Protein And AA Metabolism Flashcards
What are major nitrogen containing compounds
Major Nitrogen containing compounds: • Amino acids • Proteins • Purines + Pyrimidines (DNA / RNA) Smaller amounts of others – e.g. • Porphyrins (haem) • Creatine phosphate • Neurotransmitters (e.g. dopamine) • Some hormones (e.g. adrenaline)
What is creatinine?
- Breakdown product of creatine & creatine phosphate in muscle
- Usually produced at constant rate depending on muscle mass (unless muscle is wasting)
- Filtered via kidneys into urine
- Creatinine urine excretion over 24h proportional to muscle mass
- Provides estimate of muscle mass
- Also commonly used as indicator of renal function (raised level on damage to nephrons)
What happens when N intake = output
No change in total body protein. Normal state in adult.
What happens when N intake > output
Increase in total body protein. Normal state in growth & pregnancy or in adult recovering from malnutrition.
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What happens when N intake < output
Net loss of body protein. Never normal. Causes include trauma, infection, or malnutrition.
Describe protein turnover
See slide
Give an example of a glucogenic, ketogeinc and both AA
Gluco: ala, gly, cys, ser, asp, asg, arg, pro, his, glu
Keto: lys, leu
Both: thr, try, tyr, phe,
One of each
When does mobilisation of protein reserves occur?
- Occurs during extreme stress (starvation)
* Under hormonal control
What effect do insulin/growth hormones and glucocorticoids have on protein synthesis and degradaion?
Insulin and growth hormone: increase protein synthesis, decrease protein degradation
Glucocorticoids: decease protein synthesis, increase protein degradation
What is Cushing syndrome
Excessive breakdown of protein can occur in Cushing’s syndrome (excess cortisol). Weakens skin structure leading to striae formation.
What are the 9 essential amino acids
Isoleucine, lysis, threonine, histidine, leucine, methionine, phenylalanine, tryptophan, valine
If learned this huge list may prove truly valuable
Cannot be made by the body so must be obtained form food
What are the conditionally esential amino acids
- Certain amino acids are Conditionally essential
- Children & Pregnant women = high rate of protein synthesis. Also require some arginine, tyrosine & cysteine in diet
What is the difference between plant and animal protein
- Protein of animal origin considered “High quality” (Contain all essential amino acids)
- Proteins of plant origin generally considered “lower quality” since most are deficient in one or more essential amino acids.
- Therefore essential that vegetarian diet obtains protein from a wide variety of plant sources
Where do non essential amino acids come from?
• In addition to dietary intake, body can synthesise
some amino acids it requires (the non-essential amino acids)
• Carbon atoms for non-essential amino acid synthesis come from:
• Intermediates of glycolysis (C3)
• Pentose phosphate pathway (C4 & C5)
• Krebs cycle (C4 & C5)
• Amino group provided by other amino acids by the process of transamination or from ammonia.
What are amino acids required to synthesise?
In addition to protein synthesis (requires all 20 amino acids) amino acids also required for synthesis of other important compounds (requires specific amino acids).
Tyrosine
• Catecholamines
• Melanin
• Thyroid hormones
Histidine
• Histamine
Arginine
• Nitric oxide
Cysteine
• Hydrogen sulphide (signalling molecule)
• Glutathione
Glutamate
• GABA
Serine
• Sphingosine
Tryptophan
• Nicotinamide
• Serotonin (5HT)
• Melatonin
Glycine • Purines • Glutathione • Haem • Creatine
Describe removal of nitrogen from amino acids
• Removal of amino group is essential to allow carbon
skeleton of amino acids to be utilised in oxidative
metabolism
• Once removed nitrogen can be incorporated into other compounds or excreted from body as urea
• Two main pathways facilitate removal of nitrogen from amino acids
Transamination and deamination
What are the 2 main aminotransferase enzymes?
Alanine aminotransferase ( A LT ) Converts alanine to glutamate Aspartate aminotransferase (AST) Converts glutamate to aspartate
Plasma ALT and AST levels measured routinely as part of liver function test Levels particularly high in conditions that cause extensive cellular necrosis such as:
• Viral hepatitis
• Autoimmune Liver Diseases
• Toxic injury
Death cap mushrooms cause acute liver failure if ingested as plasma ATl levels up top 20x normal
What is deamination?
Liberates amino group as free ammonia
• Mainly occurs in liver & kidney
• Keto acids can be utilised for energy
• Also important in deamination of dietary D-amino acids (found in plants and microorganisms) (need it in the L form as enzymes cant deal with D form)
• Ammonia (and ammonium ions) very toxic and must be removed. Ultimately converted to urea or excreted directly in urine
At physiological pH, ammonia (NH3) is rapidly converted to ammonium ion (NH4+)
Which enzymes can deamination amino acids `
AA oxidases
Glutaminase
Glutamate dehydrogenase
What is urea
NH2CONH2
- High nitrogen content
- Non-toxic
- Extremely water soluble
- Chemically inert in humans (bacteria can break it down to release NH
- Most urea is excreted in urine via the kidneys
- Also performs useful osmotic role in kidney tubules
What is the urea cycle?
Ornithine cycle
• Occurs in liver and involves 5 enzymes
• Amount of urea cycle enzymes normally related to need to dispose of ammonia
• High protein diet induces enzyme levels
• Low protein diet or starvation represses levels
• Cycle is inducible but not regulated
What is refeeding syndrome
- Can occur when nutritional support given to severely malnourished patients
- Ammonia toxicity significant factor (urea cycle down regulated)
- Re-feed @ 5 to 10 kcal/kg/day. Raise gradually to full needs within a week
Enzymes in urea cycle not sufficiency to deal with amie groups in big meal - leads to ammonia toxicity
Describe defects in the urea cycle
• Autosomal recessive genetic disorders caused by deficiency of one of enzymes in the urea cycle
• Occur ~1 in 30,000 live births
• Mutations cause a partial loss of enzyme function
• Leads to:
- hyperammonaemia
- accumulation/excretion of urea cycle intermediates
Clinical picture (NH3 toxicity)
• Severity depends on:
- nature of defect
- amount of protein eaten
• Severe urea cycle disorders show symptoms within 1 day after birth. If untreated, child will die.
• Mild urea cycle enzyme deficiencies may not show symptoms until early childhood
Symptoms • Vomiting • Lethargy • Irritability • Mental retardation • Seizures • Coma
Management:
• Low protein diet
• Replace amino acids in diet with keto acids
Why does ammonia concentration in the blood need to be kept low?
- Readily diffusible and extremely toxic to brain
- Blood level needs to be kept low (25-40 µmol/L)
- Several potential toxic effects:
- Interference with amino acid transport and protein synthesis
- Disruption of cerebral blood flow
- pH effects (alkaline)
- Interference with metabolism of excitatory amino acid neurotransmitters (e.g. glutamate and aspartate)
- Alteration of the blood–brain barrier
- Interference with TCA cycle (reacts with α-ketoglutarate to form glutamate)
