MEH session 3 Flashcards
1
Q
How is alcohol metabolised?
A
Alcohol oxidised by alcohol dehydrogenase to acetaldehyde and then to acetate by aldehyde dehydrogenase.
Acetate is conjugated to coenzyme A to form acetyl~CoA and used in TCA cycle or for fatty acid synthesis
NAD+ is reduced to NADH in these reactions
2
Q
What is the recommended limit for alcohol consumption?
A
14 units/week spread over at least 3 days for both women and men
3
Q
How many grams of alcohol is 1 unit?
What is the rate of metabolism of alcohol
A
8g of alcohol = 1 unit
Rate of elimination is approximately 7g / hour
4
Q
Acetaldehyde is extremely toxic. How is its toxicity kept to a minimum?
A
Aldehyde dehydrogenase has a very low Km for acetaldehyde and removes it as soon as it is formed.
5
Q
When does acetaldehyde accumulate and what can this cause?
A
Legend the consumption of alcohol is prolonged and excessive.
This can cause liver damage.
6
Q
How can alcohol affect the liver?
A
Acetaldehyde can accumulate if the consumption of alcohol is prolonged and excessive. This can cause liver damage.
In addition, the decrease in the NAD+/NADH ratio and the increased availability of acetyl coA can have significant effects on liver metabolism.
7
Q
What are the clinical consequences of a decrease in NAD+/NADH ratio on liver metabolism in alcoholics?
A
- Hypoglycaemia
- Fatty liver
- Ketoacidosis
- Lactic acidosis
- Gout
8
Q
Why might alcoholics develop hypoglycaemia?
A
Reduced NAD+ for conversion of lactate to pyruvate and conversion of glycerol to dihydroxyacetone phosphate —> less gluconeogenesis
Poor dietary habits of alcoholics may also contribute to the hypoglycaemia as liver glycogen levels tend to be low.
9
Q
Why might alcoholics develop a fatty liver?
A
Reduced NAD+ for TCA cycle—>Increased availability of acetyl coA —> used in fatty acid synthesis —> fatty acid accumulation —> triacylglycerol —> cannot be transported from liver due to decreased lipoprotein production —> fatty liver
Reduced NAD+ for fatty acid metabolism —> fatty acid accumulation —> triacylglycerol —> cannot be transported from liver due to decreased lipoprotein production —> fatty liver
10
Q
Why might alcoholics develop ketoacidosis?
A
Reduced NAD+ for TCA cycle—> increased availability of acetyl coA —> used in ketone body synthesis —> excess ketone bodies in blood —> ketoacidosis
11
Q
Why might alcoholics develop lactic acidosis?
A
Reduced NAD+ for conversion of lactate to pyruvate —> lactate accumulation in blood
12
Q
Why might alcoholics develop gout?
A
Lactate accumulation in blood —> reduced ability of kidneys to excrete uric acid —> gout
13
Q
What is gout?
A
An inflammatory condition resulting from defective purine metabolism.
Uric acid is a byproduct of purine metabolism
As uric acid levels increase in the blood, crystals of monosodium urate accumulate in joint tissues
Neutrophils try to phagocytise the urate crystals in an attempt to remove them, but are killed by the crystals resulting in release of lysosomal and cytoplasmic enzymes which produce a local cell lysis and inflammation in the affected area (macrophages and mast cells involved)
14
Q
How is gout treated?
A
Allopurinol- inhibits xanthine oxidase and therefore the production of uric acid.
15
Q
What drug can be used in the treatment of alcohol dependence and why?
A
Disulfiram
It inhibits aldehyde dehydrogenase
If the patient drinks alcohol, acetaldehyde accumulates in the blood causing symptoms of a hangover such as nausea.
16
Q
What are free radicals?
A
A free radical is any atom, molecule or ion that contains one or more unpaired electrons and is capable of independent existence.
They are very reactive within cells and tend to acquire electrons from other molecules causing damage (eg. Protein, lipid or DNA)
The reaction can also generate a second radical thereby propagating the damage
17
Q
How is superoxide formed in mitochondria?
A
Most cells use oxygen to oxidise compounds to produce energy.
In the electron transport chain in mitochondria, the final destination for an electron is usually an oxygen molecule which is then combined with protons to produce water.
