Protein and Amino Acid Metabolism Flashcards
(172 cards)
1
Q
Give 8 nitrogen containing compounds in the body?
A
Amino acids, Proteins, Purines, Pyrimidines, Porphyrins (haem), Creatine, Neurotransmitters (e.g. dopamines, Some hormones (e.g. adrenaline)
2
Q
What is creatinine?
A
Breakdown product of creatine and creatine phosphate
3
Q
What can creatinine be used as?
A
A useful clinical marker
4
Q
Where is creatinine produced?
A
In muscle
5
Q
What can creatine phosphate be used as?
A
A very short term energy supply of ATP in skeletal muscle
6
Q
At what rate is creatinine usually produced?
A
Constant rate depending on muscle mass
7
Q
How is creatinine excreted?
A
Filtered via kidneys into urine
8
Q
What is creatinine excretion over a 24 hour period proportional to?
A
Muscle mass
9
Q
What is the result of creatinine excretion over 24hrs being proportional to muscle mass?
A
It can provide an estimate for muscle mass
10
Q
What is creatinine commonly used as an indicator for?
A
Renal function
11
Q
What do raised creatinine levels indicate regarding kidney function?
A
Damaged nephrons
12
Q
Why can’t we use a urine volume to determine nephron damage?
A
Because would vary depending on urine dilution
13
Q
When is the body said to be in N equilibrium?
A
When intake = output
14
Q
What is happening to body protein in N equilibrium?
A
No change in total body protein
15
Q
When is N equilibrium normal?
A
In adults
16
Q
What is happening in positive N balance?
A
Intake > output
17
Q
What happens to body protein in positive N balance?
A
Increase in total body protein
18
Q
When is positive N balance the normal state?
A
In pregnancy, growth or an adult recovering from malnutrition
19
Q
What is negative N balance?
A
When intake
20
Q
What happens to body protein in negative N balance?
A
Net loss of body protein
21
Q
When is negative N balance normal?
A
Never
22
Q
Give 3 causes of negative N balance
A
NAME?
23
Q
Describe the nitrogen balance in a 70kg male
A
- 16g N in from dietary nitrogen
- 16g N in amino acid pool
- 2g N lost in skin, hair and nails
- 14g N lost in N-waste products
24
Q
Where does the N in the amino acid pool go?
A
N-containing compounds, and cycled round to and from body protein
25
How much is there of N-containing compounds in the body of a 70kg male?
60g
26
How much of body protein is there in the body of a 70kg male?
2kg
27
What are the N-waste products?
#NAME?
28
What is given when dietary protein is digested?
Free amino acids
29
Other than dietary protein digestion, how can free amino acids be produced?
By de novo amino acid synthesis
30
What are free amino acids in cycle with?
Cellular proteins in muscle
31
What happens in the cycle between free amino acids and cellular proteins in muscle?
Free amino acids are made into cellular proteins in synthesis, and cellular proteins are made into free amino acids in proteolysis
32
What happens to free amino acids in emergency situations?
They are split into their carbon skeleton and amino group in the liver
33
What happens to the amino group produced when free amino acids are split in emergency situations?
It is converted into urea, and excreted in urine
34
What happens to the carbon skeleton produced when free amino acids are split in emergency situations?
- Glucogenic amino acids undergo gluconeogenesis
| - Ketogenic amino acids are converted to ketone bodies
35
What is a glucogenic amino acid?
One that can be converted to glucose by gluconeogenesis
36
Give 2 glucogenic amino acids
#NAME?
37
What is a ketogenic amino acid?
One that can be converted into ketone bodies
38
Give 2 ketogenic amino acids
#NAME?
39
Give 2 amino acids that are both glucogenic and ketogenic
#NAME?
40
What does wether an amino acid is glucogenic or ketogenic depend on?
The side chain
41
What can protein be mobilised to produce?
Glucose
42
Why is protein mobilised to produce glucose?
To meet the need for glucose of some tissues
43
When does mobilisation of protein reserves occur?
During extreme stress, including starvation
44
How is mobilisation of protein reserves controlled?
Hormones
45
Which hormones control the mobilisation of protein reserves?
