Randoms Flashcards
(251 cards)
1
Q
What condition uses the drug carbimazole for treatment?
A
treat hyperthyroidism
pro-drug and is converted to its active form methimazole by the body.
methimazole prevents the enzyme thyroid peroxidase from coupling and iodinating tyrosine residues on thyroglobulin therefore reducing the production of thyroid hormones T3 and T4
2
Q
can ROS damage proteins and result in protein glycosylation?
A
no-
glycosylation is a normal post- translational modification
3
Q
What is the term that describes abnormally shaped RBCs?
A
Poikilocytosis
4
Q
Glycerol released upon the hydrolysis of triacylglyercol can enter which pathway after additional reactions?
A
glycolysis -
after phosphorylation to glycerol phosphate and concession to dihydroxyacetone phosphate, glycerol can enter glycolysis.
5
Q
in which nucleus of the hypothalamus are the neurones that constitute as the biological clock located?
A
suprachiasmatic nucleus
6
Q
what are two endogenous sources of free radicals?
A
- ETC major source
- peroxidase enzymes
- nitric oxide synthase
- NADPH oxidase enzyme
7
Q
What is the correct sequence of lipoproteins in the order of most to least dense?
A
HDL> LDL> VLDL> chylomicrons
8
Q
What is the mode of action of spironolactone?
A
mineralocorticoid receptor antagonist
9
Q
what is the role of leutinizing hormone in men?
A
LH acts upon Leydig cells of the testis to control the production of testosterone
10
Q
what does the membrane bound enzyme thyroid peroxidase regulate?
A
- oxidation of iodide to iodine
- addition of iodine to tyrosine acceptor residues on thyroglobulin
- coupling of monoiodotyrosine and diiodotyrosine molecules within thyroglobulin
11
Q
the cause of pernicious anaemia?
A
auto-antibodies interfering with the production or function of intrinsic factor
intrinsic factor essential for the absorption of bit B12 in the ileum.
12
Q
name a carbohydrate that is a source of dietary fibre
A
cellulose
- others include lignin, pectin and gums
13
Q
What is the primary abnormality in patients presenting with diabetic ketoacidosis
A
absolute insulin deficiency leading to ketone production
14
Q
which endocrine gland secretes melatonin (hormone)?
A
Pineal glands
15
Q
What effect would a decrease in intracellular ATP conc have on the ATP sensitive K+ channels in pancreatic beta cells?
A
more K(ATP) channels would be in the open state
- these channels are inhibited by ATP
- fall in ATP will leave more channels open
- more K+ ions leave the cell through the channel so plasma membrane becomes hyperpolarised
- more - membrane potential makes cells less excitable
- prevent insulin release
16
Q
What is a treatment option for a patient with severe hereditary haemochromatosis
A
therapeutic phlebotomy to remove excess iron
17
Q
what is Hereditary haemochromatosis
A
autosomal recessive disorder of iron metabolism that results in toxic levels of iron accumulation
excess iron affect organ function by direct toxic effects
18
Q
which class of hormone does adrenaline fall under?
A
amine hormone
- synthesised from the amino acid tyrosine
19
Q
which disease results from excess growth hormone secretion occurring after puberty after the epiphyseal plates have closed?
A
Acromegaly
- anterior pituitary glad produces excess growth hormone after epiphyseal plate closure at puberty
20
Q
activation of which adrenergic receptor subtype mediates the effect of adrenaline and noradrenaline on the heart?
A
Beeta-1 adrenergic receptor
- through Gapha-s
21
Q
what is a symptom of hypocalcaemia
A
tetany
- muscle spasms
22
Q
what is the half life of thyroxine (T4) in plasma?
A
around 5-7 days
23
Q
what is the half life of T3?
A
around 1 day
24
Q
activation of which adrenergic receptor subtype mediates bronchodilator in the lungs?
A
Beta-2 adrenergic receptor
25
which breakdown product of haem is responsible for the yellow discolouration often seen around a bruise?
bilirubin
26
which type of diabetes shows markers for autoimmunity
type I diabetes mellitus
27
which hormone is released from the pancreas and supresses appetite?
amylin
28
what inhibits the release of iron from erythrocytes and macrophages?
hepcidin
- inhibits iron transport by binding to ferroportin located on the basolateral membrane of erythrocytes.
- inhibition of ferroportin by hepcidin prevents iron from being exported into the bloodstream thereby reducing dietary iron absorption
- iron release from macrophages is also reduced by hepcidin inhibition of ferroportin
29
A child has 'glycogen storage disease type 1). his abdomen is large and potuberant. why is his abdomen protuberant?
liver is enlarged due to glycogen accumulation
30
what is the desirable range for BMI?
