1.2 - Protein And Amino Acid Metabolism Flashcards
1
Q
Name 3 major nitrogen containing compounds
A
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)
2
Q
What is the function of creating and creating phosphate?
A
To provide short term energy supply in muscle
3
Q
How is creatinine formed?
A
Formed as a breakdown product of creatinine and creating phosphate
4
Q
Why is it useful to measure creatinine levels in urine?
A
Creatinine content of urine over 24 hours is proportional to muscle mass. Therefore by measuring we can estimate of muscle mass. Usually released at a constant rate. During muscle wastage, rate of creatinine production would increase. Commonly used as an indicator of renal function, raised creatinine in urine on damage to nephrons as kidneys usually accurately expel creatinine
5
Q
What is a nitrogen balance?
A
A comparison of the nitrogen consumed in our diet through protein vs the nitrogen lost from our body through loss of skin/hair/nails and nitrogen containing waste products in faeces and urine.
6
Q
What is nitrogen equilibrium?
A
Nitrogen Intake = nitrogen output
No change in total body protein. Normal state in adult
7
Q
What is a positive nitrogen balance?
A
Nitrogen Intake > nitrogen output
Increase in total body protein. Normal state in growth & pregnancy or in adult recovering from malnutrition.
8
Q
What is a negative nitrogen balance?
A
Intake < output
Net loss of body protein. Never normal. Causes include trauma, infection, or malnutrition.
9
Q
How much nitrogen is usually consumed each day?
A
16g
10
Q
What is the first stage in the catabolism of proteins?
A
Enzymes (proteases and peptidases) hydrolyse peptide bonds to release free amino acids in the gastrointestinal tract. Amino acids are then absorbed into the circulation.
Excess amino acids are broken down in stage 2 of protein catabolism.
11
Q
What is the largest food store in an average man?
A
Triacylglycerol (15 kg)
12
Q
When is muscle protein used as a fuel?
A
During prolonged starvation
13
Q
Why are purple striae seen in Cushing’s syndrome?
A
There is excessive breakdown of protein due to excess cortisol. This weakens skin structure and leads to striae formation.
14
Q
How are free circulating amino acids used?
A
For synthesis of protein and other nitrogen containing compounds (purines, creative, haem).
15
Q
What tissues uptake amino acids?
A
Skeletal muscle
Adipose tissue
Liver
16
Q
What regulates protein synthesis?
A
Insulin
Growth hormones
17
Q
What hormone stimulates proteolysis?
A
Cortisol
18
Q
Describe the second stage of protein catabolism after amino acids have been freed.
A
Amino group is removed and converted to urea (CO(NH2)2) which is excreted in urine.
Reminding carbon skeletons are converted to acetyl-CoA, pyruvate, oxaloacetate, fumurate and other products that can be used for glycolysis
19
Q
What is the difference between a ketogenic and glucogenic?
A
Ketogenic amino acids (leucine and lysine) produce acetyl-CoA which is used to synthesise ketone bodies
Glucogenic amino acids give rise to other products such as Pyruvate and oxaloacetate which can be used for gluconeogenesis.
Some amino acids can be both ketogenic and gluconeogenic
20
Q
How does nitrogen leave the body?
A
In hair/nails/skin
In urea, ammonia, uric acid and creatinine in urine.
21
Q
How are proteins generated when required?
A
Synthesised from free amino acids, protein is not stored.
22
Q
What factors influence the rate of protein turnover?
A
The type of protein
Age
Periods of growth
23
Q
Where does the second stage of protein catabolism occur?
A
In the liver.
24
Q
Where do carbon atoms for non-essential amino acid synthesis come from?
A
Intermediates of glycolysis
Pentose phosphate pathway
Kreps cycle
25
How many amino acids are in the human body?
20
26
How do amino acid structures vary?
According to the side chain R
27
What is the amino acid pool?
Total free amount of amino acids in the body and is 100g in the average male.
28
What is normal fasting concentration of amino acids in the blood?
3mm/L
29
What are non-essential amino acids?
Amino acids that can be synthesised by the body, with carbon atoms from intermediates of metabolic pathways and amino group from othe amino acids by the process of transamination or from ammonia.
30
What happens to excess amino acids?
Enter stage 2 catabolism to be converted into intermediates of carbohydrate or lipid metabolism or oxidised to produce energy as cannot be stored or excreted.
31
What are essential amino acids?
Amino acids that cannot be synthesised by the body.
32
Name the 9 essential amino acids
```
Isolyeucine
Lysine
Threonine
Histidine
Leucine
Methionine
Phenylalanine
Tryptophan
Valine
```
If learned, this huge list may prove truly valueable
33
Name 3 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)
34
What is the function of creating and creating phosphate?
