Metabolism Flashcards
What are the classifications for BMI weights
What is malnutrition
a condition caused by imbalance in what an individual eats and what is required
what is malabsorption
a condition caused by the failure to absorb nutrient properly
What is undernutrition
a condition caused by an eating disorder
what is homeostasis
the maintenance of a constant internal environment within limits of a dynamic equilibrium
How do you calculate the BMI
BMI = Weight (kg) / Height ^ 2 (meters)
what is metabolism
the chemical reactions that happen in organisms to sustain life
What enzyme turns HMG acid into Cholesterol
HMG Co enzyme A reductase
In metabolism of Acetyl Co-A, what regulates the production of ketone bodies or cholesterol
Ketone Bodies are increased in response to Glucagon
Cholesterol is increased in response to Insulin
What is the intermediate between Acetyl Co-A and Ketone Bodies or Cholesterol?
Hydroxylmethyly Glutaric Acid
What is the level of ketone bodies in the blood that suggest diabetes?
More than 10mM
What are the products of Beta Oxidation of fatty acids
Acetyl Co-A, NADH, FADH2
No ATP
What are the three ketone bodies and their properties
Acetone, acetoacetate and beta-hydroxybutyrate. water soluble and can enter the tri-carboxycylic acid chain.
Which parts of the body requires glucose for energy exclusively
Cornea of the eye, medulla of the kidney, testes, RBC, CNS preferentially
Name 3 different classes of lipids and 2 examples of each
Fatty Acids - triacylglycerols, phospholipids, fatty acids
Hydroxy Methyl Glutaric acid derivatives - Ketone Bodies and Cholesterol
Vitamins - A, D, E, K
Where are ketone bodies and cholesterol synthesised
liver
Where are fatty acids metabolised
Most tissues in the body with mitochondria, except CNS as difficulty in crossing the blood brain barrier.
where is glycogen stored
liver and muscles
what are the advantages of glycogen
stable, large surface area for rapid access, osmotically neutral
What is glycogenesis
Creation of glycogen, using hydrolysis -
Glucose - glucose 1 phosphate - glucose 6 phosphate + UTP - UDP glucose + glycogen
What enzymes are used in glycogenesis
1, Hexokinase = glucose - glucose 6 phosphate
2, Phosphoglucomutase = glucose 6 phosphate - glucose 1 phosphate
3, Glycogen synthase and Branching Enzyme - UDP glucose + glycogen
What is gycogenlysis
Degradation of glycogen, phosphorylation reaction
glycogen - glucose 1 phosphate - glucose 6 phosphate - glucose
What are the enzymes in glycogenlysis
1, Debranching enzyme & amp; Glycogen phosphorylase = Glycogen - glucose 1 phospate
2, Phosphoglucomutase = glucose 1 phospate - glucose 6 phosphate
3, Glucose 6 phosphatase = glucose 6 phosphate - glucose
What effect does glucagon have on glycogen
Activates glycogenlysis - phophorlyation of glycogen synthase decreasing activity and phosphorylation of glycogen phosphorylase increasing activity
What effect does insulin have on the glycogen
Glycogenesis - dephosphorylation of glycose synthase leading to activation, dephosphorylation of glycogen phosphorylase leading to inhibition
Give two examples of glycogen storage diseases and the enzymes they effect
Von grieke disease - glucose 6 phosphatase, cannot convert glucose 6 phosphate to glucose in the liver
McArdle disease - glycogen phosphorylase cannot breakdown glycogen in liver or muslce
What are the advantages of lipid storage
bulk, energy rich, anhydrous, highly calorific - stoerd as triacyglycerol in adipose tissue.
What effect does glucagon and insulin have on fat stores
Glucagon - phosphorylates Hormone sensitive lipase activation
Insulin - dephosphorylates Hormone sensitive lipase deactivation
Name three energy storing molecules apart from ATP
Phosphoenolpyruvate
1,3 - Bisphosphoglyerate
Creatine Phosphate
Where is Creatine Phosphate, what does it do and how is it made
Creatine is transformed into creatine phosphate with the enzyme creatine kinase, this requires energy of ATP.
Creatine Phophate is a more stable form of energy than ATP but only lasts a short time and is produed in muscles when there are high concentrations of ATP
What is creatinine
Creatinine is formed spntaneously from the breakdown of creatine or creatine phosphate. High levels in urine suggest muscle wasting.