18.5-24.9 kg/m2
31
what could be a treatment option for a patient with beta Thalassaemia?
red cell transfusion
- iron overload is a major cause of premature death in thalassaemias duet excessive absorption of dietary iron due to ineffective haematooiesis and the repeated blood transfusions required to treat the anaemia
32
when does the switch from fetal to adult haemoglobin occur?
around 3-6 months of age
33
what is measured by a direct Coombs test?
antibodies bound directly to the surface of RBCs
34
when is a direct Coombs test used?
- when immune- mediated haemolytic anaemia is suspected
| - test determines if antibodies or complement system factors have bound to RBCs surface antigens in vivo
35
What do the parafollicular cells within the thyroid gland secrete?
calcitonin
36
where is thyroid hormone synthesised?
synthesised in and released from the thyroid follicles
37
What are follicular cells filled with?
colloid
| - deposit of the protein thyroglobulin
38
What is present in a patient with Felty's syndrome?
RhA, splenomegaly, neutropenia
39
what produces the glycoprotein hormone erythropoietin?
interstitial fibroblasts in the kidney
40
what is a feature of anabolic pathways?
they involve the synthesis of larger molecules from intermediary metabolites
41
where is thyroid stimulating hormone released from?
anterior pituitary gland
42
what are the examples of a ketone body?
- acetone
- acetoacetate
- beta- hydroxybutyrate
43
what are the two most significant factors underlying the aetiology of metabolic syndrome
- insulin resistance
| - central obesity
44
what are some features of hypothyroidism?
- weight gain
- myxoedematous facies
- menorrhagia
- hair loss
- constipation
45
which hormone is responsible for the short term regulation of serum calcium?
```
parathyroid hormone (PTH) and the active form of Fit D (calcitrol) both raise serum calcium concentrations
short term regulation of serum calcium is under the control of PTH, whereas calcitriol is responsible for longer term regulation
```
46
what is the glucagon receptor type?
GPCR
47
what are Kupffer cells?
- type of macrophage
- part of the reticuloendothelial system
- found in the liver
48
which disease is caused by an aldosterone secreting adrenal adenoma?
Conn's disease
49
what is the effect of increased parathyroid hormone secretion on plasma phosphate level?
decreased plasma phosphate
50
what does parathyroid hormone secretion do?
- stimulates osteoclast activity in bone resulting in the release of both calcium and phosphate.
- also stimulates the kidney to increase the reabsorption of calcium and decrease the reabsorption of phosphate
- more phosphates lost in the urine than gained from bone mineralisation- the net effect is to increase plasma calcium and decrease plasma phosphate
- also has indirect effects on the GI tract by promoting the formation of calcitriol (active form of Vit D)
51
which enzyme protects cells from oxidative damage by converting H2O2 to water and oxygen?
catalase
52
in which organ does cleavage of angiotensin I into angiotensin II mainly occur?
mainly converted using ACE within the lung capillaries
53
name the glycated form of haemoglobin that is measured as an indicator of average plasma glucose conc over a prolonged period of time
HbA1c
54
why might a patient with a pituitary adenoma develop visual field loss?
growth of the adenoma can cause physical compression of the optic chiasm
55
After receiving an injection of insulin, what would you expect to happen to the plasma C- peptide conc in a type 1 diabetic?
C- peptide conc would remain the same
56
what type of receptor does thyroid hormone bind to?
nuclear receptor
- hormone activated transcription factors to modulate gene expression
- thyroid hormone receptors can bind DNA in the absence of hormone, usually leading to transcriptional repression
- hormone binding is associated with a conformation change in the receptor that causes it to function as a transcriptional activator rather than a repressor
57
what happens to the serum TSH level in hyperthyroidism?
decreases below the normal range
| - due to negative feedback on the hypothalamus and anterior pituitary from thyroid gland
58
what type of hormone is cortisol?
steroid hormone synthesised from cholesterol
59
Squamous tumours of the lung, head and neck can sometimes produce a hormone that can cause hypercalcaemia. what is this hormone
Parathyroid hormone- related peptide (PTHrp)
| - acts at parathyroid hormone receptors
60
what is allosteric regulation?
the regulation of a protein by the binding of an effector molecule at a site other than the protein's active site
61
which hormone released by the hypothalamus inhibits the release of grow hormone from the anterior pituitary gland?