To provide short term energy supply in muscle
35
How is creatinine formed?
Formed as a breakdown product of creatinine and creating phosphate
36
Why is it useful to measure creatinine levels in urine?
Creatinine content of urine over 24 hours is proportional to muscle mass. Therefore by measuring we can estimate of muscle mass. Usually released at a constant rate. During muscle wastage, rate of creatinine production would increase. Commonly used as an indicator of renal function, raised creatinine in urine on damage to nephrons as kidneys usually accurately expel creatinine
37
What is a nitrogen balance?
A comparison of the nitrogen consumed in our diet through protein vs the nitrogen lost from our body through loss of skin/hair/nails and nitrogen containing waste products in faeces and urine.
38
What is nitrogen equilibrium?
Nitrogen Intake = nitrogen output
| No change in total body protein. Normal state in adult
39
What is a positive nitrogen balance?
Nitrogen Intake > nitrogen output
| Increase in total body protein. Normal state in growth & pregnancy or in adult recovering from malnutrition.
40
What is a negative nitrogen balance?
Intake < output
| Net loss of body protein. Never normal. Causes include trauma, infection, or malnutrition.
41
How much nitrogen is usually consumed each day?
16g
42
What is the first stage in the catabolism of proteins?
Enzymes (proteases and peptidases) hydrolyse peptide bonds to release free amino acids in the gastrointestinal tract. Amino acids are then absorbed into the circulation.
Excess amino acids are broken down in stage 2 of protein catabolism.
43
What is the largest food store in an average man?
Triacylglycerol (15 kg)
44
When is muscle protein used as a fuel?
During prolonged starvation
45
Why are purple striae seen in Cushing’s syndrome?
There is excessive breakdown of protein due to excess cortisol. This weakens skin structure and leads to striae formation.
46
How are free circulating amino acids used?
For synthesis of protein and other nitrogen containing compounds (purines, creative, haem).
47
What tissues uptake amino acids?
Skeletal muscle
Adipose tissue
Liver
48
What regulates protein synthesis?
Insulin
| Growth hormones
49
What hormone stimulates proteolysis?
Cortisol
50
Describe the second stage of protein catabolism after amino acids have been freed.
Amino group is removed and converted to urea (CO(NH2)2) which is excreted in urine.
Reminding carbon skeletons are converted to acetyl-CoA, pyruvate, oxaloacetate, fumurate and other products that can be used for glycolysis
51
What is the difference between a ketogenic and glucogenic?
Ketogenic amino acids (leucine and lysine) produce acetyl-CoA which is used to synthesise ketone bodies
Glucogenic amino acids give rise to other products such as Pyruvate and oxaloacetate which can be used for gluconeogenesis.
Some amino acids can be both ketogenic and gluconeogenic
52
How does nitrogen leave the body?
In hair/nails/skin
In urea, ammonia, uric acid and creatinine in urine.
53
How are proteins generated when required?
Synthesised from free amino acids, protein is not stored.
54
What factors influence the rate of protein turnover?
The type of protein
Age
Periods of growth
55
Where does the second stage of protein catabolism occur?
In the liver.
56
Where do carbon atoms for non-essential amino acid synthesis come from?
Intermediates of glycolysis
Pentose phosphate pathway
Kreps cycle
57
How many amino acids are in the human body?
20
58
How do amino acid structures vary?
According to the side chain R
59
What is the amino acid pool?
Total free amount of amino acids in the body and is 100g in the average male.
60
What is normal fasting concentration of amino acids in the blood?
3mm/L
61
What are non-essential amino acids?
Amino acids that can be synthesised by the body, with carbon atoms from intermediates of metabolic pathways and amino group from othe amino acids by the process of transamination or from ammonia.
62
What happens to excess amino acids?
Enter stage 2 catabolism to be converted into intermediates of carbohydrate or lipid metabolism or oxidised to produce energy as cannot be stored or excreted.
63
What are essential amino acids?
Amino acids that cannot be synthesised by the body.
64
Name the 9 essential amino acids
```
Isolyeucine
Lysine
Threonine
Histidine
Leucine
Methionine
Phenylalanine
Tryptophan
Valine
```
If learned, this huge list may prove truly valueable
65
What are conditionally essential amino acids?
Arginine tyrosine cysteine
Only essential during high rates of protein synthesis (children + pregnant women)
66
Why are vegan diets prone to essential amino acid deficiencies?
Protein of plant origin maybe deficient in one or more essential amino acids.
67
How are amino groups removed from amino acids when they are broken down?
