperammonaemia (elevated ammonia level) - highly toxic and a medical emergency causing irreversiable neurological damage

Question 17

When do most urea cycle defects present?

Answer 17

newborn period

Question 18

What is the role of glutamate in transferring nitrogen to/from/between AA

Answer 18

(in urea cycle) α-ketoglutarate can collect nitrogen from other amino acids as a consequence of transamination reactions to yield glutamate. α-ketoglutarate can accept an amino group from NH4+ via the reversible glutamate dehydrogenase reaction to yield glutamate. - see diagram

Question 19

Where does the urea cycle occur?

Answer 19

Liver

Question 20

how is nitrogen transported through plasma to the liver

Answer 20

In skeletal muscle, the alanine-glucose cycle is commonly used for the transport of nitrogen from the skeletal muscle to the liver. In this process, ammonia from amino acid degradation is transaminated to form glutamate. Alanine aminotransferase (AST) will transaminate glutamate with pyruvate to generate alanine (and α -ketoglutarate). The alanine is released and transported to the liver where it will undergo another transamination to generate pyruvate, which is used as a substrate for glucose production (gluconeogenesis). The glucose is released from the liver and oxidized by the skeletal muscle.

Question 21

What is the fate of C in catabolised body proteins

Answer 21

The carbon skeletons resulting from the deaminated amino acids are used to form either glucose or fats, or they are converted to a metabolic intermediate that can be oxidized by the citric acid cycle.