Metabolism Flashcards
To cover most Metabolism you are required to know for ESA 1 I take no responsibility for any of the flashcards featured here...mistakes/shit happens.
1
Q
Which two main hormones do the follicular cells of the thyroid release?
A
T3 (triiodothyronine) and T4 (thyroxine)
2
Q
Which main hormone do the parafollicular cells of the thyroid release?
A
Calcitonin
3
Q
What is the anatomical position of the thyroid gland?
A
- Inferior to voice box
- Anterior to trachea
4
Q
What type of epithelia can be found in the thyroid follicles?
A
Simple cuboidal
5
Q
Briefly outline the production of thyroid hormones. (6 key points)
Hint: ATE ICE
A
- Active transport iodide into the cytosol
- Thyroglobulin synthesis by the follicular cells
- Exocytosis to release vesicle of thyroglobulin into lumen
- Iodination of tyrosine parts of thyroglobulin
- Coupling of T1 (MIT) and T2 (DIT)
- Endocytosis into follicular cytosol followed by cleavage to form mature T3/T4
6
Q
What are the thyroid hormones bound to when travelling in the blood? Why?
A
The thyroid hormones are bound to thyroxine-binding globulin (TBG) as they are hydrophobic
7
Q
List the main actions of thyroid hormones?
A
- Increase BMR and temperature
- Increase normal growth/development - heart muscle + bone mineralisation etc.
- Ovulation
- Increase protein synthesis and metabolism
8
Q
How can T4 be converted to T3?
A
Cleavage of the 5’ iodide on the T4
9
Q
Which hormone controls the release of thyroid hormones and where is it released from?
A
Thyroid stimulating hormone (TSH) which is released from the anterior pituitary
10
Q
Which hormone controls the release of TSH and where is it secreted from?
A
Thyroid releasing hormone (TRH) is released from the hypothalamus and acts on thyrotrophs in the anterior pituitary
11
Q
Why does TRH travel in blood through the hypophyseal portal vein?
A
- Less hormone needed
- Faster response
12
Q
What is the autoimmune cause of Grave disease and therefore main cause of hyperthyroidism?
A
Formation of an antibody that stimulates TSH receptors on the thyroid producing excess T3/T4
13
Q
Name 3 other things that can be other causes of hyperthyroidism?
A
- Ectopic thyroid
- Excessive therapy of hypothyroidism
- Excessive treatment of other conditions with drugs - amiodarone
14
Q
What are the main symptoms of Grave’s disease?
A
- Exopthalmos
- Osteoporosis (due to excessive bone turnover)
- Weight Loss
- Heat intolerance
- Intestinal hypermotility
15
Q
What is the main treatment for Grave’s disease and how does it work?
A
- Carbimazole which works by preventing the iodination of thyroglobulin.
- Thyroid removal
16
Q
What are the two main autoimmune causes of Hashimoto’s disease?
A
- Antibody blocks a TSH receptor
- Destruction of follicles
17
Q
What can be other causes of hypothyroidism?
A
- Iodine deficiency (uncommon)
- Radiation
18
Q
What are the main symptoms of hypothyroidism?
A
- Weight gain
- Tiredness
- Cold intolerance
- Alopecia
- Decreased BMR
19
Q
What is the main treatment for hypothyroidism?
A
Oral thyroxine
20
Q
What does the parathyroid gland release and what does this control?
A
Parathyroid hormone which controls the level of calcium in the blood and in bones.
21
Q
What are the four main functions of active calcium?
A
- Muscle contraction
- Nervous conduction
- Enzyme activation
- Hormonal secretion
22
Q
In the blood which three ways can calcium be found?
A
- Free biologically active
- Bound to anionic sites on albumin
- Forming complexes with anions like citrate
23
Q
In what way are calcium and phosphate linked together?
A
Together they form calcium hydroxyapatite crystals which are minerals in bone
24
Q
What are the symptoms of hypocalcaemia? How are they caused?
A
- Convulsions
- Arrythmia
- Tetany (involuntary muscle contraction)
- Paraesthesia (tingling)
Due to low calcium at neuromuscular junctions which leads to easier depolarisation
25
What are the symptoms of hypercalcaemia?
Stoans, moans and groans:
- Kidney stones (renal calculi)
- Depression and tiredness
- Constipation and dehydration
26
What are the three hormones responsible for control of calcium levels?
- Parathyroid hormone
- Calcitriol
- Calcitonin (less important)
27
What would an increase in the level of PTH and calcitriol result in?
An increased level of serum calcium
28
How is calcitriol formed? (3 stages)
- Vitamin D absorbed in skin/gut
- Hydroxylation of the vitamin D in the liver to form calciferol as it has a longer half life
- Finally, calciferol is converted to calcitriol by hydroxylation in the kidney
29
What hormone regulates the formation of calcitriol?
Parathyroid hormone (PTH)
30
How are parathyroid hormone levels regulated by calcium?
- Chief cells have G-protein calcium receptors which when calcium levels are high are stimulated
- Causes the production of phospholipase C (PLC)
- PLC causes the inhibition of adenylate cyclase which reduces cAMP and PTH
31
What is Parathyroid releasing peptide (PTHrP) produced from?
Tumours
32
What does PTHrP do? From this, what could it be expected to do but doesn't?
It has similar effects to PTH as it:
- increases calcium release from bone
- decreased renal calcium excretion
- decreased renal phosphate reabsorption
Therefore, it may be expected to increase renal C-1 hydroxylase activity, like PTH, but it doesn't so has no effect on calicitriol concentration.
33
If there is too much PTHrP what can occur?
Humeral hypercalcaemia of malignancy
34
If the calcium level is low, what does the PTH do in the kidney?
Calcium reabsorption in the distal covoluted tubule of the kidney
35
If the calcium level is high what does the kidney do to phosphate? Why?
Phosphate is removed from circulation by the proximal tubule of the kidney to prevent the formation of calcium stones.
36
What is the outermost layer of the cortex called and what does it release?
Zona Glomerulosa which releases mineralcorticoids
37
What is the middle layer of the cortex called and what does it release?
Zona fasiculata which releases glucocorticoids
38
What is the innermost layer of the cortex called and what does it release?
Zona reticularis which releases androgens (and some glucocorticoids)
39
How is cortisol transported?
In the blood bound to proteins
40
What does an increase in cortisol production result in?
- Increase in gluconeogenesis and glycogenolysis
- Muscle proteolysis increases
- Lipolysis increases (lipogenesis increases at very high levels)
- Decreased immune system
41
Which clinical condition can be identified by a increased level of cortisol and ACTH caused by pituitary adenoma?
Cushings disease
42
Which clinical condition can be identified by a decreased level of cortisol due to adrenal adenoma?
Addisons disease
43
What is the difference between Cushings syndrome and disease?
Cushings syndrome relates to an elevated level of cortisol detected whereas Cushings disease relates to a tumour in the pituitary resulting in the elevated cortisol
44
What does a derease in cortisol production result in?
- Muscle weakness
- Hypotension
- Hypoglycaemia
45
What group of chemicals does the adrenal medulla produce? Which cells are they stored in?
Catecholamines stored in medullary cells
46
What type of hormone is cortisol and how is it transported?
Steroid hormone which is lipophillic and has to be bound to protein and transported in blood
47
Where is ACTH released from?
Anterior pituitary
48
What are the two main roles of ACTH?
- Activate cholesterol esterase - creating more free cholesterol
- Stimulate steps in the conversion of cholesterol to cortisol
49
What is the function of aldosterone?