By transamination or deamination.
68
What is transamination?
A mechanism for removal of -NH2 from amino acids. Aminotransferases swap R groups of amino acids. Most aminotransferases use alpha ketoglurate to funnel the amino group to form glutamate.
69
What molecules does aspartate aminotransferases use to transfer amino groups to ?
Oxaloacetate is used to gain the amino group to form aspartate.
70
What coenzyme do all aminotransferases require?
Pyridoxal phosphate (derivate of vitamin B6)
71
What hormone stimulate aminotransferase synthesis in the liver?
Cortisol
72
Why are some aminotransferases measured in serum?
Alanine aminotransferases and aspartate aminotransferase are both measured in serum to asses liver function levels. Conditions that cause cellular necrosis ( viral hepatitis, autoimmune liver diseases and toxic injury) raise levels of aspartate aminotransferase and alanine aminotransferase.
73
What is deamination?
A mechanism of liberating the amino group from amino acids as free ammonia. D amino acid oxidases are low specifity enzymes that convert amino acids into keto acids and ammonia.
74
Where does deamination occur?
In the liver and kidneys
75
What is glutaminase?
A high specificity enzyme involved in the deamination of glutamine to glutamate. Involved in non-essential amino acid synthesis. Glutamate is a keto acid that can be utilised for energy.
76
Why is ammonia converted to urea?
Ammonia is toxic whilst urea is not. Urea is also water soluble so can be easily excreted in urine. Urea is chemically inert.
77
What are the products of amino acid catabolism used for?
The amino group can be used for synthesis of non-essential amino acids as well as other N-continuing compounds or ammonia/urea.
The carbon skeleton can be utilised for energy in oxidative metabolism
78
What is the function of alanine aminotransferase?
Converts alanine to glutamate
79
What is the function of aspartate aminotransferase
| ?
Converts glutamate to aspartate
80
What are death cap mushrooms?
Mushrooms that cause acute liver failure if ingested. Raise plasma alanine aminotransferase levels up to 20 times normal levels.
81
How is the concentration of dietary ammonia kept low?
Rapidly converted to ammonium ion NH4. Ammonia and ammonia ions are absorbed in the gut so concentration in peripheral blood is kept low.
82
Where does the urea cycle occur?
In the liver
83
How many enzymes are involved in the urea cycle?
5
84
How are enzymes in the urea cycle controlled?
Enzymes are induced by high protein diet and suppressed by low protein diet or starvation. Cannot be regulated by feedback inhibition as the final product urea is disposed of in urine.
85
What is refeeding syndrome?
Can occur when nutritional support given
to severely malnourished patients.
- Starving individuals have very low activity of the enzymes of the urea cycle
- rapid refeeding leads to ammonia toxicity (hyperammonaemia as the excess amino acids are degraded).
- More significantly, the rapid re-feeding of energy rich foods in starved or inadequately nourished patients will rapidly increase blood sugar and insulin, resulting in glycogen, fat and protein synthesis. These processes will utilise magnesium, phosphate and potassium from body stores that are already depleted and therefore result in electrolyte abnormalities such as hypophosphataemia resulting in a condition known as refeeding syndrome.
86
What patients are at risk of developing refeeding syndrome?
```
Low BMI (<16)
Unintentional weight loss of >15% in 3-6 months
10 days or more with little to no nutritional intake
```
87
What causes defects in the urea cycle?
Autosomal recessive genetic disorders caused by deficiency of one of the enzymes in the urea cycle. Mutations cause a partial loss of enzyme function
88
What clinical problems may result in a patient with a defect in the urea cycle?
Hyperammonaemia
| Accumulation/excretion of urea cycle intermediates
89
What are the symptoms of a patient with a defect in their urea cycle?
• Vomiting • Lethargy • Irritability • Mental retardation • Seizures • Coma
90
What affects the severity of the presenting symptoms of a patient with defects in their urea cycle?
Nature of the defect
| Amount of protein eaten
91
How can we manage urea cycle deficiencies?
Low protein diet
Replace amino acids in diet with keto acids (as keto acids are converted to amino acids using some of the NH4+ ammonium ion
92
What conditions may cause hyperammonaemia as a secondary consequence?
Defect in the urea cycle (autosomal recessive genetic disorder caused by deficiency in one of the enzyme of the urea cycle)
Liver diseases such as liver cirrhosis ( affect the livers ability to remove ammonia from the portal blood system)
93
Why is ammonia toxic to the CNS?
