Session 3 Flashcards
(149 cards)
1
Q
Are sugars normally present in the urine?
A
No - usually fully reabsorbed in the kidneys
2
Q
If sugars are detected in the urine what can this indicate? (2)
A
Either…
Levels of sugar in the blood are elevated
Kidney damage
3
Q
Do proteins normally enter the filtrate that passes through the kidneys? Why?
A
No - too large and usually charged
4
Q
Explain why sugar may be seen in the urine of someone with elevated blood sugar levels?
A
There is a large concentration of sugar which exceeds the capacity of the reabsorption process in the kidney tubule - therefore some sugar remains in the filtrate and appears in the urine
5
Q
What is the renal threshold of a substance?
A
The concentration above which the substance will be excreted in the urine
6
Q
Where is the vast majority of alcohol metabolised in the body?
What happens to any remaining alcohol? (2)
A
Vast majority metabolised by the liver
Excreted passively in the urine OR on the breath
7
Q
What reactions does alcohol undergo in the liver? What sorts of reactions are these?
A
Alcohol —> Acetaldehyde —> Acetate
Oxidation
8
Q
Which enzyme catalyses the conversion of alcohol to acetaldehyde?
A
Alcohol dehydrogenase
9
Q
Which enzyme catalyses the conversion of acetaldehyde to acetate?
A
Aldehyde dehydrogenase
10
Q
Which toxic metabolite is produced in alcohol metabolism? What can accumulation of this substance cause?
A
Acetaldehyde
Hangover
11
Q
The acetate produced in the metabolism of alcohol is used to…
A
Produce acetyl CoA
12
Q
The acetyl CoA produced from acetate in alcohol metabolism can be used for… (2)
A
Fatty acid synthesis
TCA cycle
13
Q
Give two other ways that alcohol can be metabolised rather than through oxidation by the usual enzymes in the liver
A
Can be oxidised by…
CYP450
Catalase (In the brain)
14
Q
What is the recommended limit for alcohol consumption per week?
A
14 units/week (spread over at least 3 days)
15
Q
1 unit of alcohol equates to how many grams…
A
~8g (half a beer, small wine)
16
Q
How much alcohol is eliminated from the body in an hour…
A
~7g
17
Q
Prolonged and excessive alcohol consumption can cause…
A
Acetaldehyde accumulation —> Liver Damage (cirrhosis)
18
Q
What is produced in the conversion of alcohol to acetaldehyde and then acetate?
A
NADH
19
Q
What can the increased acetyl-CoA produced in chronic alcohol consumption result in? How?
A
Fatty liver
Increased synthesis of fatty acids + TAGs in the liver
20
Q
What can the decrease in the NAD+/NADH ratio as a result of chronic alcohol consumption result in? (3)
A
Hypoglycaemia
Gout
Lactic acidosis
21
Q
How can the decrease in the NAD+/NADH ratio seen in chronic alcohol consumption cause hypoglycaemia?
A
There is inadequate NAD+ for glycerol metabolism and then a deficit in gluconeogenesis leading to hypoglycaemia
22
Q
How can the decrease in the NAD+/NADH ratio seen in chronic alcohol consumption cause gout and lactic acidosis?
A
There is inadequate NAD+ for the conversion of lactate to pyruvate, lactate accumulates in the blood (lactic acidosis)
Kidney’s ability to excrete uric acid reduced —> urate crystals accumulate causing gout
23
Q
How can the decrease in the NAD+/NADH ratio seen in chronic alcohol consumption contribute to fatty liver?
A
There is inadequate NAD+ for fatty acid oxidation, therefore used for TAG synthesis instead
24
Q
What is disulfiram used for?
A
The treatment of chronic alcohol dependence
25
How does disulfiram help in the treatment of chronic alcohol dependence?
Works as an inhibitor for aldehyde dehydrogenase
So if the patient drinks alcohol, acetaldehyde will accumulate and cause the symptoms of a hangover
26
What is oxidative stress?
Where there is an imbalance between the production of free radicals and the ability of the body to counteract their harmful effects
27
Give an example of cell defences against oxidative stress
Antioxidants
28
Oxidative stress can be as a result of either reactive ______________ or reactive ___________ species
Oxygen
Nitrogen
29
What is a free radical?