Stimulates Na+ reabsorption
50
Briefly describe how adrenaline is formed
- Dopamine turned into noradrenaline
| - Noradrenaline methylated creating adrenaline
51
What effects on the body does an increased adrenaline level have on the body?
- Increased cardiac output
- Increased alertness
- Increased glycogenolysis
- Increased lipolysis
52
List 4 clinical consequences of too much adrenaline
- Hypertension
- Sweating
- Anxiety
- Glucose intolerance
53
How does adrenaline bind to cells?
Binds to adenoreceptors on the outside of cells then uses a secondary messenger system
54
How does cortisol bind to cells?
Crosses plasma membrane and binds to cytoplasmic receptors causing some genes to be transcribed
55
How does ACTH bind to cells?
Binding to corticotrophin receptor on the fasiculata and reticularis then a secondary messenger system
56
Describe the steps in the creation of glycogen from glucose
1) Glucose to Glucose-6-Phosphate (hexokinase/glucokinase)
2) Glucose-6-P to Glucose-1-P (Phosphoglucomutase)
3) Glucose-1-P are polymerised (Braching enzyme and glycogen synthase)
57
How do you work out BMI?
Weight (kg) divided by height x height (m)
58
How is lactate produced?
By reacting NADH, pyruvate and H+ together
59
How is pyruvate kinase activated?
Dephosphorylation
60
How much energy does each food group provide?
Lipid - 37000 kj/kg
Alcohol - 29000 kj/kg
Protein - 17000 kj/kg
Carbohydrates - 17000 kj/kg
61
Outline the process of oxidative phosphorylation
- Reduced coenzymes are reoxidised
- Electrons pass along the ETC until they are accepted by O2 at end
- Energy from electrons drive H+ across membrane
- Generation of a PMF
- H+ renter through ATP synthase molecule causing the production of ATP
62
What are the anabolic roles of the TCA cycle?
Provides precursors for the synthesis of amino acids, fatty acids and glucose
63
What are the catabolic roles of the TCA cycle?
Produce NADH, FAD2H, GTP and CO2
64
What are the main cellular processes that use energy?
- Biosynthetic work
- Osmotic work
- Mechanical work
- Electrical work
65
What are the three irreversible steps of glycolysis?
- Glucose to Glucose 6 phosphate (Hexokinase/glucokinase)
- Fructose-1-Phosphate to Fructose-1,6-Bisphosphate (Phosphofructokinase)
- Phosphoenolpyruvate to pyruvate (pyruvate kinase)
66
What are the three types of daily energy expenditure?
- Basal metabolic rate
- Diet induced thermogenesis
- Voluntary physical activity
67
What enzyme converts fructose to fructose-1-phosphate?
Fructokinase
68
What enzyme converts fructose-1-phosphate to GALP?
Aldolase
69
What enzyme converts pyruvate to lactate?
Lactate dehydrogenase
70
What factors affect the basal metabolic rate?
- Gender
- Temperature
- Endocrine status
- Weight (surface area)
71
What is the effect of dinitrophenol (DNP) on oxidative phosphorylation?
It increases the permeability to H+ ions which leads to the uncoupling of electron transport from ATP synthesis
72
What is the function of brown adipose tissue?
It is a naturally occuring uncoupling protein which produces heat through non-shivering thermogenesis - allows H+ back into mitrochondria without passing through normal channels
73
What is the purpose of the pentose phosphate pathway?
- Provide NADPH
| - Synthesise 5 carbon sugars for DNA creation (pentose sugars)
74
Where does the link reaction occur?
Mitrochondrial matrix
75
Where is glycogen stored?
Muscle and liver
76
Which enzyme regulates glycogen degradation?
Glycogen phosphorylase
77
Which enzyme regulates glycogen synthesis?
Glycogen synthase
78
Which enzyme regulates the TCA cycle and what activates/inhibits it?
Isocitrate dehydrogenase - activated by ADP and inhibited by NADH
79
Which organs remove lactate from the blood?
Heart and liver
80
Which tissues have an absolute requirement for glucose?
- Blood cells (Red and white)
- Lens of the eye
- Kidney medulla
81
Why are TAGs more efficient than glycogen?
- Hydrophobic so can be packed anhydrously
| - More reduced so yields more when oxidised
82
Why can't the human body digest cellulose?
The human body cannot break the Beta 1-4 linkages in the polysaccharide.
83
Why is glycolysis done in so many steps?
- Easier in small reactions
- Can be controlled
- Efficient energy conservation
- Production of useful intermediates
84
Why are there two enzymes for breaking down glycogen? (Glycogen phosphorylase and debranching enzyme)
Glycogen phosphorylase breaks alpha 1-4 linkages whereas debranching enzyme breaks the alpha 1-6
85
What is the approximate energy expenditure for a 70kg man?
12,000 kj
86
What is the approximate energy expenditure for a 58kg female?
9,500 kj
87
Define obesity
Excess body fat has accumulated to the extent that it may have an adverse effect on health (BMI > 30), leading to reduced life expectancy and/or increased health problems.
88
Define homeostasis
Homeostasis is the maintenance of a stable internal environment in a dynamic equilibrium.
89
What are the main features of control systems in the body?
- Communication
- Control centre
- Effector
- Receptor
90
Which enzyme catalyses the creation and breakdown of creatine phosphate?
Creatine kinase
91
What is the minimum glucose requirement for an adult each day?
180g
92
Name two uses of NADPH
- Lipid synthesis (important in liver/adipose)
| - Used to prevent Heinz body formation in red blood cells
93
What are the 4 key differences between the two types of phosphorylation in ATP synthesis?
Subs Level - soluble enzymes, energy coupling is direct, can be anaerobic, minor for ATP synthesis.
Oxid - membrane associated complexes, energy coupling is indirect, MUST be aerobic, major for ATP synthesis.
94
What are the 4 main hydroxy-methyl-glutaric acid derivatives? What are they for?
- Ketone bodies are water soluble fuel
- Cholesterol for membrane and steroid hormone synthesis
- Cholesterol esters for cholesterol storage
- Bile salts for lipid digestion
95
What are the 4 fat soluble vitamins?
A, D, E and K
96
What three things are required to hydrolyse TAGs in the small intestine?
- Pancreatic lipase
- Bile salts
- Protein factor called colipase
97
When TAGs are hydrolysed what happens to the glycerol?
It enters the blood stream and is transported to the liver where it is metabolised
98
What are the three different ketone bodies?
- Acetoacetate
- Acetone
- β-hydroxybutyrate
99
How is acetone formed?
Spontaneous non-enzymatic decarboxylation of β-hydroxybutyrate and acetoacetate
100
How are β-hydroxybutyrate and acetoacetate formed?
Synthesised in the liver from Acetyl~CoA
101
What level of ketone bodies in the blood is regarded as pathological ketoacidosis?
>10mM
102
Why are ketone bodies able to be secreted in the urine? (ketonuria)
Water soluble
103
When does ketone body synthesis occur?
When glucose is low i.e. starvation
104
Which enzyme produces HMG-CoA from acetyl CoA?
HMG CoA Synthase
105
Which enzyme converts HMG CoA to acetoacetate?
HMG CoA Lyase
106
What other ketone body is β-hydroxybutyrate produced from?
Acetoacetate
107
How is the ketone body used as a fuel?
Converted to acetyl CoA
108
What ratio controls the rate of ketone body synthesis?
Insulin/glucagon ratio
109
What two things are required for ketone body synthesis to occur?
