Autonomic Control of Metabolism Flashcards
What is the process of synthesising noradrenaline from tyrosine?
In the terminal button of a neuron tyrosine is converted into DOPA by tyrosine hydroxylase. DOPA is then converted into Dopamine by DOPA decarboxylase. The Dopamine travels through a vesicular monoamine transported into a vesicle where it is then converted into noradrenaline by Dopamine beta-hydroxylase
How does an action potential cause the release of neurotransmitters?
When the action potential reaches the axon terminal it causes calcium ion channels to open increasing the Ca+ concentration in the cell. This causes the vesicle to fuse with the cell membrane, causing the neurotransmitters to be released into the synapes
How is the action of noradrenaline terminated?
Reuptake into presynaptic neuron
Enzymatic breakdown
Where is adrenaline made?
Adrenal medulla
Which enzyme converts noradrenaline into adrenaline?
PNMT
True or False:
Alpha-receptors are only activated by noradrenaline
False
Both adrenaline and noradrenaline activates the alpha-receptor but noradrenaline activates it more
Which molecule activates a beta-receptor more, adrenaline or noradrenaline?
Adrenaline
Which cytoplasmic loop of the GPCR is the most important to function?
3rd
It couples to G-proteins
In which tissues are Beta1-receptors found?
Heart
Liver
Skeletal muscle
In which tissues are Beta2-receptors found?
Lungs
Blood vessel beds of skeletal muscle
In which tissues are Beta3-receptors found?
Adipose cells
What is the effect of beta-receptor activation in the liver?
Glycogenolysis (B1)
What is the effect of beta-receptor activation in the skeletal muscle?
Glycogenolysis (B1)
Glucose uptake (B2)
Thermogenesis (B3)
What is the effect of beta-receptor activation in white adipose tissue?
Lipolysis (B3)
What is the effect of beta-receptor activation in brown adipose tissue?
Thermogenesis (B3)
In the liver, which enzymes are activated/inhibited by adrenaline?
Activated: glycogen phosphorylase
Inhibited: glycogen synthase
In the muscle, which enzymes are activated/inhibited by adrenaline?
Activated: glycogen phosphorylase
Inhibited: glycogen synthase
In the fat, which enzymes are activated/inhibited by adrenaline?
Activated: lipase
True or False:
Adrenaline can stimulate glucose uptake into muscle independent of insulin
True
What is the adrenal cortex?
the outer portion of the adrenal gland located on top of each kidney. The adrenal cortex produces steroid hormones which regulate carbohydrate and fat metabolism and mineralocorticoid hormones which regulate salt and water balance in the body
What is the adrenal medulla?
the inner portion of adrenal gland. The adrenal medulla makes adrenaline and noradrenaline.
What is adrenaline?
a hormone that is secreted by the adrenal medulla in response to stress and increases heart rate, breathing rate and blood pressure, and raises the blood levels of glucose and lipids
What is an alpha-adrenoreceptor?
a class of GPCRs targeted by noradrenaline and adrenaline. Common effects of α-receptors include vasoconstriction of veins and a decrease in motility of smooth muscle in the GI tract
What is the autonomic nervous system?
the part of thenervous systemthat controls and regulates the internal organs without any conscious recognition or effort by the organism. Theautonomic nervous systemcomprises two antagonistic sets ofnerves, the sympathetic and parasympatheticnervous systems.
What is a barbituate?
a drug that acts as a central nervous system depressant, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia
What is a Beta1-receptor?
a class of GPCRs targeted by noradrenaline and adrenaline. Common effects of the β1-receptor include an increase in cardiac output, glycogenolysis, renin secretion from the kidneys and ghrelin secretion from the stomach.
What is a Beta2-receptor?
a class of GPCRs targeted by noradrenaline and adrenaline. Common effects of the β2-receptor include smooth muscle relaxation, lipolysis, glycogenolysis and insulin secretion
What is a Beta3-receptor?
a class of GPCRs targeted by noradrenaline and adrenaline. Common effects of the β3-receptor include enhancement of lipolysis in white adipose tissue and thermogenesis in brown adipose tissue
What is brown adipose tissue (BAT)?
a type of adipose tissue with its primary function being thermoregulation. Brown adipocytes contain numerous small droplets of lipids and a mu higher number of mitochondria, which give it its brown appearance
What is clenbuterol?
a drug that acts as a β2 agonist which increases oxygen uptake and glycogenolysis. Clenbuterol is a common performance enhancing drug
What is cytochrome p450?
proteins of the superfamily containing heme as a cofactor. They are, in general, the terminal oxidase enzymes in electron transfer chains
What is diazepam?
a drug, also known as Valium, that is a part of the benzodiazepine family that produces a calming effect
What is dobutamine?
a drug that acts as a β1 agonist which increases cardiac output. This drug is commonly used to treat heart failure
What is DOPA decarboxylase?
an enzyme that catalyses several reactions with the most important being the conversion of L-DOPA to dopamine which is a step in the synthesis of noradrenaline
What is dopamine?
a type of neurotransmitter that acts in the brain that is also required to synthesis noradrenaline in the adrenal medulla
What is dopamine β-hydroxylase?
an enzyme that catalyses the conversion of dopamine into noradrenaline in the adrenal medulla
What does innervated mean?
to control an organs activity through nerves
What is isoprenaline?
a drug that acts as a non-selective agonist of β-receptors. This drug is commonly used to treat bradycardia (slow heart beat) and heart block
What is monoamine oxidase (MAO)?