An atom or molecule that contains one or more unpaired electrons
30
Free radicals are very _______ and tend to acquire __________ from other atoms, molecules or ions
Reactive
Electrons
31
State three reactive oxygen species
```
Superoxide (O2-)
Hydrogen Peroxide (H2O2)
Hydroxyl Radical (OH*)
```
32
State 2 reactive nitrogen species
```
Nitric oxide (NO*)
Peroxynitrite (ONOO-)
```
33
How is superoxide produced from molecular oxygen?
With the addition of an electron
34
Is hydrogen peroxide a free radical?
No, as it has no unpaired electron but is a reactive oxygen species
Can react to produce free radicals (e.g. With Fe2+)
35
Which is the most damaging and reactive free radical?
Hydroxyl radical
36
How is the reactive nitrogen species, peroxynitrite produced?
Reaction of nitric oxide and superoxide
37
Is peroxynitrite a free radical?
No, but a powerful oxidant that can damage cells
38
How can ROS damage DNA? (2)
Reacts with base to modify it causing mispairing/mutation
Reacts with sugar causing a strand break and mutation on repair
39
What can be used as a measurement of oxidative damage to DNA?
The amount of 8-oxo-dG present in cells
40
How can reactive oxygen species do damage to proteins? (2)
They can damage the backbone leading to fragmentation
They can damage the side chains and modify the amino acids causing a change in protein structure and gain/loss of function
Both can lead to increased protein degradation of the damaged protein
41
Disulphide bonds play and important role in the _________ and _________ of some proteins
These proteins are usually...
Stability
Folding
Secreted proteins/extracellular parts of membrane proteins
42
Disulphide bonds are formed between...
Thiol groups of cysteine residues
43
What effect can ROS have on proteins with regards to their disulphide bonds?
Inappropriate disulphide bonds can be formed if ROS take electrons from cysteine residues
44
How can ROS damage (membrane) lipids?
Free radicals extract hydrogen atoms from a polyunsaturated fatty acid in the lipid
This results in the formation of a lipid radical
Lipid radical reacts with oxygen to form lipid peroxyl radical
Chain reaction formed with lipid peroxyl radical extracting hydrogen from nearby fatty acids
The hydrophobic environment of the bilayer is disrupted
Membrane integrity fails
45
What product is formed by the reaction of a lipid radical with oxygen? This product can cause damage by...
Lipid peroxyl radical
Extracting hydrogen atoms from polyunsaturated fatty acids in other membrane lipids
46
Give 3 examples of endogenous sources of biological oxidants...
Electron transport chain
Nitric oxide synthase
NADPH oxidases
47
Give 4 examples of exogenous sources of biological oxidants...
Radiation
Pollutants
Drugs
Toxins
48
Give some examples of radiation that can be exogenous sources of biological oxidants...
Cosmic rays
UV light
X rays
49
Give an example of a drug that is an exogenous source of biological oxidants....
Give an example of a toxin that is an exogenous source of biological oxidants...
Primaquine (anti-malarial)
Paraquat (herbicide)
50
How does the electron transport chain contribute to the formation of free radicals?
Electrons that pass through the electron transport chain in the oxidation of NADH and FADH2 can occasionally escape and react with dissolved oxygen to form superoxide radicals
51
Nitric oxide synthase catalyses which reaction?
Arginine + NADPH + O2 ---> Citrulline + NO* + NADP+ + H2O
52
Other than having toxic effects at high levels what other function does nitric oxide have in the body?
Acts as a signalling molecule (important in vasodilation, neurotransmission etc.)
53
How many types of nitric oxide synthase are there?
Nitric oxide synthase converts arginine to...
3
Citrulline and NO*
54
What are the three types of nitric oxide synthase? What are their functions?
iNOS - produces high NO concentrations in phagocytes for toxic effects
eNOS - endothelial NOS for signalling
nNOS - neuronal NOS for signalling
55
The respiratory burst involves the rapid release of _____________ and ___________ _________ from phagocytic cells
Superoxide
Hydrogen peroxide
56
What is chronic granulomatous disease?