However, about 0.1-2% of electrons do not reach the end of the chain and they prematurely reduce oxygen to form superoxide.
18
Q
What are the main reactive nitrogen species and how are they formed?
A
Reactive nitrogen species:
Nitric oxide - toxic at high concentrations. Superoxide can react with nitric oxide to produce peroxynitrite
Peroxynitrite - powerful oxidant that damages cells
19
Q
What are the main reactive oxygen species?
A
Superoxide - produced by adding an electron to molecular oxygen
Hydrogen peroxide - can be formed from superoxide, not a free radical but can react with Fe2+ in the fenton reaction to form free radicals. This is readily diffusible
Hydroxyl radical - can be formed from hydrogen peroxide. Most reactive and damaging as it reacts with anything
20
Q
How can damage caused by reactive oxygen species cause cancer?
A
ROS can react with base—>Leads to mispairing and mutation
ROS can react with deoxyribose sugar—> Leads to strand breaks—> in the process of repairing the strand, a mutation may occur
Failure to repair the mutations lead to cancer
21
Q
Why is mitochondrial DNA particularly susceptible to ROS damage?
A
Mitochondrial DNA is particularly is particularly sensitive to ROS damage because since mtDNA is situated near inner mitochondrial membrane where superoxide is formed (superoxide can from hydrogen peroxide which can then form hydroxyl radical)
22
Q
What is the most significant change to a proteins structure caused by ROS?
A
When a ROS takes an electron from a cysteine residue since this can lead to formation of an inappropriate disulphides bond causing a change in protein structure due to misfolding/crosslinking
This leads to a disruption to protein function. Altered protein structure may cause protein degradation.
23
Q
How do free radicals damage membranes?
A
Free radicals (eg. Hydroxyl radical) extract hydrogen atoms from polyunsaturated fatty acids in the membrane lipid
A lipid radical is formed which can react with oxygen to form a lipid peroxyl radical
This initiates a chain reaction as lipid peroxyl radicals extract hydrogen from nearby fatty acids
The hydrophobic environment of the bilayer is disrupted and membrane integrity fails
24
Q
Which disease is lipid peroxidation significant in the aetiology of?
A
Atherosclerosis
25
Give some examples of sources of biological oxidants.
Endogenous:
Electron transport chain
Nitric oxide synthase - production of reactive nitrogen species
NADPH oxidases - enzyme present in the cell membrane of phagosomes - transfers electrons from NADPH across the membrane to couple these to molecular oxygen to generate superoxide radicals that are used in a respiratory burst
Exogenous
Radiation - cosmic rays, UV light, X-rays
Toxins eg. Herbicide
Drugs
26
What is nitric oxide?
```
It is a signalling molecule:
Vasodilation
Neurotransmission
S-nitrosylation
It activates cyclic GMP to
```
It is toxic at high levels as some cells use it to form peroxynitrite. This is a highly reactive molecule capable of oxidising a variety of molecules.
27
What are the different types of nitric oxide synthases and what do they do?
Inducible nitric oxide synthase
Produces high NO concentrations in phagocytes for a direct toxic effect
Endothelial nitric oxide synthase
Produces NO for vasodilation
Neuronal nitric oxide synthase
Produces NO for neurotransmission
Nitric oxide synthases use NADPH to reduce arginine into citrulline and nitric oxide
28
What is the respiratory burst?
Occurs in phagocytes such as neutrophils and monocytes
NADPH oxidase is a membrane-bound complex on the cell membrane of phagosomes which transfers electrons from NADPH across the membrane to couple these with molecular oxygen and form superoxide which forms hydrogen peroxide
Hydrogen peroxide can combine with chloride to form hypochlorite which kills the bacteria
Induced nitric oxide synthase forms nitrogen oxide
Nitrogen oxide can be converted to peroxynitrite which destroys the bacteria
In doing so, the cell is usually destroyed but surrounding bacteria or fungal cells are also destroyed. Therefore, this is an important part of the body's immune response to infection.
29
What does NADPH oxidase do?
It is a membrane bound enzyme complex in the membrane of phagosomes which transfers electrons from NADPH across the membrane to couple these to molecular oxygen and generate superoxide radicals
30
What are our cellular defences against free radicals?