Somatostatin
| - also known as Growth hormone inhibiting hormone (GHIH)
62
which NT is released from primary neurones in the arcute nucleus of the hypothalamus to suppress appetite?
alphaMSH and beta-endorphin
| effect on secondary neurones results in inhibition of hunger (promotion of satiety)
63
which cell type facilitates the recycling of iron from old RBCs?
macrophages
64
what effect would an increased conc of ADH have on the reabsorption of water from urine into blood in the collecting ducts of the kidney?
promotes reabsorption of water
| results in a smaller volume of more concentrated urine
65
how would you expect the aldosterone: renin ratio to be like in a patient with secondary hyperaldoesteronism caused by renal artery stenosis?
low
secondary: low ratio
primary: high ratio
66
what is Band 3.1?
component of the red cell membrane cytoskeletal network
67
during periods of starvation, which organs contribute to gluconeogenesis?
liver and kidney
68
Where is the hormone oxytocin synthesised?
hypothalamus
69
which drug is administered for a paracetamol overdose?
acetylcysteine
70
in which nucleus of the hypothalamus are the neurones that synthesise ADH located?
paraventricular nucleus
71
which type of cell in the islets of Langerhans produce insulin?
beta cells
72
which type of cell in the islets of Langerhans produce glucagon?
alpha cells
73
what would be two signs that would be indicative of Graves' disease over other types of hyperthyroidism?
exopthalmos and Pre- tibial myxoedema
74
name a hormone produced by the placenta that exerts an anti-insulin effect on maternal metabolism
Corticotropin releasing hormone
- stimulates the release of corticotropin
human placental lactose and progesterone - do not know mechanisms
75
what effect would insulin have on the enzyme glycogen synthase in the liver?
increase in activity
| - glycogen synthase is the rate limiting enzyme in glycogen synthesis
76
the parafollicular cells within the thyroid gland secrete which substance?
calcitonin
77
what is an effect of thyroid hormone?
increase in the size of mitochondria
| - thyroid hormone stimulates an increase in both the number and size of mitochondria in cells
78
what is the mode of action of hydroxycarbamide in treating polycythaemia vera?
inhibits DNA synthesis
79
what is a polymer of glucose?
cellulose, starch and glycogen
80
is NADH considered a high or low energy signal in the cell?
high
| when levels of NADH are high in the ETC can produce ATP in abundance
81
which glucose transporter is regulated by insulin?
GLUT4
expressed by skeletal muscle and adipose tissue
responsible for insulin- regulated glucose uptake
82
thyroid hormone secreted from the thyroid gland is mostly in which form?
T4
| most is converted to T3 in the liver and kidneys
83
in which nucleus of the hypothalamus are the neurones that constitute the biological clock located?
Suprachiasmatic nucleus
84
in which nucleus of the hypothalamus are the neurones that regulate appetite located?
Arcuate nucleus
85
which endocrine gland secretes the hormone melatonin?
the pineal gland
| - melatonin is a hormone involved in setting the biological clock
86
what would be the expected total volume of blood in a 70kg man?
around 5L of blood
87
do the units mOsmol/L refer to the osmolality or osmolarity of the solution?
osmolarity
| - refers to number of osmoles per L of solution
88
A solution of normal saline has a conc of 308 mOsmol/L (9.0g per L). what conc of Na+ ions would be in this solution?
154 mM (mmol/L)
89
what term is used to describe low blood sodium?
hyponatraemia
90
what effect would an increased conc of ADH have on the reabsorption of water?
promote reabsorption of water
| smaller volume of more conc urine produced
91
in which region of the brain are the osmoreceptors located?
hypothalamus
92
define hormone
chemical signals produced in endocrine glands or tissue that travel in the bloodstream to cause an effect on other tissues
93
define paracrine
mode of signalling in which a hormone acts over a short distance via interstitial fluid to affect a response in an adjacent/ nearby cell
94
which class of hormone does cortisol fall under?
steroid hormone
| as it is derived from cholesterol
95
which class of hormone does adrenaline fall under?
amine hormone
| synthesised from the AA tyrosine
96
which class of hormone does thyroid hormone fall under
amine hormone
97
are thyroid hormones water or lipid soluble?
lipid soluble
98
what is the precursor molecule used to synthesise steroid hormones?
cholesterol
99
where is ADH synthesised?
hypothalamus
100
which hormone is released from the stomach when it is empty in order to stimulate appetite?
Ghrelin
101
which hormone is released from adipocytes and suppresses appetite?
leptin
102
which Its are released from primary neurones in the arcuate nucleus of the hypothalamus to stimulate appetite?
Neuropeptide Y (NPY) and agouti-related peptide (AgRP)
103
name the peptide precursor of the NTs alpha- MSH, beta-endorphin and ACTH (adrenocorticotropic hormone?
POMC
104
what is the name given to the regions of the pancreas that contain endocrine cells ?
islets of Langerhans
105
which type of cell in the islets of Langerhans produce insulin?
beta cells
106
what is the term used to describe the excretion of glucose in urine?
Glucosuria
| above the renal threshold for glucose (around 10 mmol/L)
107
what is the half-life of insulin in plasma?