A genetic defect in NADPH oxidase complex that causes enhanced susceptibility to bacterial infections
57
Name some cellular defences against oxidative damage (ROS/RNS)
Superoxide dismutase
Catalase
Glutathione
Vitamin A, C, E
58
How does superoxide dismutase defend against ROS/RNS?
How does catalase defend against ROS/RNS?
Converts superoxide to hydrogen peroxide and oxygen. Important as superoxide is a strong initiator of chain reactions.
Converts the hydrogen peroxide to water and oxygen
59
Where is catalase found in the body?
Widespread, protects against the oxidative burst in immune cells
60
What is glutathione? What is its important function?
A tripeptide (Gly-Cys-Glu)
Protects against oxidative damage
61
How does glutathione help protect the body against oxidative damage?
Thiol group of Cys on glutathione donates electrons to ROS - GSH oxidised to GSSG
62
Which enzyme catalyses the reaction of two molecules of GSH (reduced glutathione) to form GSSG (oxidised form)?
Which cofactor does this enzyme require?
Glutathione peroxidase
Selenium
63
Which enzyme reduces GSSG back to 2xGSH?
Glutathione reductase
64
What role does NADPH play with glutathione? What pathway provides the NADPH for this process?
Electrons are transferred from NADPH to glutathione
Pentose phosphate pathway
65
Give two examples of free radicals avengers? How do they work?
Vitamin C and Vitamin E
Donates hydrogen atom and its electron to free radicals - non-enzymatic
66
Give an example of a lipid soluble antioxidant
Give an example of a water soluble antioxidant
Vitamin E
Vitamin C
67
What specific role does Vitamin E play as antioxidant?
Important for protecting against lipid peroxidation
68
What specific role does Vitamin C play as antioxidant?
Important role in regenerating reduced form of vitamin E
69
What is galactosaemia?
A genetic disorder which affects an individual's ability to metabolise galactose effectively
70
Galactose is produced in the breakdown of which dietary sugar?
Breakdown of lactose into glucose and galactose
71
Galactose in the body is usually used for... (2)
Through the action of which 3 enzymes?
Glycolysis
Gluconeogenesis
Galactokinase
Uridyl transferase
UDP-galactose epimerase
72
What cause galactosaemia?
Deficiency in any of the 3 usual enzymes which metabolise galactose for us in glycolysis or gluconeogenesis
I.e. Galactokinase
UDP-galactose epimerase
Uridyl transferase
73
What happens to the galactose in galactosaemia instead of being used in glycolysis or for gluconeogenesis?
It is converted to galactitol by adolase reductase
74
How does increased activity of adolase reductase in the metabolism of galactose in galactosaemia affect ROS defence?
What condition can this lead to?
Increased activity of adolase reductase consumes more NADPH which is usually a defence against ROS
Cataract
75
How does galactosaemia cause cataract?
Less NADPH due to increased activity of adolase reductase
Less defence against ROS
Denaturing of crystalline protein in lens of the eye
76
Name 3 other symptoms of galactosaemia excluding cataracts?
Hypoglycaemia
Renal failure
Vomiting
77
NADPH is required for the ____________ of GSSG to GSH
How can this be affected by G6PDH deficiency?
Reduction
Limits amount of NADPH available to reduce GSSG back to GSH - less GSH - less damage from oxidative stress
78
What are Heinz bodies? How do they appear under the microscope?
Aggregates of cross-linked haemoglobin within RBCs
Dark staining within RBCs
79
Heinz bodies are a clinical sign of which enzyme deficiency?
G6PDH deficiency
80
What effect do Heinz bodies have on RBCs?
They bind to the cell membrane altering rigidity and lead to increased mechanical stress when RBCs squeeze through small capillaries
81
What role does the spleen play with regards to Heinz bodies?
The spleen removes Heinz bodies, producing blister cells
82
In which cell of the body is paracetamol usually metabolised?
Hepatocytes
83
How is paracetamol usually metabolised at prescribe dosages?
By conjugation with glucuronide or sulphate
84
What happens in hepatocytes if there a high levels of paracetamol present?
The toxic metabolite NAPQI accumulates
85
Which toxic metabolite is produced in the metabolism of high levels of paracetamol?
