L2: origin of waste products Flashcards
Two categories of elimination/excretion
Xenobiotics - foreign substances
Endobiotics - metabolic end products
Examples of xenobiotics and how they are eliminated
Drugs, flavourings and colourings, plant pigments, plant poisons, etc.
Eliminated by modification and conjugation (to glucuronides/sulphates)
Both to increase the water solubility to be able to eliminate
Examples of endobiotics and how they are eliminated
Urea (from proteins and a.a.); creatinine (from creatinine phosphate); uric acid (from nuclei cancer acids); urobilin (from heme/bilirubin): metanephrine (VMA) (from epinephrine, norepinephrine); various sulfates (from steroid hormones)
Eliminated by the kidneys to prevent toxicity due to their accumulation.
CO2 from carbohydrate and fat metabolism but eliminated via the lungs.
What does ureotelic meant?
Human are ureotelic = we excrete excess protein-derived nitrogen as urea
Stages in urea biosynthesis
- Transamination
- Oxidative deamination
- Ammonia transport
- Urea cycle
- Transamination
Surplus of amino acids must be transaminated = the movement of the alpha amino group onto alpha-ketoglutarate
Individual enzymes catalyse the reaction
This converts alpha-ketoglutarate into glutamate, and the remaining amino acid is an alpha-ketoacid
Freely reversible
- Oxidative deamination
Oxidative deamination is catalysed by glutamate dehydrogenase
Uses NAD+ to pass along the alpha-amino group from glutamate, leading to reduction and production of NADH (which goes off to the electron transport chain) and releases the amino group as ammonia in ion form - NH4+
- Ammonia transport
Ammonium is toxic at 0.1-0.2mM (can inhibit brain TCA enzymes and the synthesis of neurotransmitters) so it is catalysed into non-toxic glutamine for transport to the liver
Glutamine synthesis:
Glutamate + NH4+ + ATP —> glutamine + ADP + Pi
Catalysed by glutamine synthase (GS)
Occurs for most tissues except muscles in which alanine is formed.
Pic at min 24.
- Urea cycle
In the liver, ammonia is converted to urea in an ATP-dependent set of 5 catalysed reactions. (Do not need to know the cycle)
Properties of urea
- principal (~85%) end product of nitrogen metabolism
- non-toxic
- uncharged, water-soluble, low molecular weight
- filtered and excreted gradually by the kidneys
- CO(NH2)2
Urea excretion
- around 12-20g excreted per day via the kidneys
- it varies due to many factors so is not a reliable indicator of kidney function
Brief - what is creatinine clearance
Creatinine clearance (CrCl) is a commonly use fair estimation of GFR in healthy subjects
Uric acid excretion
- nucleic acid degradation yields purine and pyramiding nucleotides
- purines (A+G) break down enzymatically to produce uric acid
- low solubility
- uric acid is filtered by the glomerulus but is reabsorbed and secreted by the tubules
- kidneys filter 60-70% of uric acid, but results in about 10% of the total filtered being finally excreted under normal circumstances
- at physiological pH uric acid exists largely as urate ions, but sodium urate is not very soluble. It comes out of solution if concentration rises (gout) or the pH falls (kidney stones).
- deficiency in some enzymes results in overproduction of uric acid in men - gout
Pigments of waste product - urobilinogens and urobilins excretion
Pigments of urines and of stools
Natural RBC breakdown releases lots of heme by spleen macrophages. Heme breaks down into iron and a ring - the ring is converted into bilirubin, a very hydrophobic poorly soluble molecule. This is metabolised and excreted.
Bilirubin metabolism
- Unconjugated bilirubin is carried by albumin and enters the liver.
- It gets conjugated with sugars to solubilised them for excretion, forming bilirubin glucuronide.
- It is passed through bile ducts into SI and then LI. Bacteria strip the sugars and metabolise urobilinogen, and oxidised leading to stercobilin (stools pigment)
There is a shunt which sends across some of the urobilinogen into the kidneys, which is oxidised into urobilin (urines pigment)
