Protein and Amino Acid Metabolism Flashcards
Explain protein turnover
Protein turnover is the rate of bodily protein breakdown and re-synthesis. usually they are equal.
-The rate is dependant on the protein and whether you are in growth(faster rate) and ageing (slower rate)
in a healthy adult there is a protein turnover of 300-400g/day. 100-150g are muscle proteins and digestive enzymes
How does protein in diet affect the urea cycle
High protein diet induces enzyme levels to be higher as there will be a higher amount of ammonia present due to higher deamination activity.
Low protein diets will repress levels as there will be less ammonia present.
what are the consequences of the urea cycle being induced and not regulated.
there are 5 enzymes responsible for ammonia conversion to urea, they are induced by protein in the diet. for patients suffering from refeeding syndrome sudden increase in protein can lead to ammonia toxicity due to down regulation of urea cycle.
what is Cushings Disease
Cushings syndrome is the excessive cortisol which can lead to excessive breakdown of protein weakening the skin structure and leading to strain(stripey stretch mark looking things on abdomen)
Describe the effects of insulin GH and cortisol on protein turnover
Insulin and GH increase protein synthesis and decrease protein degradation.
Glutocortisoids(cortisol) decrease protein synthesis and increase protein degradation.
Define negative N-balance and state a situation where it would occur
When N intake is less than N loss.
starvation, malnutrition and trauma
define Positive N-balance
during periods of active growth like pregnancy, active growth and tissue repair and convalescence N intake is greater than N loss
Explain nitrogen balance
N-balance is a steady state in which the amount of N taken into the body equals the amount of N lost from the body.
>90% enters as protein and most 85% leaves as urea. 5% creatinine and 3% ammonia.
Describe how amino acids are catabolised in the body the body
Stage one: occurs in the gastrointestinal tract and is the hydrolysis of peptide bonds through peptidases and proteases to release free amino acids.
these amino acids are used for protein synthesis( stimulated by insulin and GH) and the synthesis of nitrogen containing compounds
STAGE TWO : removal of the nitrogen.
There are two main pathways: transamination(use a-ketoglutarate to funnel the amino group to glutamate) and deamination (liberates as free ammonia to be removed as urea).
The remaining carbon skeletons are them converted to acetyl-coA (ketogenic) or as oxaoacetate or a-keloglurate or fumarate of succinylcholineA)
what to glycogenic amino acid carbon skeletons deaminate to.
THINK only a king sings frank(ocean)
oxaloacetete
a-keotglutarate
succinyl~CoA
fumarate
Define Glucogenic amino acids
Amino acids that give rise to products(after amino group removal) that can be used for glucose synthesis by gluconeogenesis.
Define Ketogenic amino acids
Amino acids oproduce acetylCoA after the amino group is removed
Explain the clinical consequences of a defect in phenylamine metabolism
PKU (phenylketonuria)
defects in the first step of phenylalanine metabolism, phenylalanine hydroxylase leads to a accumulation of phenylalanine in the blood, tissue and urine as well as phenylketones in the urine.
it affects the noradrenaline, adrenaline, dopamine, melanin, thyroid hormone and protein synthesis.
the symptoms are
seizures
microcephaly (small head)
severe intellectual disability
developmental delay
hypopigmentation
can be treated with a low phenylalanine diet enriched with tyrosine ,avoiding aspartame and sweetness and high protein foods such as milk meat and eggs.
Explain the clinical relevance of measuring creatinine in blood and urine
creatinine is the breakdown product of creatine phosphate and creatine in muscles.
Creatinine urine excretion over 24h is proportional to the muscle mass and is used as an indicator of renal function ( raised plasma level and low urine levels can indicate damage to nephrons)
describe the two mechanisms of ammonia transport I the body
GLUTAMINE:
ammonia is combined with glutamate to form glutamine where it is transported in blood to the liver or kidney to be cleaved by glutaminase to reform the substrates. in the liver ammonia ia fed into the urea cycle and in the kidney it is expected directly in urine.
ALANINE: alanine aminotransferase
alanine+ a-ketoglutarate<-> pyruvate + glutamate
amine group added to glutamate via transamination(TA) to form pyruvate, which is TA’d to alanine which is transports the amine group safely in the blood to the liver, where it is broken down to pyruvate and glutamate. the ammonia in glutamate is fed into the the urea cycle for disposal where as pyruvate is used to synthesise glucose.
Describe how ammonia is metabolised in the body
Ammonia is removed from the amino group within proteins. this can happen either though transamination where the amine group is used to produce urea.
list the 9 essential amino acids
If - isoleucine
Learned - Lysine
This - Threonine
Huge - Histidine (Histamine
List -Leucine
May -Methionine
Prove-Phenyl-amine
Truly -Tryptophan (nicotinamide, serotonin and melatonin)
Valuable- Valine
list two key
aminotransferases and their functions
Alanine aminotransferases (ALT) - catalyses interconversion of alanine and a-ketoglutarate to pyruvate and glutamate
Aspartate aminotransferases.
they are measured as part of the liver function test. high levels causes cellular necrosis
effects of defects in urea cycle
All defects in any of the 5 enzymes cause hyperammonoaemia ( high blood [NH4])
Accumulation and or excretion of a particular urea cycle intermediate.
list some symptoms of defects in the urea cycle and how to manage it
Vomiting
Lethargy
Irritability
Mental retardation
Seizures
Coma
management involves having a low protein diet and replace the amino acids in diet with keto acids.
what do heel prick Guthrit tests help detect
Heel prick tests help detect sickle cell anaemia, cystic fibrosis and congenital hypothyroidism.
also inborn errors of metabolism like PKU and Homocystinuria
tell me about homocystinuria
most commonly caused by a deficiency in crystathionine-B-synthase from an autosomal recessive disorder leading to excess homocysteine
it affects connective tissue muscles and CNS and CVS. elevated levels of homocysteine are associated with cardiovascular disease.
treatment involves a low methionine diet.
avoiding milk, meat, fish, cheese and eggs.
Nuts and peanut butter also contains methionine
taking cysteine, vit b6. betaine, b12 and folate supplement.
describe and explain ammonia toxicity
Ammonia can react with a-ketoglutarate from the TCA cycle disrupting the energy supplly to the brain. it is readily diffusible and can cause alterations to blood brain barrier as well as interfering with cerebral blood flow.
it can interfere with amino acid transport and protein synthesis leading to lgreat reduction in functional proteins produced.
it is alkaline and can lead to alkalosis inside cells of the CNS and interfere with neurotransmitter synthesis.
how is ammonia detoxified
Hyperammonaemia is seen in liver disease,
glutamine is non toxic and is synthesised from ammonia and glutamate via glutamate synthetase. the glutamine is released from the cell and transported to the liver and kidney where it is hydrolysed by glutaminase releasing ammonia which is disposed of in urine(kidney) or converted to urea(liver)
why is urea an effective wy of disposing of unwanted nitrogen
it is non toxic and metabolically inert in humans. it has a high nitrogen content of 47%
the NH2 comes from the ammonia and aspartate. the ammonium comes the deamination of amino acids from gut bacteria the enter the liver through portal circulation.
aspartate is formed from the transamination of oxaloacetate.