- Insulin
- Growth hormone
- Glucocorticoids (e.g. cortisol)
46
What is the effect of insulin and growth hormone on protein?
#NAME?
47
What effect do glucocorticoids have on protein?
- Decrease protein synthesis
| - Increase protein degradation
48
When can excessive breakdown of protein occur?
Cushing’s syndrome
49
What is Cushing’s syndrome caused by?
Excess cortisol
50
What is the result of the excessive breakdown of protein in Cushing’s syndrome?
It weakens the skin structure, leading to striae formation
51
How many different types of R groups are there in amino acids?
20
52
What does an amino acids R group determine?
What type of amino acid it is
53
How do amino acids link together?
Through the formation of peptide bonds
54
How can amino acids be obtained other than dietary intake?
The body can synthesise some amino acids that it requires
55
Where do the carbon atoms for non-essential amino acids come from?
- Intermediates of glycolysis (C3)
- Pentose phosphate pathway (C4 & C5)
- Krebs cycle (C4 & C5)
56
Where does the amino group for non-essential amino acids come from?
#NAME?
57
What are amino acids required for?
Synthesis of other important compounds
58
Give 3 things tyrosine is important for the synthesis of
- Catecholamines
- Melanin
- Thyroid hormones
59
What is histidine important for the synthesis of?
Histamine
60
What is arginine important in the synthesis of?
Nitric oxide
61
What is nitric oxide important for?
Vasaldilation
62
Give 2 things cysteine is important for the synthesis of?
- Hydrogen sulphide
| - Glutathione
63
What is hydrogen sulphide important for?
Signalling
64
What is serine important in the synthesis of?
Sphingosine
65
Give 3 things tryptophan is important in the synthesis of?
#NAME?
66
Give 4 things glycine is important in the synthesis of
- Purines
- Glutathione
- Haem
- Creatine
67
Why is the ability to remove nitrogen from amino acids essential?
To allow the carbon skeleton of amino acids to be utilised in oxidative metabolism
68
What can happen to nitrogen from amino acids once removed?
It can be incorporated into other components or excreted from the body as urea
69
What are the two main pathways that facilitate the removal of nitrogen from amino acids?
#NAME?
70
What enzyme is required for transamination?
Aminotransferase
71
What does aminotransferase do?
Transfers the amino group from amino acid to the keto acid α-ketoglutarate
72
What is the result of the action of aminotransferase?
The amino acid is converted to a keto acid, and the keto acid α-ketoglutarate is converted to glutamate
73
What is the alternative to using the keto acid α-ketogluatarate for transamination?
Using the keto acid oxaloacetate
74
What enzyme is required when using the keto acid oxaloacetate for transamination?
Aspartate aminotransferase
75
What does aspartate aminotransferase do?
Converts the amino acid to a keto acid, and oxaloacetate to aspartate
76
What do all amino transferases require?
The coenzyme pyridoxal phosphate
77
What is pyridoxal phosphate a derivative of?
Vitamin B
78
What are the key aminotransferase enzymes?
- Alanine aminotransferase (ALT)
| - Aspartate aminotransferase (AST)
79
What amino acid conversion does alanine aminotransferase catalyse?
Alanine to glutamate
80
What amino acid conversion does aspartate aminotransferase catalyse?
Glutamate to aspartate
81
What is routinely measured as part of a liver function test?
Plasma ALT and AST levels
82
What do the results of the plasma ALT and AST levels mean?
Aren’t normally present in plasma, so if found, bad
83
Where will plasma ALT and AST increase?
In conditions causing extensive cellular necrosis
84
Give 3 conditions that may cause extreme cellular necrosis
- Viral hepatitis
- Autoimmune liver disease
- Toxic injury
85
What does deamination do?
Liberates amin group as free ammonia
86
Where does deamination mainly occur?
In the liver and kidney
87
What is deamination important for?
- Utilisation of keto acids for energy
| - Deamination of dietary D-amino acids
88
Where are dietary D-amino acids found?
#NAME?
89
What is the problem with ammonia?
It’s very toxic
90
What must be done to ammonia in the body?
Must be removed
91
How is ammonia removed?
#NAME?
92
What happens to ammonia at physiological pH?