- Fatty acids to be available for oxidation in the liver following excessive lipolysis in adipose tissue
- The plasma insulin/glucagon ratio to be low, usually due to a fall in plasma insulin – this activates the lyase and inhibits the reductase
110
Describe the steps in the breakdown of glycogen.
- Glycogen is broken into smaller sections by glycogen phosphorylase and debranching enzyme to form glucose-1-phosphate
- Glucose-1-phosphate is converted to glucose-6-phosphate by phosphoglucomutase
- In the liver the glucose-6-phosphate is converted to glucose by glucose-6-phosphatase
111
What is the main difference between muscle and liver glycogen?
Liver glycogen is used by all the body whereas muscle glycogen is only used by muscles
112
Why is glucose produced from non-carbohydrate sources?
Allows production of glucose when carbs are absent.
113
What is the main site of gluconeogenesis?
Liver
114
Name four substrates that can be used in gluconeogenesis?
- Pyruvate
- Lactate
- Glycerol
- Non-essential amino acids
115
In gluconeogenesis how are the irreversible steps bypassed?
1) Pyruvate -> Phosphoenolpyruvate - pyruvate carboxylase and PEPCK
2) Frustose 1,6-bisphosphate -> Fructose 6-phosphate - fructose 1,6-bisphosphatase
3) Glucose 6-phosphate -> Glucose - glucose 6-phosphatase
116
What two enzymes control the rate of gluconeogenesis?
- Fructose-1,6-Bisphosphatase
| - PEPCK
117
What is the effect of glucagon on PEPCK and Fructose-1,6-Bisphosphatase?
Increases the rate of both of them
118
What is the effect of insulin on PEPCK and Fructose-1,6-Bisphosphatase?
Decreases the rate of both of them
119
How is glycerol (from dietary TAGs) stored?
- Enters the blood
- Transported in chylomicrons
- Stored as TAGs in adipose tissue
120
What is the name of the process that degrades fatty acids?
Beta oxidation
121
Describe the process of Beta oxidation of fatty acids
The pathway oxidises fatty acids by removing a C2 (acetate) each time it is cycled through
122
What three things does Beta oxidation require to function?
- Oxygen
- NAD+
- FAD
123
What is the main substance produced from the Beta oxidation of fatty acids
Acetyl CoA
124
Where does fatty acid synthesis occur?
Cytoplasm
125
What is needed for fatty acid synthesis occur?
- Fatty acid synthase complex
- ATP
- NADPH
- Protons
126
Describe the process of fatty acid synthesis
Fatty acids are built up in a sequence by adding C2 each time in the form of malonyl CoA (loss of CO2)
127
How is Malonyl CoA produced?
From acetyl CoA using the enyme acetyl~CoA carboxylase and biotin
128
What enzyme controls the rate of fatty acid synthesis?
Acetyl~CoA carboxylase
129
What regulates the acetyl~CoA carboxylase enzyme?
- Allosteric regulation - citrate activates and AMP inhibits
- Covalent modification - Insulin activates by promoting dephosphorylation, Glucagon & Adrenaline inhibit the enzyme by promoting phosphorylation
130
Why do amino acids need to be broken down?
In a typical western diet more protein is eaten than is needed to supply the essential amino acids so excess amino acids are broken down
131
What are amino acids that produce acetyl-CoA described as?
Ketogenic
132
What are amino acids that produce TCA intermediates and pyruvate described as?
Glucogenic
133
What does measuring Creatinine give an indication of?
The breakdown of creatine, if it is constant, gives an indication of muscle mass and renal function
134
How can ammonia be detoxified?
- Synthesis of N-compounds like glutamine
- Conversion to urea
Both can be excreted in urine
135
How can glutamine be synthesised?
From ammonia, glutamate and ATP using the enzyme glutamine synthetase
136
How can glutamine be excreted?
Glutamine is transported to the liver and kidney where it is hydrolysed by glutaminase releasing ammonia that is disposed of in the urine (kidney) and converted to urea (liver).
137
What two things do all defects of the urea cycle result in?
- Hyperammonaemia (high blood NH4+ concentration)
| - Accumulation and/or excretion of a particular urea cycle intermediate
138
What happens to urea in the liver?
Diffuses from the liver cells to the blood and is carried to the kidney where it is filtered and excreted in the urine.
139
Briefly describe transamination.
Use of transaminases to transfer NH2- group from molecules like alanine and aspartate
140
Which enzyme turns galactose to galactitiol?
Aldose reductase
141
Briefly describe deamination
D-amino acid oxidases break down D amino acids so they aren't use for protein synthesis (not normal for human body) produce NH3 and keto acids
142
What are pharmacokinetics?
What the body does to the drug
143
What are pharmacodynamics?
What the drug does to the body
144
What are the four components to pharmacokinetics? (ADME)
- Absorption
- Distribution
- Metabolism
- Elimination
145
What is the purpose of Phase 1 drug metabolism?
Exposes the reactive group by oxidation, reduction or hydrolysis
146
What is the purpose of Phase 2 drug metabolism?
Conjugation - addition of a water soluble group (Glucuronidation, sulphate conjugation, glutathione conjugation)
147
Name three metabolites that are more pharmacologically active than the original drug?
Phenobarbitone (from Primidone)
Norpethidine (from Pethidine)
Morphine (from Codeine)
148
What is the high energy cofactor needed for phase 2 of drug metabolism?
UDPGA - uridine diphosphate glucuronic acid
149
Give one drug that skips phase 1 metabolism and enters directly into phase 2?
Morphine
150
What enzyme system and cofactor does the phase 1 drug metabolism use?
Cytochrome P450 enzyme system and NADPH cofactor
151
Give two factors for variation in drug metabolism within the population
- Genetic factors (levels of enzymes etc)
| - Environmental factors (use of other drugs etc.)
152
What type of drug is paracetamol?
Antipyretic (suppresses fever)
153
At normal therapeutic levels how is paracetamol metabolised in the body?
It proceeds directly to phase 2 drug metabolism where it conjugates with glucuronide or sulphate
154
What occurs if a toxic dose of paracetamol is given?
It goes through a phase 1 pathway and forms the toxic product N-acetyl-p-benzo-quinone imine (NAPQI)
155
How does NAPQI damage the body?
- Toxic to hepatocytes
| - Undergoes Phase II conjugation with glutathione, which is an important anti-oxidant.
156
Where is the major site of alcohol metabolism?
Liver
157
Which enzyme converts alcohol to acetaldehyde? Which converts acetaldehyde to acetate?
```
Alcohol dehydrogenase (low specificity).
Aldehyde dehydrogenase.
```
158
What converts acetaldehyde to acetate?
Aldehyde dehydrogenase
159
What effect does excessive alcohol consumption have on the body?
- Low NAD+
- High Acetyl CoA
- Decrease in liver function (due to cell damage from toxic acetaldehyde)
- Effect on GI tract (impaired absorption of vitamins and minerals)
160
What problems does a high amount of acetyl CoA in excessive alcohol consumption cause?
- Production of ketone bodies - high blood acidity
| - Production of fatty acids however not enough lipoproteins to move it causing fatty liver development
161
What problems does a low NAD+ in excessive alcohol consumption cause?
- Build up of lactate as NAD+ used for conversion from pyruvate to lactate.
- Reduces kidneys ability to get rid of uric acid - you get urate crystal and gout
- Gluconeogenesis can't be activated
162
What drug can be given as a treatment for excessive alcohol consumption? How does it work?
Disulfiram which works by inhibiting the enzyme aldehyde dehydrogenase causing the build up of acetaldehyde and therefore hangover symptoms
163
What level of blood glucose classifies a patient as hypoglycaemic?
