Flashcards in MEH - Protein/Amino Acid Metabolism Deck (50):
1
Give some examples of nitrogen containing compounds in the human body
- amino acids
- proteins
- purines/pyrimidines
- porphyrins
- creatine
- neurotransmitters
- some hormones
2
What is creatinine?
A breakdown product of creatine and creatine phosphate in the muscle
3
How is creatinine excreted?
Filtered via kidneys into urine. For men, 14-26 mg/kg per day. For women, 11-20 mg/kg per day
4
What can creatinine be used to measure?
Creatinine urine excretion over 24h is proportional to muscle mass, so it can be used to estimate it. Also often used as indicator of renal functions (raised when nephrons are damaged)
5
What does it indicate if a person has a 'positive nitrogen balance'?
Intake is larger than output, so there is an increase in total body protein. Person may be growing, pregnant or recovering from malnutrition
6
What does a negative nitrogen balance indicate?
Intake is lower than output, so there is a net loss of body protein. Causes include trauma, infection or malnutrition
7
What does it mean if the body is at nitrogen equilibrium?
No change in total body protein - normal state in adult
8
What do glucogenic amino acids undergo in the body?
Gluconeogenesis
9
What do ketogenic amino acids undergo in the body?
Ketone bodies
10
Give an example of a glucogenic amino acid
Alanine, glycine, cysteine, serine, arginine, proline, histidine, glutamine, glutamate, methionine, valine, aspartate, asparagine,
11
Give an example of ketogenic amino acids
Lysine, leucine
12
Give some examples of amino acids that are both glucogenic and ketogenic
Tryptophan, tyrosine, phenylalanine, threonine, isoleucine
13
What is the effect of insulin and growth hormone on protein synthesis/degradation?
- increases protein synthesis
- decreased protein degradation
14
What is the effect of glucocorticoids on protein synthesis?
- protein synthesis decreases
- protein degradation increases
15
Why is it important for a vegetarian diet to contain proteins from a wide variety of plant sources?
Proteins of plant origin are generally considered lower quality as most are deficient in one or more essential amino acids
16
What are the nine essential amino acids? (Mnemonic - if learned this huge list may prove truly valuable)
Isoleucine, lysine, threonine, histidine, leucine, methionine, phenylalanine, tryptophan, valine
17
Where does the body obtain the carbon atoms it requires for non-essential amino acid synthesis?
- intermediates of glycolysis
- pentose phosphate pathway
- Krebs cycle
18
Where does the body obtain the amino group for non-essential amino acid synthesis?
It is provided by other amino acids by the process of transamination or from ammonia
19
What is tyrosine used to synthesise?
Catecholamines, melanin, thyroid hormones
20
What is cysteine used to synthesise?
Hydrogen sulphide, glutathione
21
What is tryptophan used to synthesise?
Nicotinamide, serotonin, melatonin
22
What is histidine used to synthesise?
Histamine
23
What is glutamate used to synthesise?
GABA
24
What is glycine used to synthesise?
Purines, glutathione, haem, creatine
25
What is arginine used to synthesise?
Nitric oxide
26
What is serine used to synthesise?
Sphingosine
27
What is transamination?
Swapping the amine group of an amino acid with the oxygen of a keto acid
28
What are the two main aminotransferase enzymes?
Alanine aminotransferase (ALT - converts alanine to glutamate)
Aspartate aminotransferase (AST - converts glutamate to aspartate)
29
Give some examples of conditions that may cause high plasma ALT and AST levels
- viral hepatitis
- autoimmune liver diseases
- toxic injury
30
What is deamination?
The liberation of an amino group as free ammonia, which mainly occurs in the liver and kidney. The ammonia is very toxic so it is removed by conversion to urea or being excreted in the urine.
31
Why is deamination important?
Used for deamination of dietary D-amino acids, and keto acids can be used for energy
32
Which enzymes can be used to deamination amino acids?
- amino acid oxidases
- glutaminase
- glutamate dehydrogenase
33
Give some characteristics of urea
- high nitrogen content
- non-toxic
- extremely water soluble
- chemically inert in humans (bacteria can break it down though)
- performs useful osmotic role in kidney tubules
- excreted in urine via the kidneys
34
Describe the function of the urea cycle
Allows amine groups of amino acids in the body to be safely disposed of as urea. Input of glutamate and aspartate, ammonia goes through cycle and ends up as urea.
35
Where does the urea cycle occur?
In the liver
36
How many enzymes are involved in the urea cycle?
5 - a high protein diet increases the amount of these, and a low protein diet decreases the amount of them
37
What is refeeding syndrome?
Occurs when nutritional support given to severely malnourished patients. The urea cycle has been down-regulated due to lack of food, so they suffer from ammonia toxicity.
38
What can cause a defect in the urea cycle?
Autosomal recessive genetic disorders caused by deficiency in one of the enzymes in the urea cycle can cause a partial loss of enzyme function and lead to hyperammonaaemia and accumulation/excretion of urea cycle intermediates
39
What are the symptoms of defects in the urea cycle?
- vomiting
- lethargy
- irritability
- intellectual disability
- seizures
- coma
40
How are urea cycle defects managed?
Low protein diet and replace amino acids in diet with keto acids
41
What is the normal blood ammonia level?
25-40 micromoles/L
42
Give some potentially toxic effects of high ammonia levels in the body?
- interference with amino acid transport and protein synthesis
- disruption of cerebral blood flow
- pH effects (alkaline)
- alteration of blood-brain barrier
- interference with TCA cycle
- interference with metabolism of excitatory amino acid neurotransmitters
43
What are the two methods for removing ammonia from the body?
- combined with glutamate to form GLUTAMINE
- transported in blood to liver or kidneys, cleaved by glutaminase to reform glutamate and ammonia
- in liver, ammonia fed into urea cycle, in kidney it is excreted directly
OR
- combined with pyruvate to form ALANINE
- transported to liver, converted back to pyruvate by transamination
- amino group fed via glutamate into urea cycle, pyruvate used to synthesise glucose
44
What is the heel prick test used to detect in babies?
Sickle cell disease, cystic fibrosis, congenital hypothyroidism, inborn errors of metabolism
45
What is phenylketonuria?
Autosomal recessive disorder of phenylalanine hydroxylase. Leads to accumulation of phenylalanine in tissue, plasma and urine and phenylketones in the urine.
46
How is phenylketonuria treated?
- strictly controlled low phenylalanine diet
- avoid artificial sweeteners
- avoid high protein foods such as meat, milk and eggs
47
Which pathways are affected in phenylketonuria?
Phenylalanine cannot be converted to tyrosine, leading to problems with noradrenaline/adrenaline formation, dopamine, melanin, thyroid hormone and protein synthesis
48
Give some symptoms of phenylketonuria
- severe intellectual disability
- developmental delay
- microcephaly
- seizures
- hypopigmentation
49
What are 'homocystinurias'?
Autosomal recessive defect in cystathionine beta-synthase causes a problem breaking down methionine, leading to excess homocysteine being excreted in urine. Affects connective tissues, muscles, CNS and CVS
50