1. Superoxide dimutase (SOD) and catalase
2. Glutathione
3. Free radical scavengers
31
What does superoxide dimutase and catalase do?
Superoxide dimutase counters the damaging effects of superoxide by catalysing its conversion to hydrogen peroxide and oxygen
Catalase converts hydrogen peroxide to oxygen and water
32
Why is catalase an important enzyme in immune cels?
Catalase catalyses the conversion of hydrogen peroxide to water and oxygen.
It protects immune cells against the oxidative burst as they have the enzyme NADPH oxidase which form free radicals
33
What is glutathione and describe its structure.
Glutathione is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and the amine group of cysteine.
It is an antioxidant synthesised by the body to protect against oxidative damage.
34
Glutathione is antioxidant synthesised by the body to protect against oxidative damage. How does it do this?
The thiol group of the cysteine residue donates an electron to ROS. It then reacts with another glutathione molecule to form a disulphides bond
Glutathione peroxidase is required for this reaction
35
What does glutathione peroxidase require to function and what reaction does this catalyse?
Selenium
Glutathione peroxidase allows two reduced glutathione molecules to donate their electron to ROS and form a disulphide bond
36
How is oxidised glutathione reduced back to glutathione?
By the enzyme glutathione reductase
This catalyses the transfer of electrons from NADPH (mostly produced by the pentose phosphate pathway) to the disulphide bond of GSSG. This recycles the glutathione so it is once again ready to protect against ROS damage.
37
What is the first line of defence against ROS?
Glutathione as it is so abundant in cells
38
Why is the pentose phosphate pathwayessential for the protection against free radical damage?
Pentose phosphate pathway is the only pathway which produces NADPH
Electrons from NADPH are added to the disulphide bond of oxidised glutathione by glutathione reductase to recycle glutathione.
Glutathione is an essential anti-oxidant synthesised by the body.
39
Which vitamins have important antioxidant roles?
Vitamin E - lipid soluble so important in protecting against lipid peroxidation
Vitamin C - water soluble, important in regenerating the reduced form of vitamin E
40
How do free radical scavengers reduce ROS damage?
They donate electrons to free radicals in a non enzymatic reaction
41
What is oxidative stress?
Usually cells have sufficient antioxidant capacity to cope with the production of ROS
Oxidative stress occurs when:
The production of ROS is excessive
Levels of antioxidants are low
42
What happens in galactosaemia?
```
There is a deficiency in either:
Galactokinase
Uridyl transferase
UDP-epimerase
These leads to a build up of galactose which is converted to galactitol by aldose reductase. Aldose reductase requires NADPH to work so this consumes NADPH
```
43
In galactosaemia, there is increased activity of the enzyme aldose reductase so excess NADPH is consumed. There is also reduced NADPH in people with G6PDH deficiency. What reaction that requires NADPH is disrupted?
Glutathione reductase uses NADPH as an electron donor to convert glutathione back to its reduced form
NADPH is a structural component of catalase. Catalase converts hydrogen peroxide to water and oxygen
This leaves the cell susceptible to oxidative damage.
44
What happens in glucose-6-phosphate dehydrogenase deficiency?
The production of NADPH is limited as this is the first enzyme in the pentose phosphate pathway
45
Which cells are particularly affected by reduced NADPH levels?
Red blood cells since they cannot synthesise damaged proteins with new ones as they have no nucleus.
Therefore, when the individual is exposed to oxidative stress (infection, drugs, beans), aggregates of cross-linked haemoglobin accumulate (Heinz bodies).
46
What are Heinz bodies?
Dark staining within red blood cells resulting from precipitated haemoglobin.
This binds to the cell membrane altering flexibility.
There is increased mechanical stress when they squeeze through capillaries.
The spleen removed bound heinz bodies resulting in blister cells.
47
What metabolic disease are Heinz bodies a clinical sign of?
Glucose 6 phosphate dehydrogenase deficiency
48
How is paracetamol usually metabolised by the liver?
Conjugation with glucuronide or sulphate in the liver yielding relatively non-toxic metabolites
49
What is a toxic dose of paracetamol?