<3.0mM
164
What level of blood glucose classifies a patient as hyperglycaemic?
>7.0mM
165
Give three acute effects of hypoglycaemia (note: there are a lot more)
- Trembling
- Sweating
- Palpatations
166
Give three acute effects of hyperglycaemia (note: there are a lot more)
- Polydipsia
- Polyuria
- Weight loss
167
Give four effects of insulin?
- Increases glucose uptake and utilisation by muscle and adipose tissue
- Promotes storage of glucose as glycogen in the liver and muscle
- Promotes lipogenesis and storage of fatty acids as triacylglycerols in adipose tissues
- Promotes amino acid uptake and protein synthesis in liver and muscle
168
Give three effects of glucagon?
- Gluconeogenesis to maintain supplies of glucose for the brain
- Glycogenolysis in the liver to maintain blood glucose for glucose-dependant tissues
- Lipolysis in adipose tissue to provide fatty acids for use by tissues
169
What is a reaction described as if the energy release is greater than the input?
Exergonic
170
How can you obtain a rough estimate of BMR?
Weight (kg) x 100
171
Name three things that can increase the BMR.
- Pregnancy
- Lactation
- Thyroid hormones
172
What are clinicians increasingly using as opposed to BMI to give more accurate measure of risk of CV disease and obesity?
Waist to hip ratio
173
Above what core temperature is considered to clinically be hyperthermia?
38 degrees celsius
174
Below what core temperature is considered to clinically be hypothermia?
35 degrees celsius
175
What is the importance of DHAP in glycolysis?
Synthesis of TAGs in liver and adipose for storage
176
What is the function of superoxide dismutase (SOD)?
Turns reactive oxygen species into hydrogen peroxide
177
What activates uncoupling proteins in brown adipose tissue?
Noradrenaline
178
Name three defences against ROS?
- Glutathione
- NADPH
- Catalase (conversion from H2O2 to H2O)
179
Which is the most dense lipoprotein? What is its function?
HDL which transports cholesterol from tissues back to liver for disposal
180
Which is the least dense lipoprotein? What is its function?
Chylomicron which transports TAGs from intestine to adipose tissue
181
What is the function of LCAT?
Restores stability of lipoproteins by converting surface lipids to core lipids (cholesterol to cholesterol esters
182
What is the function of LDLs?
Take cholesterol from liver to tissues
183
What enzyme do neutrophils and monocytes use to cause an oxidative burst?
NADPH Oxidase
184
What does the secretion of ACTH from the anterior pituitary lead to the release of?
Cortisol from the adrenals
185
What is appetite controlled by?
Arcuate Nucleus in the hypothalamus.
186
What nerve do the secondary neurones use to co-ordinate a response to appetite and metabolism?
Vagus nerve
187
In the stimulation of appetite, what neuropeptide do stimulatory primary neurones release?
Agouti related peptide (AgRP) and Neuropeptide Y
188
In the inhibition of appetite, what polypeptide do inhibitory primary neurones release?
Pro-opiomelanocortin (POMC)
189
What 3 things (important in appetite) can the polypetide prohormone POMC be enzymatically cleaved to produce?
- ACTH (Adrenocorticotrophin Hormone)
- α-MSH (α-Melanocyte stimulating hormone)
- β-endorphin
190
What does α-MSH act on to suppress appetite?
Melanocortin 4 receptor
191
What polypeptide is released when the stomach is full?
POMC
192
What polypeptide/hormone is released when the stomach is empty? Which neurone does it stimulate?
Ghrelin stimulates primary stimulatory neurone
193
What is the effect of increased PYY release? How is it released?
Stretching of the small intestine leads to PYY secretion which suppresses hunger.
194
Where is Leptin released from and what is it's function?
Released from adipocytes to suppress appetite
195
What is the effect of insulin on appetite?
Suppresses it
196
What are the two effects of Amylin release?
- Suppresses appetite and glucagon secretion
| - Slows gastric emptying
197
Which neurone do both insulin, leptin and PYY inhibit?
The primary stimulatory neurone
198
Which neurone do leptin and insulin stimulate?
The primary inhibitory neurone.
199
Where are amylin and insulin released from?
β-cells
200
Why is oxygen required for any step beyond glycolysis?
NAD+ needs to be reformed so the pyruvate is used to produce lactate
201
How are TAGs from chylomicrons and VLDLs released into tissues?
The endothelial cells of capillaries have lipase attached to their cell membrane. Chylomicrons and VLDLs bind to these enzymes and the TAGs are cleaved into fatty acids and glycerol. The FA enters the tissue and the glycerol remains in circulation.
202
How is cholesterol released from LDLs?
Cells have LDL receptors on their cell membrane which binds to the ApoB100 apoprotein. The LDL-receptor complex is taken into the cell. Lysosomes digest the lipoprotein, releasing cholesterol and breaking down cholesterol esters into cholesterol and FA.
203
How does insulin secretion increase during pregnancy?
Pancreatic B-cells undergo hypertrophy and hyperplasia, they become more sensitive to glucose by the action of oestrogen and progesterone.
204
Define endergonic.
An endergonic reaction has a higher energy input than the amount of energy released. An exergonic reaction has a higher amount of energy released than the energy input.
205
Define feedback.
Feedback is a mechanism by which the output of the system has an effect on the control system
206
Define metabolic syndrome.
A pattern of symptoms found in obese adults. It's existence is disputed. Symptoms are:
- insulin resistance
- dyslipidaemia
- impaired glucose tolerance
207
Define metabolism.
The processes which derive energy and raw materials from the diet and use them to support repair, growth and activity of tissues.
208
Describe how ammonium ions generated by deamination are disposed of.
1) Used to synthesise glutamine from glutamate
2) Glutamine can either directly release the ammonium ions at the kidneys (becoming glutamate)
Or
3) Transport it to the liver where it is used to synthesise urea in the ornithine cycle.
209
Describe how cholesterol is derived and used in the body.
Cholesterol can be derived from the diet but can also be synthesised in the diet. It can be used to make cholesterol ester by esterification with a FA. It is a HMA acid derivative.
210
Describe how energy is used in a 100m sprint.
1) ATP and creatine phosphate already present in muscle cells is used up.
2) Muscle glycogen is broken down to supply glucose-6-phosphate which then undergoes anaerobic respiration to supply more ATP.
211
Describe how fuel stores are used in a 1500m race.
1) Initial sprint - ATP and creatine phosphate are used up.
2) Middle phase - aerobic respiration of G-6-P from muscle glycogen takes place, some fat is aerobically respired.
3) Final sprint - anaerobic respiration of G-6-P from muscle glycogen takes place.
212
Where does Phase 1 of drug metabolism occur?
Mainly in microsomes in hepatocytes, but also in the GI tract, kidneys, lungs and blood plasma.
213
Describe stage 1 of carbohydrate metabolism.
Enzymes are secreted into the GI tract - amylase (from saliva and pancreas), lactase and isomaltase. Glycosidic bonds in polysaccharides are broken to form monosaccharides. These are actively transported into the intestinal epithelial cells and then into the blood and from the blood to tissues via GLUT receptors.
214
Describe the action of growth hormone on cells.
Growth hormone does not act directly on cells. It is converted to IGF-1 in the liver which acts on cells, usually promoting anabolism.
215
How does ghrelin control appetite?
It stimulates appetite by activating the primary stimulatory neurone.
216
How does insulin control appetite?
Suppresses appetite by both inhibiting primary stimulatory neurones and stimulating primary inhibitory neurones. (It's less significant than leptin.)