It is rapidly converted to ammonium ion
93
Give 3 enzymes that can deaminate amino acids
- Amino acid oxidases
- Glutaminase
- Glutamate dehydrogenase
94
Does urea have a high or low nitrogen content?
High
95
Is urea toxic?
No
96
Is urea hydrophilic or hydrophobic?
Very hydrophilic
97
What is the advantage of urea being very hydrophilic?
It is very water soluble, so can easily excrete in urine
98
Is urea chemically reactive or inert?
Inert
99
How can urea be broken down?
By bacteria
100
What is released when bacteria break down urea?
NH 3
101
How is most urea excreted?
In urine via kidneys
102
What important role does urea perform in kidney tubules?
Osmotic role
103
Where does the urea cycle occur?
In the liver
104
How many enzymes does the urea cycle involve?
5
105
What is the amount of urea normally related to?
Need to dispose of urea
106
Is amount of urea under direct control?
No, just governed by amount of substrate
107
What induces high urea cycle enzyme levels?
A high protein diet
108
What represses urea cycle protein levels?
- Low protein diet
| - Starvation
109
Is the urea cycle regulated?
No, but can be induced
110
When can re-feeding syndrome occur?
When nutritional support is given to severely malnourished patients
111
What causes re-feeding syndrome?
Ammonia toxicity
112
Why does ammonia toxicity occur when re-feeding malnourished patients?
Because the urea cycle has been down regulated, so the body can’t cope with the amount of ammonia being produced
113
How is re-feeding syndrome prevented?
By re-feeding at 5 to 10 kcal per kg per day, raising gradually to full needs within a week
114
What are the risk factors for re-feeding syndrome?
- BMI 15% in 3-6 months
| - ~17 days with little/no nutritional intake
115
What causes defects in the urea cycle?
Autosomal recessive genetic disorders
116
What defects occur in the urea cycle?
Deficiency in one of the enzymes in the urea cycle
117
How often to defects in the urea cycle occur?
~1 in 30,000 live births
118
What do mutations in enzymes involved in the urea cycle cause?
Partial loss of enzyme function
119
Why are defects in the urea cycle only partial losses of enzyme function?
Complete loss would be incompatible with life, and the foetus would die
120
What do defects in the urea cycle lead to?
- Hyperammonemia
| - Accumulation/excretion of urea cycle intermediates
121
What is hyperammonemia?
Too much ammonia in the blood
122
What does the severity of defects in the urea cycle depend on?
- Nature of defect
| - Amount of protein eaten
123
How quickly do severe urea cycle disorders show symptoms?
Within 1 day of birth
124
What happens if severe urea cycle defects are left untreated?
The patient will die
125
What can be the case with mild urea cycle deficiencies?
Symptoms don’t show until early childhood
126
What are the symptoms of urea cycle deficiencies
- Vomiting
- Lethargy
- Irritability
- Mental retardation
- Seizures
- Coma
127
How are urea cycle disorders managed?
- Low protein diet
| - Replace amino acids in diet with keto acids
128
What is the biochemical basic of ammonia toxicity?
It is readily diffusible, so can easily access through the blood brain barrier, and is highly toxic to the brain
129
At what levels must blood levels of ammonia be kept?
Very low- 25-50µmol/L
130
What are the potential effects of too much ammonia?
- Interfere with amino acid transport and protein synthesis
- Disruption of cerebral blood flow
- Alkalisation of blood
- Interfere with metabolism of excitatory amino acid neurotransmitters
- Alteration of blood-brain barrier
- Interfere with TCA cycle
131
Why can excess ammonia interfere with the TCA cycle?
It can react with α-ketoglutarate to form glutamate
132
What are the two mechanisms for the safe transport of ammonia from tissues for disposal?
- Glutamine
| - Alanine
133
How does the glutamine mechanism of safe ammonia transport work?
- Ammonia combined with glutamate to form glutamine
- Glutamine transported in blood to liver or kidneys, where it is cleaved by glutaminase to reform glutamate and ammonia
- In the liver, ammonia is fed into the urea cycle.
- In the kidney, ammonia is excreted directly into urine
134
How does the alanine mechanism of safe ammonia transport work?