About 10g - conjugation with glucoronide or sulphate quickly becomes saturated
50
What happens when a toxic dose of paracetamol is taken
Paracetamol metabolism produces the metabolite, N-acetyl-p-benzo-quinone imine (NAPQI)
NAPQI is extremely toxic to hepatocytes because:
it is a strong oxidising agent so causes covaelnt binding in hepatic proteins together
undergoes conjugation with glutathione, depleting its levels in important anti-oxidant hepatocytes leading to oxidative damage (lipid peroxidation, damage to proteins, damage to DNA)
This results in destruction of liver cells
Liver failure occurs over a period of several days eventually causing death
51
What is the treatment for paracetamol overdose?
Acetylcysteine - if initiated within hours after paracetamol overdose, prognosis is good
It replenishes glutathione allowing the liver to safely metabolise NAPQI
52
Hat are the major nitrogen containing compounds in the body?
Amino acids
Proteins
DNA
RNA
```
Smaller amounts of others:
Creatine
Porphyrins
Neurotransmitters
Hormones
```
53
What is creatinine and how is it different to creatine?
Creatinine is a breakdown product of creatine and creatine phosphate in muscle. Creatine can be used as an immediate energy store in muscle.
54
What is the clinical relevance of measuring creatinine in the blood and urine?
It is filtered via kidneys into urine.
It is usually produced at a constant rate and creatinine urine excretion over 24 hours is proportional to muscle mass (unless muscle is wasting).
Uses:
Renal function - raised level on damage to nephrons
Provides an estimate of muscle mass
55
What does nitrogen balance mean?
In healthy adults there is a steady state in which the amount of nitrogen taken into the body equals the amount of nitrogen lost from the body and the individual is said to be in N-balance.
56
How does nitrogen enter the body?
Protein (we eat approximately 100g of protein, 16% of protein is nitrogen so 16g nitrogen a day)
57
How dees nitrogen leave the body?
```
Urea
Creatinine
Ammonia
Uric acid in the urine, sweat, faeces
Direct loss of protein in skin, hair, nails etc from the body
```
58
Give some examples when an individual is in positive N-balance?
```
N intake > N loss
Periods of active growth
Pregnancy
Tissue repair
Convalescence
```
59
Give some examples when an individual is in negative N-balance.
N intake < N loss
Starvation
Malnutrition
Trauma
60
What does protein turnover mean?
All body proteins undergo continuous breakdown and resynthesis. Normally the rate of protein breakdown equals the rate of resynthesis. Protein turnover is not a random process and mechanisms exist for identifying proteins that are to be degraded.
61
What does the rate of protein turnover depend on?
All body proteins undergo continuous breakdown and resynthesis. Normally the rate of protein breakdown equals the rate of resynthesis. Protein turnover is not a random process and mechanisms exist for identifying proteins that are to be degraded.
62
What is the difference between glucogenic and ketogenic amino acids?
Ketogenic amino acids produce acetyl coA so can be used for the synthesis of ketone bodies. Their catabolism produces either:
- Acetyl coA directly
- Acetoacetyl coA
```
Glucogenic can be used for glucose synthesis by gluconeogenesis. Their catabolism produces either:
Pyruvate
Oxaloacetate
Fumarole
Alpha-ketoglutarate
Succinate
```
Some amino acids are both ketogenic and glucogenic
63
Which hormones have the following effects on skeletal muscle, adipose tissue and the liver?
Stimulate the uptake of amino acids
Stimulate protein synthesis
Inhibit protein degradation
Insulin
| Growth hormone
64
Which hormones have the following effects on skeletal muscle, adipose tissue and the liver?
inhibits the uptake of amino acids
Inhibits protein synthesis
stimulates protein degradation
Cortisol
65
Which hormones:
Inhibit the uptake of amino acids
Increase protein degradation
Glucocorticoids eg. Cortisol
66
In which disease does striae formation occur due to excessive breakdown of protein?
Cushings syndrome - excess cortisol
67
Which are the essential amino acids?
```
Isoleucine
Lysine
Threonine
Histidine
Leucine
Methionine
Phenylalanine
Tryptophan
Valine
```
68
What amino acids are conditionally essential and when?
Arginine
Periods of active growth
Pregnancy
Tyrosine
Synthesised from phenylalanine so may become essential if the diet is low in phenylalanine
Cysteine
Synthesised from methionine so may become essential if the diet is low in methionine
69
How are non-essential amino acids synthesised?