217
How does leptin control appetite?
Suppresses appetite by both inhibiting primary stimulatory neurones and stimulating primary inhibitory neurones.
218
How does PYY control appetite?
It suppresses appetite by inhibiting primary stimulatory neurones.
219
Describe the activation of FAs in stage 2 of FA metabolism.
FAs must be activated to undergo B-oxidation. This is done by linking the FA to CoA, forming acyl-CoA. This is catalysed by fatty acyl-CoA synthase.
220
Describe the blood supply to the thyroid gland.
The thyroid gland has a very good blood supply because it's an endocrine gland. It's supplied by the superior and inferior thyroid arteries and the superior, middle and inferior thyroid veins.
221
Describe the cellular defences against superoxide radicals.
The enzyme SOD converts superoxide radicals to H2O2. However, H2O2 is also a reactive oxygen species, so it is converted to H2O and O2 by catalase.
222
Describe the first stage of lipid metabolism.
In the small intestine the lipid is digested by lipases, secreted by the pancreas, into FAs and glycerol which are then absorbed into the intestinal epithelial cells.
223
Describe the general structure of a lipoprotein molecule.
A lipoprotein molecule consists of aggregates of lipid molecules contained within a micelle made up of phospholipids, apoproteins (ApoA to ApoH) and cholesterol. There are several classes of lipoprotein.
224
Describe the histological structure of the thyroid gland.
The thyroid gland is arranged into follicles. Each follicle is lined by follicular cells (simple cuboidal) and has a lumen filled with colloid. Between the follicles there is CT which contains parafollicular cells.
225
Describe the large-scale structure of the thyroid gland.
The thyroid has 2 lobes connected by as isthmus. Normally about 2-3cm across and has a very good blood supply.
226
Describe the process of alcohol metabolism.
Alcohol is first converted to acetaldehyde by the enzyme alcohol dehydrogenase (this can also be done by a CYP enzyme). Acetaldehyde is then quickly converted to acetate by aldehyde dehydrogenase (which has a very low Km for acetaldehyde). Acetate is then linked with CoA to form acetyl CoA. Both the alcohol -> acetaldehyde and acetaldehyde -> acetate reactions reduce NAD+ to NADH
227
Describe the process of deamination.
Deamination removes the NH2 group from an amino acid, forming ammonia, NH3. The ammonia is then converted to the ammonium ion, NH4. The ammonium ions are removed by the synthesis of glutamate or by the urea cycle.
228
Describe the process of FA synthesis.
FAs are synthesised by a series of reactions in the cytoplasm that add 2-carbon units to the carbon chain from malonyl-CoA. These reactions require large amounts of NADPH and ATP. Malonyl-CoA is produced from acetyl-CoA by the enzyme acetyl-CoA carboxylase. Acetyl-CoA carboxylase is the enzyme that regulates FA synthesis.
229
What is the difference between glycogenolysis in muscle and liver glycogen?
In muscle the glucose-6-phosphate is NOT converted to glucose. In the liver the glucose-6-phosphate is converted to glucose.
230
Describe the role of glutathione and NADPH in cellular defence against reactive oxygen species.
Glutathione has an -SH group which can donate it's H atom to ROS, thus acting as a reducing agent. It then becomes it's oxidised form, glutathione disulfide. NADPH can reduce glutathione, regenerating glutathione that can be used to reduce more ROS.
231
Describe B-oxidation
A series of reactions that each remove a 2-carbon unit (acetate) from the FA and produce 1 NADH and 1 FAD2H. The 2-carbon units are linked with CoA to form acetyl-CoA. These reactions continue until there are only 2 carbon atoms left.
232
Describe how creatine phosphate is used to supply energy.
Creatine phosphate is formed from creatine when there are high levels of ATP present. When levels of ATP are low, the reverse reaction occurs. In this way creatine phosphate acts as an energy store and can sustain several seconds of activity in a muscle cell.
Creatine + ATP Creatine phosphate + ADP.
233
Does gestational diabetes cause problems for the mother or the foetus?
Both
234
Explain re-feeding syndrome.
When a person is fed a high-protein diet immediately after prolonged starvation. During prolonged starvation the activity of the urea cycle decreases because less protein is being catabolised, but when the person is fed a high-protein diet there's a sudden influx of protein resulting in a lot of ammonia being produced when the amino acids are catabolised. The urea cycle doesn't have a high enough activity to process all of the urea and the excess ammonia can cause death.
235
Explain the concept of a HbA1c test and it's use clinically.
A HbA1c test measures the proportion of HbA1c present in the blood. This is related to the average blood glucose concentration over the last 3 months (the lifespan of a rbc is 3 months). Clinically, a HbA1c test is used to access how well a diabetic is controlling their blood glucose. A measurement of over 10% HbA1c indicates poorly controlled diabetes.
236
Explain the concept of nitrogen balance.
Nitrogen enters the body in the diet and is excreted in the urine. If the amount if nitrogen in equals the amount of nitrogen out, the individual is said to have zero nitrogen balance. If the nitrogen out > nitrogen in the individual is said to have negative nitrogen balance. If nitrogen out < nitrogen in the individual is said to have positive negative feedback.
237
Explain the effects of excessive alcohol consumption on the body.
Depleted NAD+/NADH ratio means there's inadequate NAD+ for FA oxidation, conversion of lactate to pyruvate and glycerol metabolism, causing accumulation of lactate in the blood and fasting hypoglycaemia. The increased level of acetyl-CoA and NADH causes FA production, which can't be transported out of the liver, giving fatty liver. Ketone bodies may be produced which can cause ketoacidosis.
238
Explain the purpose and process of the pentose phosphate pathway.
The PPP has 2 stages.
1) Glucose-6-phosphate is converted to a 5-carbon sugar and reduces NADP to NADPH.
2) 3 5-carbon sugars are converted to 2 fructose-6-phosphate molecules and glyceraldehyde-3-phosphate which can both re-enter glycolysis.
The PPP creates 5-carbon sugars for nucleotide synthesis and also generates NADPH.
239
Explain the role of lactate with regard to glycolysis.
Lactate is created during periods of anaerobic respiration because the conversion of lactate to pyruvate regenerates NAD+ which is needed for glycolysis to occur but in anaerobic conditions it cannot be regenerated as part of oxidative phosphorylation. The reaction of pyruvate lactate is catalysed by lactate dehydrogenase.
240
What is an essential amino acid?
An aa which can't be synthesised by the body and must be taken in through the diet.
241
Why is urea a suitable molecule for the transport and excretion of nitrogen?
Urea is highly soluble, inert, non-toxic and has a high hydrogen content.
242
What does growth hormone (generally) promote?
Anabolism.
243
Give 2 examples of biological rhythms.
The concentration of cortisol in the blood throughout the day (circadian rhythm) and the menstrual cycle.
244
Give 4 functions of metabolism.
- To produce energy in the form of ATP
- To supply building block molecules for synthesis of larger cell components
- To produce precursor molecules for interconversion of building block molecules
- To create reducing power in the form of NADH, FAD2H, NADPH etc.
245
Give 5 benefits of exercise.
```
Better balance of lean tissue and fat in the body.
Lower blood lipids.
Lower blood pressure.
Increased glucose tolerance.
Increased muscle sensitivity to insulin.
```
246
Example of a drug which is an oxidising agent.
The antimalarial primaquine.
247
Give a hormone which is secreted from the zona reticularis.
Testosterone.
248
Give an example of a mineralocorticoid.