NAPQI
86
What effects can NAPQI have? (2)
Direct toxic effects resulting in oxidative damage to the liver cell
Glutathione depletion
87
What is the treatment for high levels of paracetamol in the body - e.g. Paracetamol overdose? How does it work?
Acetylcysteine
Replenishes glutathione levels
88
Creatinine is the breakdown product of ___________ and ____________ ____________ in which part of the body?
Creatine
Creatine phosphate
Muscle
89
Creatinine is usually produced at a ___________ rate depending on...
Constant
Muscle mass of the individual
90
How is creatinine usually excreted?
Via the kidneys into the urine
91
Creatinine is a useful clinical marker for what? How?
An estimate of muscle mass
Creatinine urine excretion over 24h is proportional to muscle mass
92
As well as being useful in providing an estimate of muscle mass, creatinine can be used as an indicator of...
Renal function, if raised can indicate damage to nephrons
93
What is the usual reference range for creatinine excreted in the urine per day in...
Males
Females
14-26 mg/kg
11-20 mg/kg
94
What should the overall nitrogen balance in a normal, healthy adult be?
At equilibrium - input = output
95
When is a positive N balance normal? (3)
In growth
In pregnancy
In adult recovering from malnutrition
96
When is a negative N balance normal?
Never
Usually indicates; trauma, infection, malnutrition
97
How is most of the nitrogen lost from the body? How else is it lost from the body?
In waste products lost in faeces/urine
In the loss of skin, hair and nails
98
What is meant by a ketogenic amino acid? Give an example?
An amino acid that is used to synthesis ketone bodies
Lysine
99
What is meant by a gluconeogenic amino acid? Give an example?
Used for gluconeogenesis
Glycine
100
Give an example of an amino acid that is both ketogenic and gluconeogenic?
Tyrosine
101
When does mobilisation of protein reserves take place? By which mechanisms?
During extreme stress - starvation
Under hormonal control
102
Give an example of two hormones that result in an increased rate of protein synthesis and a decreased rate of proteins degradation
Insulin
| Growth hormone
103
Give an example of a hormone that results in an increased rate of protein degradation and a decreased rate of protein synthesis?
Cortisol
| Glucocorticoids
104
In Cushing's syndrome there is excess ________ leading to excessive __________ of proteins.
How does this result in striae formation?
Cortisol
Breakdown
Leads to weakened skin structure
105
The body can synthesise some non essential amino acids.
Where do the carbon atoms for this synthesis come from? (3)
Where do the amino groups for this synthesis come from? (2)
Intermediates of glycolysis
Pentose phosphate pathway
Krebs cycle
From other amino acids by transamination
From ammonia
106
What is the purpose of removing nitrogen (amino group) from amino acids?
It allows the carbon skeleton to be utilised in oxidative metabolism
107
Which two pathways facilitate the removal of nitrogen (amino group) from amino acids?
Transamination
| Deamination
108
What happens to the nitrogen removed from amino acids by transamination or deamination?
Incorporated into other compounds or excreted as urea
109
What is transamination?
The swapping of the amine group of an amino acid with the oxygen of a keto acid producing a different amino acid and keto acid
110
Most aminotransferase enzymes use ________________ to funnel the amino group to _____________
a-ketoglutarate
Glutamate
111
Aspartate aminotransferase uses ___________ to funnel the amino group to ______________
Oxaloacetate
Aspartate
112
All aminotransferases require which coenzyme for their function?
This is derived from...
Coenzyme pyridoxal phosphate
Vitamin B6
113
Alanine aminotransferase converts ______________ to ____________
Alanine
| Glutamate
114
Aspartate aminotransferase converts _____________ to ______________
Glutamate
| Aspartate
115
Plasma ALT and AST levels are measured routinely as part of...
Liver function test
116
Plasma AST and ALT levels will be particularly high in which sorts of conditions? Give an example.
Conditions with extensive cellular necrosis
Viral hepatitis
117
How does deamination work? Where does it mainly take place?
Liberates amino group as free ammonia
Liver and kidney
118
Why is it useful for deamination to largely take place in the liver and kidneys?
The urea cycle is immediately available to process the free ammonia produced
119
What happens to the ammonia produced in deamination?
Rapidly converted to ammonium ions at physiological pH
Converted to urea or directly excreted in urine
120
Name 3 enzymes involved in the deamination process?