an enzyme required to breakdown, and hence deactivate, noradrenaline (and adrenaline) after its reuptake into the neuron
What is metoprolol?
a drug that acts as a β1 antagonist which is used to treat high blood pressure, poor blood flow to the heart and abnormally high heart rate
What is noradrenaline?
a substance that acts as both a neurotransmitter and hormone, secreted in the central nervous system, at the nerve endings of the sympathetic nervous system, and by the adrenal medulla
What is the pharmacodynamics phase?
the mechanism of action of the drug on the body tissues; that is , the response of tissues to specific chemical agents at various sites in the body
What is the pharmacokinetics phase?
the phase that looks at the concentration of a drug during the process of absorption, distribution, metabolism and excretion
What is PNMT?
an enzyme found primarily in the adrenal medulla that catalyses the conversion of noradrenaline into adrenaline
What are pro drugs?
a biologically inactive compound which can be metabolised in the body to produce a drug
What is propranolol?
a drug that acts as a non-selective antagonist which is used to treat high blood pressure, irregular heartbeat and tremors
What is salbutamol?
a drug that acts as a β2 agonist which act as bronchodilators. It is used to treat asthma
What is serotonin?
a neurotransmitter derived from tryptophan than is primarily found in the GI tract, blood platelets and CNS
What does sublingual mean?
situated or applied under the tongue
What is the sympathetic nervous system?
a branch of the autonomic nervous system that is responsible for the fight or flight response that includes acceleration of heart rate, widening of bronchial passages, decreased digestion, constriction of blood vessels and many other things
What is systemic circulation?
the part of the cardiovascular system which carries oxygenated blood away from the heart to the body, and returns deoxygenated blood back to the heart
What is tyrosine hydroxylase?
an enzyme required for the synthesis of noradrenaline. It catalyses the conversion of tyrosine into DOPA
What is a vesicular monoamine transporter (VMAT)?
transporters that are responsible for the uptake of dopamine into synaptic vesicles where it can then be converted into noradrenaline
What are xenobiotics?
a chemical substance found within an organism that is not naturally produced or expected to be present within the organism
What is the effect of β1-adrenoreceptors activation in the heart?
Increased force of contraction
Increased heart rate
Increased cardiac output/stroke volume
What are the effects of β1-adrenorecptor antagonists?
Reduction in exercise tolerance: small increase in heart rate and force and small increase in blood flow in response to exercise
True or False:
The bronchial smooth muscle is largely innervated by the sympathetic nervous system
False
It is not innervated by the sympathetic nervous system
What type of β receptor regulate bronchodilation?
β2 adrenoreceptors
What would a β-adrenoceptor blocker do in the lung?
Cause the vessels to constrict
What would a β-adrenoceptor blocker do in the liver?
Prevent the release of glucose
What are the side-effects of β2 agonists?
Skeletal muscle tremor
What would a β2 agonist do in the skeletal muscle?
Dilate arterioles and increase blood supply to muscles.
Increased twitch tension of fast muscle (decrease slow muscle)
Increased instability of reflex control of muscle length (tremor)
What is an example of a β1 agonist?
Dobutamine
What is an example of a β1 antagonist?
Metoprolol
What is an example of a β2 agonist?
Salbutamol or clenbuterol
What is an example of a nonselective β adrenoreceptor agonist?
Isoprenaline
What is an example of a nonselective β adrenoreceptor antagonist?
Propranolol
What are the expected effects of β-adrenoreceptor antagonists?
Fatigue (during exercise)
Cold extremities
Narrowing of bronchi
Steadiness of voluntary muscle
What are the expected effects of β-adrenoreceptor agonists?
Increased heart rate and force
Increased blood flow to voluntary muscles
Widening of bronchi
Enhanced muscle tremor
What are the functions of the liver?
Distribution of nutrients All types of metabolism Excretion of bile acids and urea Destruction of toxic substances Depot of iron, vitamins
What are the stages of the pharmacokinetics phase?
ADME!
Absoption
Distribution
Metabolism
Excretion
What characteristics must a drug have to be effective?
Lipid solubility (to move into cells) Water solubility (dissolve in blood and excretion)
True or False:
Most hydrophilic drugs are less biotransformed and excreted unchanged
True
Where is the main site from the metabolism of drugs?
Liver
Which organ is responsible for filtering drugs?
Kidneys
What does phase 1 of metabolism involve?
The oxidation, reduction and/or hydrolysis of drugs by liver microsomal enzymes in order to make the drugs more polar
What family of enzymes are responsible for phase 1 of metabolism?
Cytochrome p450
What does phase 2 of metabolism involve?
Conjugation of the drug by liver cytosolic enzymes that add an endogenous molecule to the drug to increase its polarity (and hence water solubility)
Which enzyme is responsible for phase 2 of metabolism?
UDP glucurononyl transferase
What factors influence the activities and levels of CYP enzymes?
Nutrition Smoking Alcohol Drugs Environment Genetic Polymorphism
What factors affect drug metabolism?
Genetic variability Race and Ethnicity Age Sex Diet Drug interactions Disease
What happens in the body when a large dose of paracetamol is taken?
CYP450 metabolism is dominant which converts the paracetamol into large amounts of NAPQI which results in the destruction of liver cells and hepatotoxicity
Why does a large dose of paracetamol lead to hepatotoxicity?
Toxicity can arise when glutathione (the enzyme that detoxifies NAPQI) is depleted or normal conjugation is prevented
