Flashcards in Nitrogen Deck (32):
State the main nitrogen containing molecules in the body
Nitrogen is found mainly in amino acids, ammonia and urea within the body.
Describe the fate of dietary protein
Protein digestion can be split into 3 stages:
o Gastric - denaturation of proteins by HCl leaves them more open to the actions of pepsin to form peptide fragments
o Pancreatic - pancreatic enzymes create a mix of free amino acids and short peptides around 2-8 units in length
o Intestinal - free amino acids are absorbed into portal system. Di/tripeptides are also absorbed and broken down to free amino acids in the enterocytes of the brush border.
Describe the role of glutamate in the transfer of nitrogen to, between and from amino acids.
Glutamate is the only amino acid that can obtain its nitrogen from ammonia. All others obtain it from pre-existing amino acids through transaminase reactions, which involves the interconversion of a pair of amino acids and a pair of keto acids.
Each transaminase enzyme is specific for only 1 pair of amino acids and keto acids.
Describe the catabolism of protein.
Once broken down into individual amino acids, the remaining carbon skeletons can be further catabolised into intermediaries for the citric acid cycle and glycolysis, e.g. alanine -> pyruvate, aspartate ->oxaloacetate.
These intermediates can then be converted into glucose via gluconeogenesis. Note that this only applies for glucogenic amino acids.
Ketogenic amino acids can instead be catabolised for energy in the citric acid cycle, or instead be used to form ketone bodies.
Describe how nitrogen is transported through the plasma to the liver.
In the body, Nitrogen is transferred using glutamine and alanine. Nitrogen created from catabolised protein in muscles can be transported back to the liver as alanine, where it is built up into glucose once more. This process creates ammonia and urea in the liver, and also requires the use of the transferase enzymes to convert alanine into pyruvate or vice versa.
Why is nitrogen transported as glutamine and alanine instead of glutamate?
Nitrogen is transported as glutamine and alanine instead of glutamate for a few reasons
o Since glutamate has a net negative charge, transporting it would require an accompanying cation.
o This charge also means it does not pass readily through membranes.
o Alanine and glutamine bear no net charge.
Describe the formation of urea
Urea is formed from the ammonia that comes from several of the reactions involving amino acids.
Ammonia is formed through oxidative deamination, whereby glutamate loses its nitrogen as ammonia. This is captured and transformed into carbamoyl phosphate which is then fed into the urea cycle where it is converted into urea.
Describe the fate of the carbon of catabolised body protein.
Used for fatty acid synthesis, glucose or glycogen synthesis and cellular respiration.
Describe examples of how metabolic defects in the urea cycle give rise to clinical problems.
6 inherited disorders of the urea cycle
Most common is ornithine transcarbamoylase (OTC) deficiency (first enzyme in pathway, high ammonia levels). Unusual as X linked and not autosomal recessive
How do nitrogen fixing bacteria maintain low oxygen concentrations to allow the activity of nitrogen fixing nitrogenase?
Uncouple mitochondria to burn off O2
Differentiate into heterocyst that have O2 impermeable walls
Produce leghemoglobin to capture O2
Name two types of nitrogen fixing bacteria
Describe nitrogen fixation
Nitrogen fixation is a process in which nitrogen (N2) in the atmosphere is converted into ammonia (NH3) and ammonium cations (NH4+), which enter the soil for nitrification.
Follow nitrogen fixation, and involves the biological oxidation of ammonia or ammonium ions to nitrite (NO2) followed by the oxidation of nitrite to nitrate (NO3), which can be taken up by plants and microorganisms. Once the nitrate has been taken up, it is then converted back to ammonia.
What 4 amino acids are found in much higher concentrations, and why?
Glutamate - excitatory NT and vital for transamination
Alanine - major constituent of proteins
Aspartate - excitatory NT
Glutamine - taste (monosodium glutamate)
What is transamination?
Transfer of amino groups between molecules, seen in amino acid synthesis and degradation (reversible reaction)
What is required for transamination?
Pyridoxal phosphate (PLP) cofactor (made from vit B6)
What typically accepts amino groups in transamination?
What is the diagnostic value of aminotransferases?
Intracellular proteins, if in plasma suggests cell damage e.g. aspartate aminotransferase and alanine aminotransferase indicate liver diseasee
What reaction does alanine aminotransferase catalyse?
Alanine to pyruvate
What reaction does aspartate aminotransferase catalyse?
Aspartate to oxaloacetate
What cells secrete pepsin?
Chief cells in gastric epithelium, secreted as zymogen pepsinogen and activate by low pH
What do trypsin and chymotrypsin do?
Cut proteins and larger peptides into smaller peptides in the small intestine
What does aminopeptidases and carboxypeptidases do?
Membrane bound enzymes which degrade peptides into free amino acids in the small intestine
What is used to mark proteins for degradation?
Ubiquitin, targets proteins for degradation by the proteasome into peptide fragments
What disease can result from the ineffective removal of nitrogenous products from the body?
Gout - elevated levels of uric acid in blood, which crystallise and deposit into joints, tendons and surrounding tissues.
How is ammonia transported through the body?
As glutamate. Can also be converted to pyruvate following this to then make alanine, which can allow transport into the liver
Name the essential amino acids
What is the typical inheritance of inborn errors of metabolism (IEMs) disorders?
Autosomal recessive (enzyme deficiencies)
Receptor deficiencies are usually dominant
What are some common clinical features in IEMs?
Failure to thrive
Vomiting and refusal to feed
Describe an IEM associated with amino acid disorders
Phenylketonuria (PKU) = phenylalanine hydroxyls deficiency, increased toxic Phe levels which affects brain development
What are some clinical features of PKU?
Neonatal screening day 5 settled feeding
Phenylalanine levels increase following birth
Day 3-4 may be irritable and difficulty feeding
If untreated, delayed mental development and neurological features are evident by 6mo