Aldosterone
249
Give examples of antioxidants (other than glutathione) that provide defence against ROS
Vitamins A, C, E, flavenoids such as polyphenols and carotene, minerals such as selenium and zinc.
250
Give examples of diseases linked to oxidative stress
Cancer, CVD, emphysema, pancreatitis, Crohn's, type 1 diabetes, Alzheimer's.
251
Give examples of inducing and inhibiting agents for drug metabolism.
Inducing agents include alcohol, barbiturates and nicotine. Inhibiting agents include grapefruit and cranberry juice.
252
How and where is lactate dealt with?
Lactate is utilised either by conversion back into pyruvate for the Kreb's cycle at the heart or used in gluconeogenesis at the liver. Lactate is also disposed of at the kidney by excretion in the urine.
253
How are hydroxyl radicals produced?
By ionising radiation.
254
How are the B-cells of the pancreas adapted for insulin production?
Extensive RER, well defined Golgi bodies, many mitochondria and well defined microtubules and microfilaments.
255
How can ROS be used for the benefit of the body?
Certain immune cells such as neutrophils and macrophages can rapidly produce ROS in an oxidative burst, which kills pathogens as well as the immune cell itself. The ROS are produced by the enzyme NADPH oxidase.
256
How do adrenaline levels change during a marathon? What effect does this have on insulin levels?
Adrenaline concentration increases rapidly. This decreases insulin concentration.
257
How do blood glucagon concentrations change during a marathon?
Blood glucagon concentration increases steadily.
258
What are the metabolic consequences of a decrease in insulin concentrations?
Reduces the amount of energy being stored and increases blood glucose concentration.
259
How do carrier proteins affect the properties of the hormone they bind to?
They increase solubility and half-life when the hormone is bound.
260
How do cortisol levels change during a marathon? What are the metabolic consequences of this?
Cortisol levels rise slowly throughout the marathon. This mobilises fat stores and stimulates gluconeogenesis.
261
How do growth hormone levels change during a marathon? What is the metabolic consequence of this change?
They increase rapidly, which stimulates mobilisation of fat stores.
262
How do hydroxyl radicals damage cells?
Very damaging to cell membranes and can cause the cell to lyse.
263
How do you estimate the numerical value of diet-induced thermogenesis?
It's about 10% of the energy content of the consumed food.
264
How can you estimate the numerical value of energy expended by voluntary activity?
If a person is sedentary, it's about 30% of BMR. If a person does moderate exercise, it's about 60% of BMR. If a person does heavy exercise, it's equal to BMR.
265
How does acyl-CoA enter the mitochondria?
Acyl-CoA (activated FA) can't enter mitochondria directly because they can't pass through the inner membrane. Acyl-CoA is transported across the inner membrane via the carnitine shuttle. Acyl-CoA is converted to acyl carnitine which crosses the membrane. This reaction is reversible and inhibited by malonyl-CoA, which is involved in FA synthesis.
266
How is 1,3-BPG created and what else can it be used for?
It is created by step 6 of glycolysis. It can be converted to 2,3-BPG which is the molecule that binds to Hb and decreases it's affinity for oxygen, giving more efficient oxygen transport.
267
How is cholesterol supply matched to demand?
The expression of LDL receptors on the cell surface membranes of cells is changed according to the concentration of cholesterol in the cell.
268
How is nitric oxide produced?
Nitric oxide is synthesised in the body by nitric oxide synthases, in particular nitric oxide synthase which is an enzyme involved in inflammation. It has an important role in bodily control mechanisms but is also a ROS.
269
List all of the hormones which feed back from the body to the primary neurones in the arcuate nucleus.
Ghrelin, PYY, leptin, insulin, amylin
270
List all of the hormones that act in the excitatory primary neurones of the arcuate nucleus.
Ghrelin, PYY, leptin, insulin
271
List all the hormones that act on the inhibitory primary neurones of the arcuate nucleus.
PYY, leptin, insulin
272
What effects do glucagon have on target tissues?
Increase glycogenolysis in the liver.
Increase lipolysis in adipose tissue.
Increase gluconeogenesis in the liver.
Increase ketone body synthesis in the liver.
273
List the major energy stores in an average 70kg man
TAGs: 15kg, glycogen: 0.4kg, protein: 6kg
274
Name 3 anti-insulin hormones secreted in high amounts during pregnancy.
Oestrogen, progesterone and hPL
275
List the 6 essential components of the diet.
Carbohydrate, protein, lipid, vitamins and minerals, fibre, water.
276
Outline how a high level of LDLs in the blood is thought to cause atherosclerosis.
The LDLs are oxidised, then phagocytosed by macrophages in artery walls. As macrophages phagocytose more and more LDLs they become foam cells. The buildup of foam cells forms a fatty streak, which then turns into an atheroma.
277
Outline the catabolism of amino acids.
The NH2 group is removed by transamination or deamination. The remaining carbon skeleton is converted to another molecule which depends on the type of amino acid. Ketongenic amino acids are converted to acetyl-CoA which is used to synthesise ketone bodies. Glucogenic amino acids can be converted to pyruvate, oxaloacetate, fumarole, a-ketoglutarate or succinate.
278
Outline the mechanism by which insulin secretion is controlled by the blood glucose concentration.
Increased glucose concentration in the blood causes increased concentration in the extracellular fluid.
Glucose is transported into the B-cell by GLUT2.
Increased glucose concentration increases ATP/ADP ratio.
Increased ATP/ADP ratio causes depolarisation of the cell surface membrane.
Depolarisation causes influx of calcium ions via voltage-gated calcium channels.
Influx of calcium ions causes exocytosis of insulin.
279
Outline the process of urea.
The urea cycle produces urea from ammonium ions. It occurs partly in the cytoplasm and partly in mitochondria. 5 enzymes are involved and there are several intermediates of the cycle. The cycle is not directly regulated but it's inducible, so if there is more ammonium the turnover of the cycle will increase and if the is less ammonium the turnover will decrease.
280
Outline the treatment for diabetic ketoacidosis.
Fluid replacement, insulin
281
What are the 4 classes of hormone?
- Polypeptide hormones - largest class of hormone, nearly all single chain polypeptides, varying in length, eg. insulin, glucagon, GH.
- Glycoprotein hormones - all glycoprotein hormones have 2 polypeptide chains with a carbohydrate side chain, eg. FSH
- Amino acid derivative hormones - derived from aas, eg. thyroid hormone, adrenaline.
- Steroid hormones - derived from cholesterol, 4 ring part remains, but the functional group changes, eg. testosterone, oestrogen and cortisol.
282
What are the 5 possible fates of nutrients?
```
Degradation to release energy.
Synthesis of cell components.
Storage.
Interconversion to other nutrients.
Excretion.
```
283
State the features of a control system which use hormones for communication.
Endocrine gland(s) to produce the hormone.
Transport of the hormone in the blood to the target cell.
Receptors for the hormone to bind to cause a response.
Inactivation of the hormone.
284
What 3 main metabolic changes occur during starvation?
The brain becomes able to use ketone bodies as fuel.
The kidney cortex begins to contribute to gluconeogenesis.
BMR falls to a lower level.
285
What are GLUT proteins and what is their function?
GLUT proteins are transport proteins that allow facilitated diffusion of monosaccharides from intestinal epithelial cells into the blood and facilitated diffusion from the blood into tissue cells. There are 5 GLUT proteins, some can be hormonally controlled eg. GLUT4 is inserted into the membrane in response to insulin.
286
What are hyperlipoproteinaemias?