5 minutes
108
how many disulphide bonds are present in insulin?
3
109
what is the C-peptide of insulin?
connects the A and B chains of proinsulin
| used as a clinical marker for endogenous insulin release (longer half life and so is more stable than insulin in plasma)
110
which glucose transporter is the primary transporter of glucose in pancreatic beta cells?
GLUT2
also the major transporter in liver
bidirectional transporter, allowing glucose to flow in both directions
GLUT2 allows hepatocytes to export glucose made by gluconeogenesis into the blood
GLUT2 is not regulated by insulin
111
with respect to the release of insulin, what effect would an increase in the intracellular conc of ATP have on a pancreatic beta cell?
insulin secretion would increase
- how beta cells sense an increase in plasma glucose
- more ATP produced from the metabolism of glucose results in inhibition of the ATP- sensitive K channels
- less (+) charged K leaving the cell through KATP channels results in depolarisation of the plasma membrane
- depolarisation is sensed by voltage activated calcium channels which open allowing calcium to flow down its electrochemical gradient into the cell
- this influx of calcium ions into the beta cell that activates the insulin containing vesicles causing them to fuse with the plasma membrane and release insulin
112
what type of hormone is insulin?
peptide hormone
113
is insulin a water or lipid soluble hormone?
water soluble
114
which class of receptor is the insulin receptor?
tyrosine kinase superfamily of receptors
115
which type of cell in the islets of Langerhans produce the hormone glucagon?
alpha cells
116
what is the term used to describe excessive thirst?
polydipsia
117
which type of diabetes shows markers for autoimmunity?
Type I
- Islet cell autoantibodies (ICAs) and insulin autoantibodies (IAA)
- can be detected several months/ years before onset of the disease
118
what is the classic triad of symptoms for Type I DM
- polyuria
- polydipsia
- weight loss (protein and fat metabolised due to absence of insulin)
119
what would happen to the pH of blood if excessive amount of ketone bodies were synthesised and released by the liver of a patient with type I diabetes?
pH would fall
- large amounts of ketone bodies produced
- H+ association with ketone produce a metabolic acidosis
120
what Is the normal range for plasma glucose?
3.3- 6.0 mmol/L
121
why is insulin injected and not taken orally?
peptide hormone
| broken down in GI tract to its constituent AA
122
What is the mode of action of Metformin? (for Type 2 diabetics)
inhibit hepatic gluconeogenesis
| - acts to lower plasma glucose
123
name the glycated form of haemoglobin that is measured as an indicator of average plasma glucose conc over a prolonged period of time
HbA1c
124
is the glycation of haemoglobin to form HbA1c catalysed by an enzyme?
no
| - non-enzymatic random process that disrupts protein structure and function
125
in which nucleus of the hypothalamus are the neurones that synthesise oxytocin located?
paraventricular nucleus and supraoptic nuclei
126
in which nucleus of the hypothalamus are the neurone that synthesise ADH (vasopressin) located?
supraoptic and paraventricular nuclei
127
list 6 hormones produced by the anterior pituitary gland
```
TSH thyroid stimulating hormone
ACTH Adrenocorticotropic hormone
LH luteinising hormone
FSH follicle stimulating hormone
PRL prolactin
GH Growth hormone
```
128
describe the embryological origin of the anterior lobe of the pituitary gland
up-growth of ectodermal cells from the roof of the primitive pharynx
129
list the hormones released from the posterior pituitary gland
oxytocin
| ADH
130
which organ releases IGF-1 into blood in response to growth hormone stimulation?
liver
131
which hormone released by the hypothalamus inhibits the release of growth hormone from the anterior pituitary gland?
GHIH (growth hormone inhibiting hormone)- also known as somatostatin
132
when does acromegaly occur
excess growth hormone secretion occurring after puberty after the epiphyseal plates have closed
133
what kind of receptor is the Growth hormone receptor?
tyrosine kinase receptor
134
why might a patient with a pituitary adenoma develop visual field loss?
growth of adenoma can cause physical compression of the optic chiasm
135
what is a symptom of hyperprolactinaemia in women
galactorrhoea= milky secretions from the breast
| refers to the milk secretion not due to breast feeding
136
what would be a biochemical finding in a patient with acromegaly
plasma IGF-1 above the normal range
| excessive growth hormone would stimulate IGF production by the liver and muscle - therefore an increased IGF-1 in plasma
137
what is neurogenic diabetes insipidus?
lack of vasopressin (ADH) production in the brain. Vasopressin acts to increase the volume of blood (intravascularly), and decrease the volume of urine produced.