Amino acid oxidases
Glutaminase
Glutamate dehydrogenase
121
State some properties of urea?
High nitrogen content
Non-toxic - chemically inert in humans
Extremely water soluble
122
How is most urea excreted from the body?
In urine via the kidneys
123
Where does the urea cycle take place in the body? Involving how many enzymes? How are these enzymes stimulated/repressed?
Liver
5
Depending on amount of protein in the diet - e.g. High protein diet with stimulate enzymes
124
What are the risk factors for refeeding syndrome? (3)
BMI less than 16
Weight loss over 15% in 3-6 months
10 days or more with little or no food
125
When does refeeding syndrome occur? What happens? How do you avoid this?
When nutritional support is given to severely malnourished patients
Urea cycle is down regulated and not able to cope with levels of ammonia resulting in toxicity
Refeeding at 5-10 kcal/kg/day and raise gradually within a week
126
What are symptoms of ammonia toxicity?
```
Vomiting
Lethargy
Mental retardation
Seizures
Coma
```
127
Ammonia toxicity can result from defects in the urea cycle. How are these defects managed?
With a low protein diet, amino acids in diet replaced with keto acids
128
Ammonia is readily diffusible and extremely toxic to which organ?
Blood levels need to be kept low at which range?
The brain
25-40 microM/L
129
What toxic effects can ammonia have? (4)
Can disrupt cerebral blood flow
Affect the ph (alkaline)
Alteration of the blood brain barrier
Interference with the TCA cycle
130
Ammonia is disposed and fed into the urea cycle using which 2 amino acids?
Glutamine
Alanine
131
How is glutamine used in the disposal of ammonia?
Ammonia combined with glutamate to form glutamine
Glutamine transported in blood to the liver or kidneys where it reforms glutamate and ammonia. Ammonia fed into the urea cycle. Excreted directly in urine.
132
Which enzymes catalyses the cleavage of glutamine to glutamate and ammonia in the liver/kidneys?
Glutaminase
133
How is alanine involved in the disposal of ammonia?
Ammonia is combined with pyruvate to form alanine. Alanine transported to the liver, where it reforms pyruvate by transamination. Amino group fed via glutamate into urea cycle. Pyruvate used to synthesise glucose.
134
Problems in amino acid metabolism are usually due to a loss of...
They represent a significant portion of _____________ ___________ disease
Enzyme activity
Paediatric genetic
135
Untreated problems in amino acid metabolism can lead to...
What is the treatment?
Intellectual impairment
Restricting specific amino acids in the diet
136
Name three conditions the heel prick test can be used to test for?
Cystic fibrosis
Sickle cell disease
Congenital hypothyroidism
137
What causes phenylketonuria? Is it an autosomal recessive or dominant disease? Affecting which chromosome?
Deficiency in phenylalanine hydroxylase
Autosomal recessive
Chromosome 12
138
What happens in phenylketonuria?
There is accumulation of phenylalanine in tissue, plasma and urine resulting in the presence of phenylketones in the urine
139
Phenylketonuria presents with which particular smell?
Musty smell of the urine
140
What is the treatment for phenylketonuria?
Strictly controlled low phenylalanine diet
141
Which foods should be avoided in phenylketonuria?
Artificial sweeteners
| High protein foods (e.g. Milk, Eggs, Meat)
142
What are some symptoms of PKU?
```
Severe intellectual disability
Developmental delay
Microcephaly
Seizures
Hypopigmentation
```
143
What is microcephaly?
Small head
144
What is the most common cause of homocystinuria? What does it result in?
Defect in cystathionine-B-synthase
A problem breaking down methionine
Resulting in excess homocystine excreted in urine
145
Homocystine is ___________ homocysteine
Oxidised
146
Homocystinuria particularly affects which parts of the body?
Connective tissue, muscles, CNS and CVS
147
Elevated plasma homocysteine is associated with...
Cardiovascular disease
148
What is the treatment for homocystinuria?
Low methionine diet
| Cysteine, vitamin B6, betaine, B12 and folate supplements
149
Which foods should be avoided in homocystinuria?
Milk, meats, fish, cheese, eggs
| Nuts, peanut butter