The carbon atoms for the non-essential amino acids come from:
intermediates of glycolysis (C3)
the pentose phosphate pathway (C4 and C5)
the Krebs cycle (C4 and C5)
The amino group comes form:
Other amino acids by the process of transamination
Ammonia
70
What substances in the body are produced from tyrosine?
Melanin
Thyroid hormones
Catecholamines
71
What substances in the body are produced from glycine?
Purines
Glutathione
Porphyrins
Creatine
72
What substance in the body is produced from histidine?
Histamine
73
What signalling molecule is synthesised from arginine?
Nitric oxide
74
Where are amino acids catabolised?
Liver is major site
75
Are all amino acids catabolised in the same way?
No, they each have their own pathway but share common features - end up converting the amino acid to important organic precursor molecules
76
How is the amino group of the amino acid removed and what happens to this amino group?
Transamination/deamination
| It is converted to urea which is excreted from the body in urine
77
What is transamination?
| Which enzyme is involved?
Major mechanism for removal of -NH2 group from amino acids. They remove the amino group from one amino acid and transfer it onto another.
Enzymes involved are aminotransferases (transaminases) and they are specific for individual amino acids or groups of structurally similar amino acids
78
What do most transaminases use to funnel the amino group?
What is the exception to this rule?
They use alpha ketoglutarate to funnel the amino group to glutamate
Exception:
Aspartate aminotransferase uses oxaloacetate to funnel the amino group to aspartate.
79
Which hormone stimulates transaminase synthesis in the liver?
Cortisol
80
Aspartate is an important intermediate in the synthesis of...
Urea
81
What do all aminotranferases require to function?
Vitamin B6
82
Which two transaminases are clinically important as they are measures in the serum of patients to assess liver function. State their function.
Alanine aminotransferase (ALT)
Alanine + alpha ketoglutarate ---> pyruvate + glutamate
Aspartate aminotransferase (AST)
Glutamate + oxaloacetate ---> keto acid + aspartate
83
When is serum ALT and AST elevated?
In conditions that cause extensive liver necrosis such as:
Viral hepatitis
Autoimmune liver disease
Toxic injury
84
What is deamination?
Several enzymes of varying specificity found in the liver and kidney react with amino acids to remove the NH2 group as free NH3.
(Can only occur in places where the ammonia will be quickly converted to urea as it has toxic effects)
85
What are amino oxidases? Where is their activity greatest?
L and D amino acid oxidase - low specificity enzymes that convert amino acids to keto acids and NH3. Keto acids are not optically active and can be utilised for energy
Activity greatest in the liver.
86
Where are D-amino acids found?
| Why can't D amino acids be used for protein synthesis?
They are found in plant and bacterial cells so enter the body through diet.
The proteins would be structurally abnormal and non-functional.
87
Which enzymes are involved in deamination?
Amino acid oxidases
Glutaminase
Glutamate dehydrogenase
88
Why is urea an effective way of disposing unwanted nitrogen?
Very soluble in water
Non-toxic and metabolically inert
High nitrogen content
Useful osmotic role in kidney tubules
89
In transamination, glutamate and aspartate is formed. What cycle can these feed into?
The urea cycle
90
Where does the NH2 groups of urea come from?
NH2 groups of urea come from:
--->NH4 - from the actions of enzymes in the liver that deaminate amino acids releasing NH3
from NH3 produced by gut bacteria that enters liver from the portal circulation
--->Aspartate - from oxoaloacetate by transamination (glutamate can be converted to aspartate via aspartate aminotransferase)
Carbon comes from:
---> CO2 - from the citric acid cycle in the mitochondria
91
How is urea synthesis regulated?
Enzymes of the cycle are not subjected to feedback inhibition by the end product of the cycle as the function of the cycle is to dispose of ammonia as urea
However, enzymes of the cycle are inducible- a high protein diet induces the enzymes whereas a low protein diet or starvation represses enzymes
92
Why is it important that protein is re-introduced slowly into the diets of starving individuals?
Starving individuals have a very low activity of the enzymes of the cycle
Too much protein too soon will lead to hyperammonaemia as excess amino acids are degraded
This is refeeding syndrome
93
What do defects in the enzymes involved in the urea cycle cause?
Hyperammonaemia (high blood NH4+ concentration)
Accumulation/excretion of a particular urea cycle intermediate
94
What symptoms may occur in inherited diseases of the urea cycle?