138
define pituitary apoplexy
sudden vascular event (bleeding into or impaired blood supply) in a pituitary tumour
patients may show sudden set headache, double vision, cranial nerve palsy, visual field loss and hypopituitarism
139
what is a typical clinical consequence of untreated central (neurogenic) diabetes insipidus
hypernatraemic dehydration
| patient does not drink adequately
140
what Is the normal pattern of plasma cortisol conc
peak in the morning
| gradually declines throughout the day to the lowest levels around midnight before increasing again during the night
141
what is the role of leutinizing hormone in men?
control production of testosterone by the testis
142
what is transsphenoidal surgery
removal of pituitary tumour by inserting an endoscope and /or surgical instruments through the nose
143
which type of drug can be used to treat prolactinoma
dopamine receptor agonist
dopamine inhibits prolactin release
therefore stimulation of dopamine receptors would inhibit the release of prolactin
144
what structure joins the two lobes of the thyroid gland?
isthmus
145
the parafollicular cells within the thyroid gland secrete which substance?
calcitonin
| - located in the spaces between thyroid follicles
146
how many iodine molecules does thyroxine have?
4
147
what does the membrane bound enzyme thyroid peroxidase regulate?
- oxidation of iodide to iodine
- addition of iodine to tyrosine acceptor residues on thyroglobulin
- coupling of monoiodotyrosine and diiodotyrosine molecules within thyroglobulin
148
thyroid hormone secreted from the thyroid gland is mostly in which form?
T4
| - converted to T3 in the liver and kidneys
149
where is thyroid stimulating hormone released from?
anterior pituitary gland
150
what type of receptor does thyroid hormone bind to?
nuclear receptor
- hormone activated transcription factors to modulate gene expression
- in the absence of hormone, thyroid hormone receptors can bind DNA, usually leading to transcriptional repression
151
which thyroid hormone has the longest half life?
T4
152
what protein serves to transport thyroid hormone in plasma?
thyroxine- binding globulin (TBG)
153
which condition can be treated by the drug carbimazole?
hyperthyroidism
- pro drug which is converted to its active form methiazole in the body
- prevents thyroid peroxidase from coupling and iodinating tyrosine residues on thyroglobulin
- therefore reduces the production of thyroid hormones T3 and T4
154
Define cretinism
hypothyroidism in a neonate
| results in dwarfed stature, severe mental retardation, poor bone development, muscle weakness and GI disturbances
155
what type of hormone is thyroid stimulating hormone
glycoprotein
| - consisting of two subunits- alpha and beta
156
what would be seen with dietary iodine deficiency
low T3, T4
high TSH from anterior pituitary gland
dietary iodine deficiency always results in goitre
157
Describe Graves' diease
autoimmune disease resulting from the production of thyroid stimulating immunoglobulins (TSI)
stimulate T3, T4 release, TSH secretion decreases due tp (-) feedback
TSI outside normal (-) feedback pathway
usually present with goitre
158
which drug is commonly associated with the side effects that disrupt thyroid function
amiodarone
| - structurally smiler to thyroxine and so can disrupt thyroid function
159
why does the thyroid gland move up on swallowing
invested by the pre-tracheal fascia
160
how to describe a thyroglossal cyst
in midline and moves up on tongue protrusion
161
what type of hormone is parathyroid hormone?
peptide hormone
162
what are the actions of parathyroid hormone on the GI tract?
indirect action via promoting the formation of calcitriol (active form of Vit D)
163
what is the cell type responsible for the breakdown of bone matrix to release calcium and phosphate into the blood?
osteoclasts
164
where is calcitonin produced?
in the parafollicular cells of the thyroid gland
165
what type of hormone is calcitonin?
peptide hormone
166
What converts 7-dehydrocholesterol into Vit D3?
sunlight
167
What is the action of calcitonin on the GI tract?
has no effect
| calcitrol acts to increase the absorption of both calcium and phosphate in the GI tract
168
what are the principle cells of the parathyroid gland also called?
chief cells
| these secrete parathyroid hormone
169
how does the parathyroid gland sense plasma calcium conc?
by GPCRs that are activated by Calcium
170
what is the effect of increased parathyroid hormone secretion on plasma phosphate level?
decreased plasma phosphate
- parathyroid hormone stimulates osteoclast activity in bone resulting in the release of both calcium and phosphate
- parathyroid hormone also stimulates the kidney to increase the reabsorption of calcium and decrease the reabsorption of phosphate
- more phosphate is lost in urine than gained from bone mineralisation
171
what is the active form of Vit D?
calcitriol (1,25- dihydrocholecalciferol)
172
which tissue secretes calcitonin?
thyroid gland- parafollicular/ C cells
173
squamous tumours of the lung, head and neck can sometimes produce a hormone that can cause hypercalcaemia. what is this hormone
PTHrP= parathyroid hormone- related peptide
| this acts at parathyroid hormone receptors
174
what is the serum calcium concentration?