- Alanine formed in peripheral tissues by transamination of pyruvate- essentially, pyruvate is combined with ammonia to form alanine
- Alanine is transported in blood to the liver
- In the liver, it is converted back to pyruvate by transamination
- Amino group is fed via glutamate into urea cycle for disposal as urea, and pyruvate is used to synthesise glucose
135
How many inherited diseases involving defects in amino acid metabolism are there?
Over 50
136
What causes defects in amino acid metabolism?
Either total, or more commonly partial, loss of enzyme activity
137
What can happen is problems in amino acid metabolism are left untreated?
They frequently lead to intellectual impairment
138
What does treatment of defects in amino acid metabolism involve?
Restricting specific amino acids in the diet
139
What is the heel prick test?
A test that every child in western countries receives to systematically screen for diseases
140
What diseases are tested for with the heel prick test?
- Sickle cell disease
- Cystic fibrosis
- Congenital hyperthyroidism
- Inborn errors in metabolism
141
What inborn errors in metabolism are tested for using the heel prick test?
- Phenylketonuria
- Maple syrup urine disease
- Isovaleric acidaemia
- Glutaric aciduria
- Homocystinuria
142
Why are the diseases in the heel prick test tested for?
Because something, often dietary modification, can be done about them, but if not done as soon as possible, can lead to the development of things such as mental retardation
143
What is the most common inborn error of amino acid metabolism?
Phenylketonuria (PKU)
144
What causes PKU?
Deficiency in phenylalanine hydroxylase
145
What is the inheritance pattern of PKU?
Autosomal recessive
146
Where is the affected gene in PKU?
Chromosome 12
147
What is the result of the lack of phenylalanine hydroxylase?
Accumulation of phenylalanine in tissue, plasma and urine
148
How can PKU be detected?
Phenyl ketones in urine and musty smell
149
What is the treatment for PKU?
#NAME?
150
What high protein foods should be avoided in PKU
- Meat
- Milk
- Eggs
151
What are the symptoms of PKU?
- Severe intellectual disability
- Developmental delay
- Microcephaly (small head)
- Seizures
- Hypo-pigmentation
152
How can the symptoms of PKU be avoided?
Early intervention
153
What causes the symptoms of PKU?
Not producing enough tyrosine
154
Why is not enough tyrosine produced in PKU?
No phenylalanine hydroxylase, so phenylalanine not converted to tyrosine
155
What pathways are affected by lack of tyrosine?
#NAME?
156
What builds up in the blood in PKU?
Phenylalanine
157
Where does the phenylalanine come from?
Dietary protein and endogenous protein
158
What does the build up of phenylalanine in the blood lead to?
Accumulation of phenylketones
159
Why does build up of phenylalanine in the blood lead to accumulation of phenylketones?
Because phenylalanine is converted to phenylpyruvate by transamination, which is then converted into phenylacetate and phenyllactate
160
What causes homocystinurias?
Problems breaking down methionine
161
What is the result of problems breaking down methionine?
Excess homocystine excreted in urine
162
What is homocystine?
2 homocysteines linked together by a disulphide bond- the oxidised fomr of homocysteine
163
What is the inheritance pattern of homocystinurias?
Autosomal recessive
164
What defect causes homocystinurias?
In cystathionine
165
What cystathionine defect is most common?
ß-synthase
166
What do homocystinurias affect?
#NAME?
167
What is the treatment for homocystinurias?
- Low methionine diet
- Avoid meat, milk, fish, cheese, nuts and eggs
- Cysteine, Vit B 6 , betaine, B 12 , and folate supplements
168
What accumulates in homocystinurias?
Methionine and homocysteine
169
Why does methionine and homocysteine accumulate in homocystinurias?
No cystathionine ß-synthase, so homocysteine not converted to cystathionine. Because homocysteine not removed, methionine also accumulates because they interconvert into each other
170
What is the result of the lack of conversion into cystathionine in homocystinurias?
There is a consequent lack of cysteine, which comes from cystathionine
171
What is the homocysteine to methionine conversion promoted by?
- Betaine
- B 12
- Folate
172
What is elevated plasma homocysteine shown to be associated with?
Increased risk of cardiovascular disease