Readily diffusible and easily crosses the blood brain barrier and extremely toxic to brain. Ammonia removes keto acids and removes enzymes (alpha ketoglutarate) from the TCA cycle, slowing and disrupting energy supply to brain cells. Also affects the pH inside the cells of the CNS and interfere with neurotransmitter synthesis and release.
94
What are the potential toxic effects of ammonia to cells of the body?
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)
95
What two mechanisms are utilised for the safe transport of amino acid nitrogen from tissues to the liver for disposal?
1. Glutamine - ammonia is combined with glutamate to form glutamine which can be transported in the blood. Glutamine synthetase stimulates this reaction. Opposite to the glutaminase.
2. Alanine
Amine groups transferred to glutamate by transamination of amino acid and alpha ketoglutarate. Pyruvate then transaminated by glutamate to form alanine. Alanine transported in blood to liver.
96
Glutamine and alanine carry amino groups to the liver. What happens when they enter the liver?
1. Glutamine transported in blood to liver or
kidneys where it is cleaved by glutaminase to
reform glutamate and ammonia. In liver ammonia fed into urea cycle. In kidney excreted directly in urine
2. Alanine transported in blood to liver where it is converted back to pyruvate by transamination. Amino group fed via glutamate into urea cycle for disposal as urea whereas pyruvate is used to synthesise glucose which can be fed back to tissues
97
If left untreated, what impairment occurs in patients with problems with amino acid metabolism?
Intellectual impairment.
98
How do we scan for protein metabolism enzyme deficiency?
Heel prick test on new borns.
99
Give some examples of inborn errors of protein metabolism
```
Phenylketonuria (PKU)
Maple syrup urine disease
Isovaleric acidaemia (IVA)
Glutaric aciduria
Homocystinuria
```
100
What is phenylketonuria?
Most common inborn error of amino acid
| metabolism. Deficiency in phenylalanine hydroxylase. Autosomal recessive. Affected gene is on chromosome 12
101
What occurs in patients with phenylketonuria?
Accumulation of
phenylalanine in tissue,
plasma & urine. Phenylketones made from phenylalanine are present in urine, giving urine a musty smell.
102
How is phenylketonuria treated?
Strictly controlled low
phenylalanine diet
enriched with tyrosine. Avoid artificial sweeteners
(contain phenylalanine). Avoid high protein foods such
as meat, milk, and eggs.
103
Why are patients with phenylketonuria deficient in tyrosine?
Defect in phenylalanine hydroxylase which functions by catalysing phenylalanine to from tyrosine. As phenylalanine hydroxylase is deficient, tyrosine cannot be synthesised in this way.
104
What pathways are affected by a deficiency in tyrosine?
```
Noradrenaline
Adrenaline
Dopamine
Melanin
Thyroid hormone
Protein synthesis
```
105
What are symptoms of phenylketonuria?
Severe intellectual disability
Developmental delay Microcephaly (small head)
Seizures
Hypopigmentation
Can be avoided with early intervention
106
How does PKU affect brain development?
Deficiency in phenylalanine hydroxylase results in high levels of phenylalanine which is a large neutral amino acid (LNAA). This competes for transport across the blood brain barrier via Large Neutral Amino Acid Transporter. (LNAAT). Excess phenylalanine saturates the transporter and levels of other LNAA in the brain decreases. Protein and neurotransmitter synthesis is reduced and Brian development is affected.
107
What is homocystinuria?
Problem breaking down methionine. Excess homocystine (oxidised form of homocysteine) excreted in urine. Autosomal recessive disorders. Incidence ~1 in 344,000. Defect in cystathionine β-synthase most common. Affects connective tissue, muscles, CNS, CVS
108
What is a treatment of homocystinuria?
```
Low-methionine diet
Avoid milk, meat, fish, cheese, eggs
Nuts, and peanut butter also
contain methionine
Cysteine, Vit B6, Betaine, B12 & Folate supplement
```
109
Why is homocystinuria often misdiagnosed?
In children, the symptoms of homocystinuria are very similar to the symptoms form marfans syndrome and children can easily be misdiagnosed. In homocystinuria protein structure is disrupted. Both have similar clinical features such as skeletal deformities and lens dislocation.
110
In homocystinuria build up of what molecules cause disease symptoms?
Homocysteine and methionine
111
How is homocystinuria detected?
Elevated homocysteine and methionine in plasm and the presence homocystine in urine.
112
How are the clinical problems of homocystinuria?
Elevated plasma Cystathionine
homocysteine shown to be associated with cardiovascular disease
Disorders of connective tissues, muscle and CVS. Excess homocysteine causes damage to collagen and elastic fibres in connective tissue. Metabolites of methionine are toxic to neurones and cause neurological dysfunction.