2.2-2.6 mM
175
what symptoms does hypocalcaemia present with?
<2.1 mmol/L
hyperexcitability in the nervous system (at NMJ)
Calcium raises the threshold for nerve membrane depolarisation and therefore makes it easier for the development of APs
- paraesthesia
- tetany
- paralysis
- convulsions
176
what symptoms does hypercalcaemia present with?
>3.0 mmol/L
- kidney stones formation (renal calculi)
- constipation
- dehydration
- kidney damage
- tiredness
- depression
177
where do the hydroxylations of Vit D take place?
1- liver
| 2- kidney
178
what is the difference between osteomalacia and osteoporosis
osteomalacia- normal structure but undermineralised (rickets in children- deformity of long bones)
osteoporosis- structurally degraded but fully mineralised
- decreased bone density but no increase in serum calcium levels
179
what is the Cori cycle
term used to describe the cycle by which the lactate produced in skeletal muscle is converted back to glucose in the liver
180
describe catabolism
oxidative and exergonic
181
what effect does the hormone insulin have on the enzyme phosphofructokinase in liver?
increases in activity
| PFK- rate limiting enzyme in glycolysis
182
what substance is used to supply the ETC with high energy electrons derived from metabolic substrates
NADH
183
transport of FAs into mitochondria requires which substance?
carnitine
| shuttle for FA across the inner mitochondrial space
184
accumulation of which substance would cause a patient's breath to smell like pear-drops?
acetone
- non enzymatic decarboxylation of acetoacetate (ketone body) forms acetone which smells like pear- drops
- pear drop smell indicates ketone body formation with a subsequent risk of ketoacidosis
185
what class of metabolite can partially replace the use of glucose as a metabolic fuel in the brain during starvation?
ketone bodies (acetoacetate and beta- hydroxybutyrate) can be used
186
name a ketogenic AA
leucine / lysine
- ketogenic as they result in the formation of acetyl- CoA
- acetyl- CoA can be used to make ketone bodies in the liver or enter the TCA cycle
- cannot synthesise glucose from these AA (not glycogenic)
187
what are examples of ketone bodies?
acetoacetate, beta-hydroybutyrate, acetone
188
what is promoted by insulin?
glucose uptake
| in adipose and muscle by causing translocation of the GLUT4 glucose transporter to the plasma membrane
189
which two organs can contribute to gluconeogenesis during a period of starvation
liver and kidney
190
for approx how long can creatine phosphate be used to replenish ATP usage in skeletal muscle during max physical exertion?
5 secs
| further ATP must be supplied by glycolysis and oxidative phosphorylation
191
an increase in ADP conc in exercising skeletal muscle would promote glycolysis by increasing the activity of which enzyme?
phosphofructokinase
| - key regulator of glycolysis stimulated by high AMP and inhibited by low ATP
192
what determines whether glycolysis will result in pyruvate or lactate production in exercising skeletal muscle?
the supply of oxygen to muscle
193
what metabolic change occurs in the liver in response to exercise?
- rate of hepatic gluconeognesis would increase
- in order to supply additional glucose for use by exercising muscle and brain
- driven by an increase in glucagon (hormone)
194
does glucagon increase or decrease during a marathon run?
increases
| - stimulates glucneogenesis by activating PEPCK and fructose-1,6-bisphosphatase
195
what symptom would be consistent with excess secretion of cortisol (hormone)
high plasma glucose
| - stimulate gluconeogenesis in liver and inhibit glucose uptake in muscle
196
the plasma conch of what hormone would increase asa a consequence of Addison's disease?
```
Adrenocorticotropic hormone ( ACTH)
- lack of (-) feedback from cortisol
```
197
why does hyperpigmentation sometimes occur in patients with Addison's disease?
decreased cortisol leads to increased expression of POMC
- removal of (-) feedback from cortisol on hypothalamus leads to increased ACTH production
- melanocyte- stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) share the same precursor molecule- POMC
- increased POMC leads to increase in both ACTH and MSH
- increased MSH results in hyperpigmentation
198
a patient has Cushing's syndrome caused by excess cortisol production from an adrenal tumour. what effect would this condition have on plasma ACTH level?