High levels of one or more type of lipoprotein in the blood. They are caused by over-production or under-removal of lipoproteins. This can be due to defective enzymes, receptors or apoproteins.
287
What are superoxide radicals and how do they form?
Superoxide radicals (O2-) are a ROS. A superoxide radical is formed when an electron in the ETC doesn't reach the end because it drops out. The electron reacts with oxygen, forming the superoxide radical.
288
What are the 2 main things achieved by the metabolic changes that occur during pregnancy?
Higher levels of nutrients in the blood and increase in the amount of energy stores, particularly fats.
289
What are the 3 classes of lipids?
FA derivatives, hydroxy-methyl-glut auric acid derivatives, vitamins.
290
What are the 5 cell types of the anterior pituitary gland and what do they release?
```
Thyrotrophs release TSH
Corticotrophs release ACTH
Somatotrophs release GH
Gonadotrophs release LH and FSH
Lactotrophs release prolactin
```
291
What are the acute effects of hyperglycaemia?
Ketoacidosis, hyperosmolar non-ketotic syndrome.
292
What are the chronic effects of hyperglycaemia?
Microvascular effects include nephropathy (kidney damage), retinopathy (diabetic eye disease), neuropathy (damage to peripheral nerves) and diabetic feet (caused by nerve damage, poor circulation and infection). Macrovascular effects include higher risk of stroke and MI caused by poor circulation to the periphery.
293
What are the clinical consequences of hypothyroidism in newborn children?
Will cause cretinism if not treated within 3 weeks. Cretinism caused severe mental retardation, course features, decreased growth and decreased sexual development.
294
What are the clinical consequences of inadequate glycogen storage?
Hypoglycaemia some time after meals and low exercise tolerance.
295
What are the clinical consequences of too much glycogen storage?
Damage to muscle and liver due to the osmotic effect of glycogen.
296
What are the different types of communication that a biological control system may use?
Nervous, endocrine, paracrine (local hormones), autocrine (hormones released by the cell that will be affected)
297
What are the possible causes of hypercalcaemia?
Hyperparathyroidism due to an adenoma of the parathyroid gland, ectopic secretion of PTH or PTHrP (a molecule which mimics the action of PTH except for the stimulation of activation of vit D)
298
What are the possible causes of hypocalcaemia?
Accidental surgical removal of the parathyroid glands, renal failure, hypothyroidism (rare)
299
What are the target tissues of glucagon?
Mainly the liver.
300
What are the target tissues of insulin?
Mainly the liver, skeletal muscle and adipose tissue.
301
What are the target tissues of the thyroid hormones?
Virtually every tissue.
302
What components of the cell can ROS damage?
DNA, lipids in cell membranes, proteins.
303
What controls the synthesis and secretion of T3 and T4?
The hypothalamus produces and secretes TRH which acts upon the anterior pituitary gland and stimulates it to produce TSH. TSH acts on the thyroid gland and stimulates the production and secretion of thyroid hormone. TSH also stimulates growth of the thyroid gland itself. The secretion of TRH and TSH is controlled by negative feedback.
304
What do LDL receptors bind to?
ApoB100
305
What do the different types of neurone in the arcuate nucleus do?
Primary neurones sense the levels of glucose and FAs in the blood and respond to hormones. Excitatory primary neurones stimulate appetite and inhibitory primary neurones inhibit appetite.
Secondary neurones receive the input from primary neurones and co-ordinate a response via the vagus nerve.
306
What do the hormones secreted by the posterior pituitary gland do?
ADH is involved in the control of water reabsorption in the kidneys, oxytocin stimulates maternal behaviour and romantic behaviour.
307
What does the concept of Developmental Origin of Health and Disease (DOHaD) mean?
DOHaD states that birth weight is strongly linked to the incidence of adult disease eg. CHD, hypertension and type 2 diabetes incidence correlate with a low birth weight.
308
What effects do high energy signals have on metabolism?
They promote anabolic reactions and inhibit catabolic reactions because they signal that the cell has ample energy.
309
What effect do low energy signals have on metabolism?
They promote catabolic reactions and inhibit anabolic reactions because they signal that the cell has insufficient.
310
What effect does PTH have on bone.
It stimulates osteoblasts to release cytokines that promote osteoclasts differentiation and activity, which increases the reabsorption of bone and causes a rise in serum calcium levels.
311
What effect does PTH have on the kidneys?
It increases the amount of reabsorption of calcium in the kidneys so less is excreted. It also stimulate the conversion of vitamin D to it's active form, calciferol, in the kidneys.
312
What effect does vitamin D have on the gut?
Vitamin D stimulates the uptake of calcium from the diet in the gut.
313
What effect does vitamin D have on the kidneys?
It stimulates reabsorption of calcium in the kidneys.
314
What effect might renal failure have on serum calcium levels?
Renal failure could cause serum calcium levels to fall because of decreased calcium reabsorption.
315
What factors affect the magnitude of a target cell's response to a hormone?
The amount of hormone.
The amount of receptors for a hormone.
The affinity of receptors for the hormone.
The degree of amplification of the signal.
316
What happens after phase 2 of drug metabolism?
The water-soluble drug-conjugate complex is excreted in the urine.
317
What happens to remnants of VLDLs after they have offloaded TAGs at the target tissue?
They are removed by the liver or converted to other lipoprotein particles.
318
What happens to T4 at it's target tissues?
It's converted to T3 by removal of an iodine group.
319
What hormone inhibits the secretion of GH from the anterior pituitary gland?
Somatostatin.
320
What hormone promotes release of GH from the anterior pituitary gland and where is this hormone secreted from?
GHRH (growth hormone releasing hormone), secreted from the hypothalamus.
321
What hormones affect glycogenesis?
Insulin stimulates glycogenesis and glucagon inhibits it. (Insulin dephosphorylates the enzymes involved and glucagon phosphorylates the enzymes involved).
322
What hormones affect glycogenolysis?
Glucagon and adrenaline both stimulate glycogenolysis.
323
What is a biological rhythm?
A biological rhythm occurs when the set point of a control system is not fixed and varies according to time.
324
What is a circadian rhythm?
A circadian (or diurnal) rhythm is a biological rhythm that varies over a 24 hour timescale.
325
What is an adenoma?
A benign tumour of glandular tissue.
326
What is an apoprotein?
A protein found in the micelle of a lipoprotein. There are several different apoproteins and each class of lipoprotein has specific apoproteins. Apoproteins have structural roles and functional roles such as enzyme activation and recognising cell surface receptors.
327
What is creatinine?
| What is it's clinical significance?
Creatinine is the breakdown product of creatine and creatine phosphate. It's produced by a spontaneous reaction at a constant rate so normally the blood concentration is very stable. Creatinine excretion over 24 hours is proportional to muscle mass. If there is muscle wasting, blood creatinine concentration increases.
328
What is foetal programming? What theory is it a possilbe explanation for?
The idea that a foetus adapts to the conditions such as nutrient supply in utero and this is related to disease in adult life. Foetal programming is a possible explanation for DOHaD.
329
What is the most common cause of hyperthyroidism?
Grave's disease.
330
What is the most common cause of hypothyroidism?
Hashimoto's disease.
331
What is POMC a precursor for? What do these molecules do?
- ACTH = stimulates corticosteroid production and secretion
- a-MSH = inhibits appetite
- B-endorphin = part of the reward system and produces feelings of euphoria and tiredness.
332
What is the cytochrome P450 system?
An enzyme system that catalyses part 1 of drug metabolism. There are polymorphisms of enzymes in the cytochrome P450 systems in the human population.
333
What is the effect of aldosterone on the kidneys?