```
Vomiting
Lethargy
Irritability
Mental retardation
severe cases:
Seizures
Coma
Eventually death
```
95
How are inherited diseases of the urea cycle treated?
Low protein diets
Diets in which the keto acids of the essential amino acids are used to replace the amino acids themselves - keto acids are converted to amino acids using some of the NH4+ thereby lowering its concentration in the tissues
96
What is the normal peripheral concentration of ammonia?
Very low (25-40micromoles/L)
97
How does hyperammonaemia affect the TCA cycle?
Molecular basis of the toxic effect of ammonia may involve its reaction with alpha-ketoglutarate to from glutamate in mitochondria via glutamate dehydrogenase (opposite of glutamate aminotransferase)
--->Removes alpha ketoglutarate from the TCA cycle which slows and disrupts energy supply to brain cells
98
What are the effects of hyperammonaemia?
```
Interference with metabolism of excitatory amino acid transmitters (glutamate and aspartate)
Alteration of blood-brain barrier
Interference of TCA cycle
pH affects- alkaline
Disruption of cerebral blood flow
```
99
How is ammonia detoxified via glutamine?
Converted to glutamine
Glutamine transported in blood to liver where it is cleaved by glutaminase to form glutamate and ammonia
An liver, ammonia is fed into urea cycle, in kidneys it is secreted directly in the urine
100
How is ammonia detoxified via alanine?
Ammonia is combined with pyruvate to form alanine
Alanine is transported to the liver where it is converted back to pyruvate by transamination
Amino group fed via glutamate into urea cycle for disposal whereas pyruvate is used to synthesise glucose which can be fed back to tissues
101
Why is a defect in an enzyme that breaks down an amino acid harmful?
The amino acid and/or products of its breakdown accumulate and these may be toxic themselves and/or may be metabolised to toxic products
The toxicity may produce mental retardation and developmental abnormalities
102
What is the treatment for a defective/absent enzyme involved in amino acid metabolism?
Restricting the amount of a particular amino acid in the diet by using a special diet. This must be done in early life.
103
How is phenylketonuria screened for in newborns along with other genetic diseases and why?
Heel prick test
The toxicity may produce mental retardation and developmental abnormalities if not treated early
104
How is PKU diagnosed?
- large amounts of phenylalanine in tissue, plasma and urine
- phenylketones produced from phenylalanine found in urine
105
Which enzyme is defective in most cases of PKU?
Phenylalanine hydroxylase - first step in the metabolism of phenylalanine in its oxidation to tyrosine
106
Wat are the symptoms of PKU?
Inhibition of brain development
- phenylalanine is a large neutral amino acid (LNAA)
- competes for transport across the blood brain barrier via Large Neutral Amino Acid Transporter (LNAAT)
- excess phenylalanine can saturate the transporter
- levels of other LNAA in the brain decrease
- protein/neurotransmitter synthesis inhibited
Severe intellectual disability
Seizures
Microcephalic
Hypopigmentation
107
Why is catecholamine synthesis affected in most cases of PKU?
Most cases of PKU are caused by a defective phenylalanine hydroxylase enzyme.
This converts phenylalanine to tyrosine.
Tyrosine forms catecholamines, dopamine, melanin, thyroid hormone
108
How is phenylketonuria treated?
Strictly controlled low phenylalanine diet
109
How is homocytinuria diagnosed?
Elevated levels of homocysteine and methionine in plasma
| Presence of homocystine in the urine
110
Which enzyme is most commonly defective in PKU?
Phenylalanine hydroxylase
111
Which enzyme is most commonly defective in homocystinuria?
Cystathionone beta synthase enzyme
Normally converts homocysteine to cystathione
112
What are the symptoms of homocystinuria?
Very similar to Marfan's syndrome and can be easily misdiagnosed..
in marfans syndrome there is lack of expression of fibriillin gene and in homocystinuria the structure of fibrillin is disrupted
113
How is homocystinuria treated?
Low methionine diet
Avoid milk, meat, fish, cheese, eggs, nuts, peanut butter
Cysteine, vitamin b6, vitamin b12 and folate supplements
114
What is chronic granulomatous disease?