ACTH would decrease
| - excess cortisol would inhibit ACTH secretion by (-) feedback
199
which time of day would be best to take a blood sample for cortisol measurement if Cushing's syndrome is suspected?
midnight
| - should normally be low at midnight
200
which exogenous steroid is typically administered to patients as part of a suppression test to diagnose Cushing's syndrome ?
dexamethasone suppression test (DST) used to assess adrenal gland function
- normal result: decrease in cortisol
- Cushing's = cortisol not suppressed by a low dose
201
what is the synthetic analogue of ACTH used in an ACTH stimulation test
synACTHen
- synthetic ACTH analogue used to test adrenal function
- IV: normally increase plasma cortisol by >200nml/L- which can exclude Addison's disease
202
what is a potential iatrogenic cause of Addison's disease ?
adrenalectomy
| - iatrogenic effect= illness caused by medical examination/ treatment
203
which tissue contains the greatest mass of glycogen?
skeletal muscle - 300g
| around 100g in liver which is the other store
204
what effect would glucagon have on the enzyme glycogen synthase in the liver?
decrease in activity
| - glycogen synthase is the rate limiting enzyme in glycogen synthesis
205
which effect would the hormone insulin have on the enzyme glycogen phosphorylase in muscle?
decrease in activity
| - glycogen phosphorylase is the rate limiting enzyme in glycogen degradation
206
which enzyme is a major control site in the pathway of gluconeogenesis?
Fructose 1,6- bisphosphatase
| and PEPCK
207
where does FA synthesis and oxidation occur? (different answers)
```
synthesis= cytoplasm
oxidation= mitochondria
```
208
what effect would the hormone insulin have on the enzyme hormone sensitive lipase?
decrease in activity
| hormone sensitive lipase breaks down triaglyglycerol into FA and glycerol
209
which class of lipoprotein particle typically contains the greatest amount of cholesterol and cholesterol ester?
LDL
main function is the transport of cholesterol synthesised in the liver to tissues
therefore they have the highest cholesterol content
210
which class of lipoprotein particle transports dietary triacylglycerol from the intestine to tissues such as muscle and adipose tissue?
chylomicrons
| intestine -> peripheral tissues
211
which enzyme located on the capillary walls of muscle and adipose tissue facilitates the release of FAs from chylomicrons?
lipoprotein lipase
212
what does hormone sensitive lipase do?
intracellular lipase that hydrolyses stored triaclyglyerols in adipose tissue to free FA.
although HSL hydrolyses triaclyglyerols, this enzyme is involved in the mobilisation of fat stores from adipose rather than loading of FAs from chylomicrons
213
by what mechanism are LDL lipoprotein particles taken up by peripheral tissues?
receptor mediated endocytosis
214
which lipoprotein particle facilities reverse cholesterol transport?
HDL
- removes cholesterol from cholesterol- laden cells and return it to the liver
- ABCA1 protein within the cell facilitates the transfer of cholesterol to HDL
- cholesterol is then converted to cholesterol ester by LCAT
215
which enzyme is inhibited by statin drugs?
HMG- CoA reductase
216
what is the ideal plasma conc of total cholesterol?
less than 5mM (5mmol/L)
217
which metabolite can be measured in urine to provide an estimate of muscle mass?
creatinine
- breakdown product of creatine phosphate and creatine in muscle
- usually produced at a constant rate and filtered by kidneys into urine
218
which effect would insulin have on the process of protein degradation (proteolysis)?
decrease in activity
| - after a meal- there will be sufficient AA derived from ingested protein so no need to degrade body protein
219
from which AA does the body synthesise adrenaline?
tyrosine
- tyrosine and phenylalanine are precursor AA for the synthesis of catecholamines such as adrenaline, NA and dopamine.
- Thyroid hormones (T3 % T4) are also derivatives of tyrosine
220
which keto acid is used by aminotransferase enzymes to funnel the amino group of other AAs to glutamate?
alpha- ketogluterate
221
which aminotransferase enzyme is routinely measured as part of liver function test?
alanine aminotransferase and aspartate aminotransferase (ALT and AST)
- not normally found in plasma and therefore presence in blood test gives an indication of liver damage
222
down regulation of the enzymes of the urea cycle resulting from insufficient protein intake can result in which disease state?
refeeding syndrome
- low protein intake has resulted in down regulation of the urea cycle resulting in ammonia toxicity of food is re-introduced too quickly
223
which AA is utilised for the transport of ammonia from peripheral tissues to the liver?
alanine
224
during the conversion of ethanol to acetaldehyde by alcohol dehydrogenase - what is also produced?
