MEH 2 - Protein + Amino Acid Metabolism Flashcards
What are the 3 major nitrogen containing compounds in the body?
How much Nitrogen is in the body, how do we gain/lose N from the body?
When is a positive positive N balance and a negative N balance normal?
- AA’s, Proteins + DNA/RNA Bases (purines/pyrimidines)
- 2kg N in body proteins, taken in through diet, lost in faeces + urine
- Positive (input>output) = normal state in growth/pregnancy/adult recovering from malnutrition
- Negative (output>input) = never normal, causes include trauma/infection/malnutrition
How is creatinine produced?
What is creatinine a clinical marker for?
- Breakdown product of creatine + creatine phosphate. Produced at a constant rate, dependent on/proportional to muscle mass. Filtered by kidneys into urine.
- Estimate of muscle mass + indicator of renal damage (raised upon damage to nephrons)
What is the difference between glucogenic and ketogenic amino acids? Give an example of each.
- Ketogenic = can be degraded directly into Acetyl CoA, which is a precursor for ketone bodies. E.g.: phenylalanine
- Glucogenic = can be converted into glucose via gluconeogenesis, E.g.: alanine
When does mobilisation of protein reserves occur?
What hormones control this + what are their effects on protein synthesis + protein degradation?
In what condition does excess cortisol cause excessive protein breakdown?
- During extreme stress (starvation)
- Insulin + GH = Increases PS/decreases protein degradation.
- Glucocorticoids = e.g.: cortisol, Decreases PS, increases protein degradation.
- Cushing’s syndrome (leads to striae, look like stretch marks)
What are the 9 essential AA’s?
What 3 AA’s are “conditionally” essential in children and pregnant women?
- Isoleucine, Lysine, Threonine, Histidine, Leucine, Methionine, Phenylalanine, Tryptophan + Valine. (If learnt this huge list may prove truly valuable)
- Arginine, Tyrosine + Cysteine.
Where do carbon atoms for non-essential amino acid synthesised come from?
Where is the amino group provided from?
- Intermediates of glycolysis (C3)
- Pentose phosphate pathway (C4/C5)
- Krebs cycle (C4/C5)
- Other amino acids, transamination process or from ammonia.
Why is removal of nitrogen from AA’s essential?
What are the 2 main pathways that facilitate this removal?
- Allows skeleton of AA’s to be utilised in oxidative metabolism. Once removed, can be incorporated into other compounds or removed in urea.
- 1) Transamination + 2) Deamination
Describe the process of transamination.
What are the 2 key aminotransferase enzymes in the process and their roles?
What can plasma levels of these enzymes be used to test for?
- Aminotransferases (mostly) use a-ketoglutarate to funnel the amino group to glutamate (apart from AST which uses oxaloacetate to funnel into aspartate).
1) Alanine aminotransferase (ALT) = converts alanine to glutamate
2) Aspartate aminotransferase (AST) = converts glutamate to aspartate
- AST + ALT levels user for liver function test. Levels high in conditions causing cellular necrosis, e.g.: viral hepatitis, autoimmune liver diseases.
How does deamination work?
What does it produce and why does it need to be converted?
- Liberates amino group as free ammonia (liver + kidney)
- Ammonia very toxic and most be removed, converted to urea and excreted in urine
What are the key features of Urea?
Why is the Urea cycle important?
- High nitrogen content, non-toxic, very water soluble, chemically inert in humans, excreted in urine.
- Safely disposes of the amino group in amino acids so ammonia does not build up.
Where does the urea cycle occur?
How are the amount of the 5 enzymes involved controlled?
How are these enzymes induced/repressed?
- In the liver
- Amount of urea cycle enzymes related to the need to dispose of ammonia
- High protein diet induces enzyme levels, low protein represses levels.
NB: Cycle is inducible but NOT regulated.
How do defects in the Urea Cycle occur + what does this lead to?
What are the symptoms?
How is it managed?
- Autosomal recessive disorders leading to deficiency in one of the enzymes involved.
- Leads to hyperammonaemia + accumulation of cycle intermediates.
- Vomiting, lethargy, irritability, mental retardation, seizures + coma
- Low protein diet, replace AA’s in diet with keto acids.
Why is ammonia toxic?
What are the potential toxic effects of accumulation?
- It is readily diffusible therefore extremely toxic to the brain.
- Interference w/AA transport + PS, disruption of cerebral blood flow, alteration of BBB, interference w/TCA cycle.