There is a genetic defect in the NADPH oxidase complex present on the membrane of phagosomes. This enzyme transfers electrons from NADPH across the membrane to couple these to molecular oxygen and generate superoxide.
This enhances susceptibility bacterial infections:
- atypical infections
- pneumonia
- abscesses
- impetigo
- cellulitis
115
What is the difference between having a uridyl transferase deficiency, galactokinase deficiency and having a UDP-galactose epimerise efficiency?
Uridyl transferase deficiency
Galactitol accumulation ---> cataracts
Galactose 1-P accumulation ---> in liver, kidney, GIT and caused brain damage
Galactokinase deficiency
Galactitol accumulation---> cataracts
UDP-galactose epimerise deficiency
Galactitol accumulation ---> cataracts
Galactose 1-phosphate accumulation ---> in liver, kidney, GIT and causes brain damage
Treatment: When put on a galactose free diet, unable to make galactose from glucose. Galactose is required for certain glycoproteins.
116
What term is used to describe scarring of the liver caused by continuous long-term liver damage?
Cirrhosis
117
What is a metabolic response to chronic alcohol consumption?
Increased synthesis of fatty acids and ketone bodies due to increased acetyl-coA from alcohol oxidation
118
Reactive oxygen species damage proteins by protein glycosylation.
True or false?
False.
Glycosylation is a normal post-translational modification to some proteins, not a consequence of oxidative damage,
Oxidative damage to proteins by ros INCLUDES:
-hydroxylase adducts
-di-tyrosine dimers
-inappropriate disulphide bond formation
-formation of ring open species
119
Which enzyme is involved in protecting cells from oxidative damage by converting superoxide to hydrogen peroxide and oxygen?
Superoxide dismutase (SOD)
120
Which enzyme protects cells from oxidative damage by converting hydrogen peroxide to water and oxygen?
Catalase
121
Which fat soluble vitamin plays an important role in protecting cells against oxidative damage by acting as a free radical scavenger?
Vitamin E - protects against lipid peroxidation
122
In paracetamol overdose, which toxic metabolite accumulates in the liver causing damage?
NAPQI
123
Which effect would the hormone insulin have on the process of protein degradation?
Decrease in activity
If you have just eaten a meal, there would be sufficient amino acids derived from the ingested protein so there would be no need to degrade body protein.
124
From which amino acid does the body synthesise adrenaline?
Tyrosine (synthesised from phenylalanine). This is the precursor for:
Catecholamines: adrenaline, noradrenaline, dopamine
Thyroid hormones, T3 and T4
125
Which keto acid is used by aminotransferase enzymes to funnel the amino group of other amino acids to glutamate?
Alpha keto glutarate
126
Downregulation of the enzymes of the urea cycle resulting from insufficient protein intake can result in which disease state?
Refeeding syndrome
127
Which amino acid is utilised for the transport of ammonia from peripheral tissues to the liver?
Alanine and glutamine
Ammonia produced in peripheral tissues is very toxic to cells and must be disposed of safely. Ammonia is therefore used to transaminate pyruvate to produce alanine. The alanine is then transported in blood to the liver where it is converted back to pyruvate by transamination. The amino group is then fed via glutamate into urea cycle for disposal as urea and the pyruvate is used in gluconeogenesis to synthesise glucose which can be fed back to the tissues.
The other amino acid utilised in a similar way is glutamine. Ammonia is combined with glutamate to form glutamine. Glutamine is then transported in blood to the liver or kidneys where it is cleaved by glutaminase to reform glutamate and ammonia. In liver the ammonia is fed into urea cycle for disposal as urea whereas in the kidney it is excreted directly in urine.
128
What is cystine?
Two cysteine amino acids bound together by a disulphide bond
128
What is homocysteine and how is it synthesised?
It is a homologue of cysteine differing by an additional CH2
Synthesised from methionine by the removal of the terminal methyl group
It is a non-protein amino acid
129
What is homocystine?
Two homocysteines joined together by a disulphide bond. The form of homocysteine that appears in the urine of homocystinuria patients is homocystine
130
How can you differentiate homocystinuria and marfans syndrome?
Both cause:
Lens dislocation
Skeletal deformities
CT damage
In homocytinuria, symptoms are seen which are not seen in marfans syndrome:
metabolites of methionine are toxic to neurones and can cause neurological problems
