Nitrogen Flashcards
What molecules contain nitrogen
AA and nucleotides
Where do we get our nitrogen
Diet
What is the fate of diatery proteins (give process)
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
What is the overall pathway of diatery protein degredation
Protein —> peptide —> AA
Role of Carbs/fats and AA?
Carb/fats: provide energy
AA: building block for P
Discuss the types of AA
20 AA:
* 11 = non-essential and are synthesised in the body
* 9 = essential - body can’t make so needed in diet (inc. phenylalanine)
What could also happen to cellular proteins?
(catabolism of body protein)
Targeted for destruction if they are: misfolded, foreign or unwanted proteins - same end point as diatery P (individual AA, realasing energy)
Explain what can happen with the Phenylketonuria (PKU)
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
What is PKU considered to be
Autosomal recessive disorder - cased from absence/deficiency of PAH and associated with inc Phe levels (toxic)
What happens with out treatment for PKU and how can we treat it?
- 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
Clincial features of PKU
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
Protein catabolism diagram
Yep!
Give brief sumary of conversion of NH4 to Urea
NH4 —(biosynthesis of AA, nucleotides, biological amines)—>Carbamoyl phosphate (—urea cycle–) same + urea (N excretion product)
What is the urea cycle essentially?
A series of enzyme reactions
What can be some defects of the urea cycle?
Rare group of inherited metabolic disorders (6) - most common = ornithine transcarbamoylase (OTC) which has X-linked inheritance, rest are autosomal recessive
What are urea cycle defects (e.g. OTC) characterised by?
Hyperammonaemia (elevated ammonia level) - highly toxic and a medical emergency causing irreversiable neurological damage
When do most urea cycle defects present?
newborn period
What is the role of glutamate in transferring nitrogen to/from/between AA
(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
Where does the urea cycle occur?
Liver
how is nitrogen transported through plasma to the liver
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.
What is the fate of C in catabolised body proteins
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.