Acts on the distal tubules and collecting ducts of the kidneys to promote active reabsorption of sodium ions and secretion of potassium ions. The reabsorption of sodium ions causes water to be reabsorbed and thus blood pressure increases.
334
What is the effect of glucose on Hb?
Glucose glycosylates Hb, forming HbA1c
335
What is the enzyme that defends against hydroxyl radicals?
There isn't one
336
What is the first stage of the pentose phosphate pathway and which enzyme is it catalysed by?
Glucose-6-phosphate -> 5-carbon sugars, accompanied by the reaction of NADP -> NADPH.
Glucose-6-phosphate dehydrogenase.
337
What type of hormone do all three layers of the adrenal cortex produce?
Steroid hormone.
338
What is the general formula for carbohydrates?
(CH2O)n
339
What is the minor hormone involved in calcium metabolism, where is it secreted from and what does it do?
Calcitonin is secreted from the parafollicular cells in the thyroid gland and it lowers serum calcium levels.
340
What is the most common cause of excessive GH secretion?
A pituitary adenoma.
341
What is the most common cell type of the anterior pituitary gland?
Somatotrophs
342
What is the name for the covalent bond between monosaccharides and how is it formed?
Glycosidic bond, condensation reaction between OH and H groups, eliminating H2O
343
What is the name of the axis that controls section of cortisol?
HPA axis
344
What is the nett change in ATP during phase 2 of glycolysis?
4 molecules of ATP are made per glucose molecule during phase 2 by substrate level phosphorylation.
345
What is the nett change in ATP molecules for phase 1 of glycolysis?
2 molecules of ATP are used up per glucose molecule.
346
What is the normal blood concentration of ketone bodies?
1mM
347
What is the normal blood concentration of lactate and at what concentration does it begin to cause acidosis?
The normal blood concentration is 1mM.
| If the concentration is >5mM, it causes acidosis.
348
What is the normal concentration of calcium in the blood (total and free)?
Total: 2.2 to 2.5mM
Free: 1.0 to 1.3mM
349
What is the primary function of skeleton?
To buffer the level of calcium in the blood when it becomes low.
350
What is the priority of metabolism during exercise?
To supply the brain with glucose.
351
What is the purpose of the increased level of insulin during pregnancy?
To promote energy storage
352
What is the relationship between anabolism and catabolism?
Anabolism uses the energy and reducing power released by catabolism.
353
What is the role of pyruvate dehydrogenase?
Catalyses the conversion of pyruvate to acetyl-CoA. This is accompanied by the loss of CO2 so it is irreversible. The acetyl-CoA may then enter the Krebs cycle.
354
What is the role of the control centre in a biological control system?
To analyse the incoming signals from receptors and coordinate a response. The control centre also decides the 'set point' as a reference for whatever is being controlled.
355
What is the role of effectors in a biological control system?
To produce an effect when a signal from the control centre is received.
356
What is the role of the receptors in a biological control system?
To detect stimuli and relay the information to the control centre.
357
What is the route taken by chylomicrons to their target tissue and why is this route taken?
From the gut, they enter lacteals (small lymphatic vessels) and travel through the lymphatic system to the thoracic duct then into the left subclavian vein. This allows them to bypass the liver.
358
What is the second stage of the pentose phosphate pathway?
3 5-carbon sugars are converted to 2 fructose-6-phosphate molecules and 1 glyceraldehyde-3-phosphate molecule.
359
What parts of the body does PTH act on?
Bone and kidneys
360
What parts of the body does vitamin D (calcitriol) act on?
Bone, gut and kidneys
361
Where is the pituitary gland derived from?
The anterior pituitary gland is derived from gut tissue and the posterior pituitary gland is derived from nervous tissue.
362
What processes make up stage 2 of FA metabolism?
Activation of FA, transport of FA into mitochondria and B-oxidation
363
What stimulates glycogenolysis during a 1500m race?
Adrenaline
364
What stimulates the release of CRH from the hypothalamus?
Physical chemical or emotional stress
365
When are TAGs released from storage?
In stress ie. starvation, exercise or pregnancy and when the insulin/glucagon ratio is low
366
Where and how are HDLs synthesised?
HDLs are synthesised in tissues either from shells (nascent HDL) in the liver or from VLDL remnants. Both types take up cholesterol in the tissues and convert into mature HDL particles, which then transport the cholesterol to the liver.
367
Where are chylomicrons formed and what is their function?
Chylomicrons are formed in the epithelial cells which line the intestine. Their function is to transport TAGs (re-formed in the epithelial cells from absorbed FA and glycerol), and also cholesterol and lipid soluble vitamins from the intestine to tissues, especially adipose tissues.
368
Where are LDLs synthesised and what is their function?
LDLs are synthesised in the liver. Their function is to transport cholesterol synthesised in the liver to tissues.
369
Where are the hormones which stimulate the increase in energy stores during pregnancy secreted from?
Mainly the placenta, some from the ovaries.
370
Where does stage 1 of carbohydrate metabolism take place?
In the GI tract, is it extracellular.
371
Where is insulin produced?
In the B-cells of the islets of Langerhans in the pancreas.
372
Where is the pituitary gland found?
In the brain, inferior to the optic chasm and connected to the hypothalamus via the pituitary stalk.
373
Where is the body's biological clock and what is involved in 'setting it'?
The biological clock is found within the suprachiasmic nucleus in the hypothalamus. The hormone melatonin is involved in setting it. The time is kept up to date by detection of environmental factors called Zeitgebers.
374
Which 2 classes of lipoprotein transport mainly TAGs?
Chylomicrons and VLDLs
375
Which amino acid is adrenaline derived from?
Tyrosine
376
Which hormone controls the long term regulation of serum calcium, and which the short?
PTH controls the short term
| Vitamin D controls the long term
377
Which molecules cause appetite to be stimulated when they are detected at the secondary neurones?
Neuropeptide Y and AgRP
378
Which part of the adrenal gland is adrenaline secreted from?
The adrenal medulla
379
Why can a high concentration of ACTH cause increased pigmentation of some parts of the body?
ACTH contains within it's polypeptide sequence the sequence of a-MSH so ACTH can stimulate melanocytes to some extent, causing skin pigmentation.
380
Why can't fat stores be utilised during a 100m sprint?
Extra oxygen cannot be supplied to the muscles during a sprint and catabolism of fats (B-oxidation) requires oxygen.
381
Why can't pyruvate enter the TCA cycle directly?
It can't pass through the impermeable inner mitochondrial membrane, whereas acetyl-CoA can.
382
Why does cortisol have weak mineralocorticoid and androgen effects?
Because steroid receptors have sequence homologous in the binding regions of their steroid hormone receptors. This means mineralocorticoid and androgen receptors have a low affinity for cortisol and cortisol can bind to them
383
Why is carbohydrate essential for the diet?
It's needed to provide energy.
384
Why is fibre essential to the diet?
It's needed for healthy digestion.
385
Why is lipid essential to the diet?
It supplies energy and essential FA.
386
Why is protein essential to the diet?
Is supplies essential amino acids.
387
Why is there a higher blood glucose level in a pregnant woman?
Despite the higher insulin level, the high anti-insulin levels ensures blood glucose remains high. Also, appetite is stimulated so more carbohydrates are taken in from the diet.
388
Why is water essential to the diet?
It's needed to replace the water lost in sweat, breath, urine and faeces.
389
What is the reaction which converts pyruvate to acetyl-CoA?
Pyruvate + CoA + NAD+ ---> acetyl-CoA + CO2 + H+
