Protein Degradation and Nitrogen Disposal Flashcards
Briefly outline the process of converting dietary protein to amino acids
- In the stomach, Pepsin breaks down structural proteins into polypeptides (PEPsin into polyPEPtides).
- In the small intestine, proteases break the polypeptides into short peptides.
- Still in the small intestine, amino-peptidases break the short peptides into di/tri peptides and amino acids.
* Di/Tri peptides are uptaken by a hydrogen-linked secondary active transporter.
* Single amino acids are uptaken by a sodium-linked secondary active transporter.
What are the roles and fates of amino acids?
Amino acids have many roles and fates, and are a great example of how the body can scavenge and synthesise to meet its needs.
Roles - building block of protein (including tissue), nucleotides, hormones, neurotransmitters, and co-enzymes.
They can also be converted into acetyl-CoA, which can be further converted into ketone bodies, or enter TCA cycle for energy use or storage as glycogen.
What is the nitrogen balance equation?
A summary of the nitrogen released from the body’s intake and use of amino acids. In the process of using amino acids, nitrogen is released as ammonia, converted to urea, and excreted.
Positive nitrogen balance (intake exceeds excretion) is seen in pregnant women, growing children, and bodybuilders (i.e. healthy/growing people).
Negative nitrogen balance is seen is those with a protein deficient diet, a chronic infection, and cancer (i.e. sick/wasting away people).
What happens when an amino acid is recycled?
The amine moiety is removed, and eventually excreted as urea. The remnant carbon skeleton is used for biosynthesis and/or energy production.
What is transamination (inter-conversion)?
Need to know reactions and examples for exam
Transamination is a process the body undertakes to funnel various amino acids into one of three different types, which are then processed further. It involves the transition of an amine group from one molecule to another.
The three ‘funnels’ are keto-acids called AMINO-TRANSFERASES, which work by converting the existing amino acid into a keto-acid, while converting themselves into one of the three amino acids (Alpha-KG->Glutamate, OAA->Aspartate, Pyruvate->Alanine). This is achieved by ‘swapping’ the keto-acid’s ketone group with the amino acid’s amine group.
This is a key efficiency strategy, as the body now only needs to process 3 amino acids, rather than the 20 that naturally occur.
What is Oxidative Deamination?
(Need to know for exam).
Oxidative deamination is a process that involves converting an amino acid to its corresponding keto-acid, releasing NH3. It primarily occurs in the liver (and kidneys), and involves the conversion of glutamine to glutamate, and glutamate to alpha KG, as well as alanine to pyruvate. Of these, glutamate->alpha-KG is most common, with the enzyme GLUTAMATE DEHYDROGENASE.
All of these reactions require NAD, and release NH3 and NADH.
Outline the fate of nitrogen in the body.
Nitrogen is released as NH3 during deamination. In normal pH, ammonia is in equilibrium with H+ to produce ammonium (NH4+). Both these substances are highly toxic, and would affect the body’s pH if not excreted.
While NH4+ can be released by the kidneys, most (86%) N excretion is through Urea, which is created in the liver.
Key points:
Urea Cycle split between mitochondria and cytosol.
Entry Point 1 - Committed step (mitochondria). NH3+CO2+O2 (plus 2ATP) form CARBAMOYL PHOSPHATE which enters the Urea Cycle.
Entry Point 2 (cytosol) - N-group on ASPARTATE following transamination (related to TCA cycle). Carbon skeleton expelled/recycled as fumarate.
Regulation - primarily via carbamoyl-phosphate SYNTHASE, which is activated by NAG (allosteric). There is also a link to the TCA cycle (incoming via aspartate, outgoing via fumarate).
What is a Carbon Skeleton and what is its fate?
The carbon skeleton is the remnants of an amino acid after the amine moiety is removed. There are two fates for Carbon skeletons:
GLUCOGENIC skeletons are degrated to pyruvate and recycled to form glucose during GLUCONEOGENESIS
KETOGENIC skeletons are recycled to form ketone bodies.
What is the role of liver in amino acid metabolism?
Most catabolic enzymes for amino acids are found in the liver (therfore primary site of catabolism - only dietary GLN/GLU are metabolised by intestine, rest of glucose, amino acids and fat passes through).
In particular, alanine travels to the liver for conversion to pyruvate and gluconeogenesis, and circulating GLU/GLN are broken down in the liver, releasing NH3, which is converted to harmless urea in the liver.
What is the role of kidney in amino acid metabolism and pH regulation
Nitrogen excretion - The kidney can excrete NH3 directly from the blood, assisting the body’s pH balance, it is also the excretion site for urea.
In starvation situations, the kidneys can undertake RENAL GLUCONEOGENESIS (making of glucose from carbon skeletons), helping the liver out.
What is Glutamine and why is it useful?
Glutamine is a molecule formed when Glutamine Synthase acts on glutamate. It is the most common of the three funnel routes, and is useful as it is non-toxic yet carries two NH3 groups, allowing the body to tolerate a lot of nitrogen. It is also very useful for building cells and is destined for the liver.
