Protein and Amino Acid Metabolism Flashcards
Where does stage 1 of catabolism of proteins occur and what enzymes are involved
Occurs in the GI tract
Proteases and peptidases break protein down into amino acids which are absorbed
What molecules stimulate uptake of protein into cells and what molecule stimulates breakdown of proteins
Uptake - insulin and growth hormone
Breakdown - cortisol
What are the types of amino acids
Ketogenic
Glucogenic
Ketogenic and Glucogenic
How are amino acids catabolised
Amino group removed and converted to urea
Remaining C-skeleton converted to one or more of: pyruvate, oxaloacetate, fumarate, alpha-ketoglutarate, succinate CoA, acetyl CoA, acetoacetyl CoA
Why are amino acids described as Ketogenic and what can they be used to synthesise
They produce acetyl CoA when catabolised (or acetoacetyl CoA)
Acetyl CoA then used to make ketone bodies or fatty acids
Why are amino acids described as Glucogenic and what can they be used to synthesise
They produce other products (not acetyl CoA) when catabolised
Synthesise glucose or glycogen
What are the terms used to describe the intake of nitrogen against loss of nitrogen
N-balance - where intake equals loss
Positive N-balance - intake is greater than loss
Negative N-balance - intake less than loss
When would a person have positive N-balance and when would they have negative N-balance
Postive N-balance - active growth, pregnancy, tissue repair, convalescence
Negative N-balance - starvation, malnutrition, trauma
What are the essential amino acids
Isoleucine
Lysine
Threonine
Histidine
Leucine
Methionine
Phenylalanine
Tryptophan
Valine
Which amino acids are conditionally essential and under what circumstances are they essential
Arginine - during periods of active growth (body can synthesise small quantity)
Tyrosine - if diet low in phenylalanine (synthesised from it)
Cysteine - if diet low in methionine (synthesised from it)
Why is a regular and adequate supply of protein needed in the diet
To replace the amino acids that are not reutilised after protein breakdown
What are the two signalling molecules synthesised from amino acids
Nitric oxide from L-arginine
Hydrogen sulphide from L-cysteine
What are the three features of amino acid breakdown
C-atoms converted to intermediates of carbohydrate and lipid metabolism
Start with removal of NH2 group by transamination of deamination)
N-atoms usually converted to urea
What are the two ketogenic only amino acids
Leucine
Lysine
Which amino acids are both glucogenic and ketogenic
Isoleucine
Tyrosine
Phenylalanine
Tryptophan
Which enzymes are involved in transamination and what stimulates their synthesis
Aminotransferases
Cortisol
Which molecules can be used in transamination as keto acid 2 and what are they converted to
Alpha-ketoglutarate - converted to glutamate
Oxaloacetate - converted to aspartate
Which two tranaminases are clinically important and why
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Important as used when assessing liver function - measured in serum
What is deamination and which groups of enzyme are involved
Removal of the NH2-group as a free NH3
L and D-amino acid oxidases - convert amino acids to keto acids and NH3
What are the importance of D-amino acid oxidases
Convert D-amino acids into keto acids as D-amino acids cannot be used for protein synthesis as they are the wrong optic isomer
What does glutaminase do
Converts glutamine to glutamate and NH3
Why is glutamate dehydrogenase important
Involved in disposal of amino acids and synthesis of non-essential amino acids
Produces alpha-ketoglutarate from glutamate
When do disorders of amino acid metabolism usually have a clinical consequence
When affected enzyme is involved in amino acid breakdown
This is because it allows the amino acid to accumulate and the AA may be toxic itself and/or be metabolised to toxic products
Restrict amount of amino acid in diet
What is phenylketonuria/PKU
Inherited metabolic disorder where urine contains large amounts of phenylketones produced from phenylalanine
Usually there is defect in phenylalanine hydroxylase and as a result phenylalanine accumulates in tissues and blood
Phenylalanine is metabolised by other pathways to produce other products, including phenylpyruvate
What are the consequence if PKU is left untreated
Inhibition of brain development as phenylpyruvate inhibits pyruvate uptake into mitochondria, interfering with energy metabolism in the brain
Associated with seizures, microcephaly
How do you test for PKU
Heel prick test shortly after birth
What is homocystinuria
Inherited autosomal recessive defect in methionine metabolism, in which Type 1 is cauesd by deficiency in cystathionine beta-synthase (CBS) enzyme
CBS normally converts homocysteine to cystathionine which is then converted to cysteine
Homocysteine levels rise and some can be converted to methionine
How is homocystinuria usually detected
Elevated levels of homocysteine and methionine in the plasma
Homocytine in the urine
What can homocystinuria cause
Disorders of connective tissue, muscle, CNS, cardiovascular system
Due to chronic elevated plasma levels of homocysteine
What is the mechanism behind ammonia’s toxicity
Reacts with alpha-ketoglutarate to form glutamate in mitochondria via glutamate dehydrogenase
This removes alpha-ketoglutarate from TCA cycle, slowing it
This disrupts energy supply to brain cells
May affect pH inside cells of CNS and may interfere with neurotransmitter synthesis and release
What are the clinical effects of hyperammonaemia
Blurred vision
Tremors
Slurred speech
Coma
Death
Interference with amino acid transport and protein synthesis
Disruption of cerebral blood flow
Alkaline effects
Interference with metabolism of excitatory amino acid neurotransmitters
Alteration of blood brain barrier
Interference with TCA cycle
How can ammonia be detoxified
Used in synthesis of N-compounds - glutamate
Conversion to urea and excreted
Ammonia can be excreted directly in urine
Describe glutamine synthesis
Synthesised from ammonia and glutamate via glutamine synthetase
How is glutamine synthesis used to combat ammonia toxicity
Glutamine is synthesised using ammonia in cell and is then released where it is transported to the liver and kidney
Glutamine is then hydrolysed by glutaminase releasing ammonia which can be excreted in urine or converted to urea
How is alanine used in ammonia detoxification
Pyruvate transaminated in tissue by glutamate to produce alanine
Alanine travels in blood to liver
In liver amine group transferred to glutamate and pyruvate produced from reaction which can travel back to tissues to be used again
How is urea synthesis regulated and what condition is associated with giving too much protein quickly to malnourished patients
Enzymes of the cycle are inducible with high protein diet inducing the enzyme and vice versa
Refeeding syndrome is caused by giving too much protein too soon to malnourished as the excess amino acids are degraded leading to hyperammonaemia
Describe the inherited diseases of the urea cycle
A set of autosomal recessive diseases affecting one of the enzymes in the cycle
Can only be partial loss of the enzyme as full loss is fatal
What are the symptoms of inherited diseases of the urea cycle
Vomiting
Lethargy
Irritability
Mental retardation
Seizures
Coma
What is the treatment for diseases of the urea cycle
Low protein diets
Diets where keto acids of essential amino acids are used to replace the amino acids themselves
When might hyperammonaemia develop as a secondary consequence
Due to liver disease like cirrhosis
Liver’s ability to remove NH3 from portal blood is impaired
What happens to urea in the body
Most is filtered and excreted in the urine
A small amount crosses the intestinal wall, entering intesine where bacteria then break it down releasing ammonia that can be reabsorbed
