Protein Metabolism and nitrogen balance Flashcards
Common structure of amino acids and how many are there
-COOH and -NH2 groups
20 amino acids in the body
10 are derived from the diet 10 are non-essential i.e. made by the body
where are proteins absorbed?
- absorbed as amino acids in the ileum (small quantities at a time as digestion very long) via active transport
- also absorbed in proximal tubules but can be excreted in the urine if above threshold
How are proteins metabolised?
Protein (digested) > Amino Acid (Deaminated) > Glucose, fatty acid or ketone body + Ammonia (urea cycle) > Urea
How are Amino acids stored and released from storage?
- Can’t be stored as free AA’s so combine to form peptides or intracellular proteins
- Lysosomal enzymes break down intracellular proteins to release AA’s
- Stored in the liver primarily but also kidneys and intestinal mucosa
- Cells have protein storage capacity, excess used immediately for energy or converted to fat/glycogen
What are the types of plasma protein?
Albumin - Generates colloid pressure to prevent plasma loss from capillaries
Globulins - antibodies for immunity
Transferrin - carriage of ferrous ions
Fibrinogen - mediates clot formation
How are proteins metabolised in the liver?
Transamination: synthesise of non-essential amino acids
deamination: degradation and energy generation (removal of ammonia)
oxidation: generates energy by ketogenesis or gluconeogenesis (addition of oxygen)
Excretion: via the urea cycle
What is transamination and what does it require?
- When an amino group is transferred from an amino acid to an alpha-keto acid
- Requires aminotransferase/transaminase, Vitamin B6 is also necessary for the function of aminotransferase
- A different amino acid and alpha-keto acid form
What is deamination and when does it occur?
- Deamination occurs in the liver when there are excess amino acids
- Amino group is removed from the AA’s using aminotransferase (not transferred to anything like in transamination)
- leaves the carbon skeleton of the amino acid
- carbon skeleton broken down into Glucose, Acetyl CoA and Ketone bodies form as well as CO2, O2 and ammonia (ammonia from amino group)
- if not oxidised in TCA amino group can be transferred or released as ammonium in urea cycle
How can deaminated amino acids be converted to energy (oxidation)?
1) Gluconeogenesis - ketone can enter TCA cycle
2) Ketogenesis - Acetyl CoA production which can enter TCA cycle (ketones generated)
What are the waste products of deamination and how are they rid off?
- Ammonia - highly toxic so is rapidly ionised to ammonium
- Ammonium is converted to urea and excreted in urine
Describe the Urea cycle?
Ornithine (+ Carbamoyl phosphate, formed by CO2+ NH4+) >
Citrulline (+ Aspartate) >
Argininosuccinate (byproduct fumerate released) >
Arginine (+H2O) (byproduct Urea released) >
Ornithine…
What are the available energy stores and in a state of starvation how are they used?
Carbohydrates - very little storage but glycogen which is stored is broken down
Protein - initially all readily accessible stores are depleted using gluconeogenesis but rest are mainly utilised as the last option
fat - primary energy source, used until fully depleted
Which hormones regulate protein metabolism?
Growth Hormone - Promotes synthesis of cellular proteins, increases AA membrane transport
Insulin - Promotes cellular uptake of AA’s, inhibits protein catabolism and decreases gluconeogenesis
Both increase RNA transcription/translation
- lack of insulin > more plasma AA’s > more gluconeogenesis > more muscle wastage
How does testosterone regulate protein metabolism?
transient muscle growth - induces contractile proteins
How does oestrogen regulate protein metabolism?
Muscle growth but minor
How does thyroxine regulate protein metabolism?
increase cell metabolism - if carbs/fat low then protein degradation, if carbs/fat high then protein synthesised
How do glucocorticoids regulate protein metabolism?
increase protein breakdown, increase circulating AA’s and plasma proteins so more gluconeogenesis
Describe Citrullinemia?
Arginosuccinate synthase deficiency so ammonia accumulates
Describe Tyrosinemia?
deficiency in tyrosine aminotransferase resulting in liver disease
Describe Phenylketonuria?
defect in PAH gene so lack of phenylalanine hydroxylase causing damage to CNS
Which food do you get nitrogen from and in what forms is it excreted?
Food: Meat, fish, milk, eggs, cereal, legumes
excreted: primarily Urea but also creatinine, uric acid and ammonia
How much protein do you need to balance losses
20-30 g/day but recommend 50g
How is nitrogen balance measured?
Dietary protein (intake) - urinary nitrogen (output) taking into account dynamic protein turnover in the body (estimated at 3-4 g/kg/day)
When might you have a Positive or negative nitrogen balance?
+ When increased protein demand e.g. pregnacny
- Starvation (protein intake insufficient)
- Cachexia (loss of body mass which can’t be reversed nutritionally e.g. in cancer
- also get negative balance when negative energy balance as protein used for energy
What are the products of deamination?
- Ammonia
- H2O + CO2
- Glucose
- Acetyl CoA
- Ketone bodies