NADH
225
does aldehyde dehydrogenase have a high or low Km for acetaldehyde?
low Km
| - acetaldehyde toxicity normally kept to a min by aldehyde dehydrogenase
226
what term is used to describe scarring of the liver cause by continuous long term liver damage?
cirrhosis
227
what is a metabolic response to chronic alcohol consumption?
increased synthesis of FAs and ketone bodies
| - increased acetyl- CoA from alcohol oxidation would lead to an increase in the synthesis of FAs and ketone bodies
228
dihulfarim can be used to support the treatment of alcohol dependence. which enzyme is inhibited by this drug?
aldehyde dehydrogenase
229
which reactive oxygen species is produced when molecular oxygen gains an electron?
superoxide
| - superoxide also an important source of other reactive oxygen species such as hydrogen peroxide and hydroxyl radicals
230
a disulphide bond in a protein can form between two resides of which AA?
thiol groups of cysteine residues
| - the other sulphur containing AA, methionine, cannot form disulphide bonds
231
which enzyme is involved in protecting cells from oxidative damage by converting superoxide to H2O2 and oxygen?
superoxide dismutase (SOD)
232
which enzyme protects cells from oxidative damage by converting H2O2 to water and oxygen?
catalase
233
which fat soluble vitamin plays an important role in protecting cells against oxidative damage by acting as a free radical scavenger?
vit E
- protects cells against lipid per oxidation
- vit c water soluble antioxidant that plays an important role in regenerating the reduced form of vit E
234
in acetaminophen (paracetamol) overdose, which toxic metabolite accumulates in the liver causing damage?
NAPQI
235
why is raised serum LDL associated with atherosclerosis?
- LDL not effectively cleared by the liver as does not have apoE
- half life for LDL in blood longer than VLDL or IDL and so is more susceptible to oxidative damage
- oxidised LDL taken up by macrophages that transform into foam cells
- foam cells accumulate in intimate of blood vessel walls to form a fatty streak
- fatty streaks can evolve into atherosclerotic plaque
- grows & encroaches on lumen of artery that can cause angina or rupture which triggers acts thrombosis by activating platelets and the clotting cascade
236
what is the treatment for hyperlipoproteinaemia?
statins eg Atorvastatin
- reduce cholesterol synthesis by inhibiting HMG-CoA reductase
bile salt seqnestrants eg Colestipol
- bind bile salts in GI tract forces liver to produce more bile acids using up more cholesterol
237
what is the difference between VLDL and HDL?
VLDL- made in liver to transport TAG to other tissues
| HDL- made in liver and intestine to transport cholesterol from cholesterol- laden cells and return to liver
238
what are the clinical signs of hyperlipoproteinaemia?
- xanthelasma- yellow patches around eyes
- tendon xanthoma- nodules on tendon
- corneal arcus- white circle around eye
239
when do chylomicrons appear in the blood?
present in blood normally 4-6hrs after a meal
| have a 'creamy appearance'
240
what are the three key enzymes in gluconeogenesis?
PEPCK: converting oxaloacetate
fructose-1,6-bisphosphatase: converting fructose-1,6-bisphosphate
glucose-6-phosphatase: converting glucose-6-phosphate
241
what are two enzymes that regulate glycogen metabolism
glycogen synthase- synthesis
glycogen phosphorylase- degradation
- irreversible reactions
242
what are the key enzymes for glycogenolysis
- glycogen phosphorylase alpha 1-4 or debranching enzyme alpha1-6
- phosphoglucomutase
243
what are the key enzymes for glycogenesis
- hexokinase
- phophoglucomutase
- G1P uridylyltransferase
- glycogen synthase alpha1-4 or branching enzyme alpha1-6
244
what is phenylketonuria (PKU)?
autosomal recessive disorder
deficiency in phenylalanine hydroxylase
- enzyme usually converts phenylalanine into tyrosine- precursor for NA, adrenaline, dopamine, melanin, thyroid hormone and protein synthesis.
- accumulation of phenylalanine in tissue, plasma and urine
- phenylketones in urine= musty smell
245
what is the treatment for phenylketonuria?
- low phenylalanine diet enriched with tyrosine
| - avoid high protein foods
246
what is homocystinurias?
autosomal recessive
problem breaking down methionine
excess homocysteine in urine - elevated homocysteine associated with cardiovascular disease
affects CT, muscles, CNS and CVS
247
what is the treatment for homocystinurias?
- low methionine diet
- avoid meat, fish, cheese and eggs
- cysteine, vit B6, betaine, B12 and folate supplements
248
how is ammonia toxic?
- readily diffusible and toxic to the brain
- interference with AA transport and protein synthesis
- alkaline pH effects
- alteration of the blood brain barrier
249
which keto acid is used by aspartate aminotransferase enzymes to funnel the amino group of other AAs to aspartate?
oxaloacetate
250
name some vitamins that act as free radical scavengers
vit E
- lipid soluble antioxidant that protects against lipid peroxidation
vit C
- water soluble antioxidant that regenerates reduced form of vit E
251
what is a respiratory burst?
rapid release of superoxide and hydrogen peroxide from phagocytic cells (neutrophils and monocytes)
ROS and peroxynitrite destroy invading bacteria - antimicrobial defence system