What are the characteristics of monosaccharides and give examples
Partially oxidised, hydrophilic - glucose, fructose, galactose, ribose, glyceraldehyde
What is the first step in glycolysis
glucose to glucose 6 phosphate
enzyme - hexokinase or glucokinase in liver
What is the commiting step in gycolysis
Fructose 6 phosphate - fructose 1,6, bisphosphate
Phosphofructokinase
What is the second step in glycolysis
glucose 6 phosphate - fructose 6 phosphate
Isomerase
Which two steps require ATP in glycolysis
Step 1 creation of glucose 6 phosphate
Step 3 creation of fructose 1,6 bisphosphate
What are the net products of gycolysis
2 x (pyruvate + 2ATP + NADH + H + H20)
What are the two products of step 4 in glycolysis
Dihydroxyacetone phosphate - that can become glycerol phosphate making phospholipids and TAG
Glyceraldehyde - 3 - phosphate
Enzyme is Aldolase
What is substrate level phosphorylation
direct creation of ATP from carbohyrates, rather than indirectly from ATP synthase in the electron transport chain
What are the advantages of glycolysis
Many small steps makes, Little energy lost, can be controlled by multiple enzyes, versatility to connect with other metabolic pathways
Anaerobic
Name an enzyme that breaksdown polysaccharides and disaccharides
Amylase - polysaccharides in the mouth a1,4 glycosidic bonds
Sucrase - glucose/fructose
lactase - galactose/glucose
Maltase - glucose/glucose
Absorption of Glucose
In gut - sodium dependent glucose transporter SGLT
GLUT 1- RBC
GLUT 2 - both ways - liver, basolateral surface of epithelia, kidneys
GLUT 3 - nerurons
GLUT 4 - insulin dependent muscle / adipose tissue
Name 2 alternative products of glycolysis
2,3 Bisphosphoglycerate (2,3BPG) - from 1,3, BPG in step 6. uses enzyme bisphosphoglycerate mutase
Glycerol phosphate - from dihydroxyacetone phosphate in step 4, used in producing lipids
How is glycolysis regulated
Product inhibiton - high NADH leads to inhibition of Step 6
Allosteric inhibition - Phosphofructokinase in Step 3 activated by ATP inhibitied by AMP
Dephosphorylation - Glucagon activates protein Kinase A, which phosphorylates Pyruvate Kinase in step 10 of glycolysis
What is the purpose of the lactate pathway
To generate oxidised NAD+ to be used in RBC for glycolysis
Cannot be retrieved from stage 4 of carbohydrate metabolism in electron transfer chain
When does lactate pathway happen
In RBC to generate NAD+, in muscle when insufficient oxygen
What is the process of lactate pathway
NADH + H + pyruvate — lactate + NAD+
lactate dehydrogenase is the enzyme, reversibly
Which tissues can use lactate
Cardiac muscle converts it back to pyruvate
Liver can convert it back to glucose / glycogen
What are the consequences of high lactate
Lactic acidosis >5mM
Fructose pathway involves which steps
Fructose - Fructose 1 phosphate - 2x Glyceraldehyde-3-phosphate - glycolysis
What are the consequences of difunctional enzymes in the fructose pathway
Fructokinase - no problem, fructose excreted in urine
Aldose - fructose 1 phosphate builds up in the liver causing toxic damage
What is the galactose pathway
Galactose - Galactose 1 phosphate - Glucose 1 phosphate - Glucose 6 phosphate - Glycolysis
Enzymes - galactokinase and galactose 1-P uridyl transferase
What are the consequences of enzyme deficiencies in the galactose pathway
galactokinase - increase in galactose which is forced into the galactitol pathway
glactose 1-P-uridyl transferase - galactose 1 phosphate builds up in liver causing disease and build up of galactose
What are the consequences of increased galactose
galactose converted into galactitol. Using NADPH in NADP+. By aldose reductase
NADPH is important in creating reduced glutathione, which prevents formation of inappropriate disulphide briges. So without it can cause cataracts in the eye
At what stage in glycolysis can the pentose pathway begin? what is the purpose of the pentose pathway?
Stage 1 - glucose 6 phosphate to C5 sugar?
Produces reducing power NADPH required for lipogenesis and glutathione reduction
Produces C5 sugars for nucleotides
What enzyme works on the pentose 5 pathway
glucose 6 phosphate dehydrogenase
What are the products of each rotation of the Kreb’s cycle
3 NADH, 1 FADH2, 1 GTP, oxoacetate, 2 CO2
What are the 2 irreversible steps in the Kreb’s cycle and the enzymes that regulate them
Isocitrate - ketoglutarate & amp & CO2 = isocitrate dehydrogenase
Ketoglutarate - Succinyl CoA = keoglutarate dehydrogenase
What effects the rate of reaction in the Kreb’s cycle
ADP - activates isocitrate dehydrogenase
ATP/ NADH - inhibit isocitrate dehydrogenase and ketoglutarate dehydrogenase
What are the products of the Kreb’s cycle used for
citrate = fatty acids
ketoglutatrate / malate = amino acids
FADH NADH2 = carriers of reducing power in electron transport chain
Where does glycolysis, Kreb’s cycle, and Electron Transport Chain take place
cytoplasm, matrix of mitochondria, inner membrane of mitochondria
Where does the fructose, galactose and pentose 5 sugar metabolism take place in the cell.
liver, liver, all cells but mostly liver - all take place in cytoplasm
What enzyme converts pyruvate to acetyl CoA, where is it found and what does it produce
pyruvate dehydrogenase, takes pyruvate into the mitochondria, produces CO2 and NADH + H
Pyruvate dehydrogenase is activated and inhibited by what products
Activated by - ADP, NAD+, Insulin, Pyruvate
Inibited by - ATP, NADH, Glucagon, Acetly CoA
What is the difference between substrate and oxidative phosphorylation
substrate - direct transfer of phosphate group to ADP or GDP, happens in cytoplasm, not oxygen dependent, produces less ATP
oxidative - happens on inner membrane of mitochondria, using energy from electrons to generation a proton motive force that activate ATP synthase, requires oxygen, produces more ATP
How many ATP molecules do the reducing agents create
NADH - 2.5 ATP
FADH2 - 1.5 ATP
What is the molecule that transports protons across the inner membrane of the mitochondria
proton translocating complext - 3 types
ATP synthase - inward bound
The inner membrane of the mitochondria is highly impermeable to protons.
What regulates the proton transport chain
Build up of ATP, lowers ADP, meaning less H+ can re-enter the matrix build up of H+ on intermembrane space is such that hydrogen pumping trhrough proton translocating membrane ceases
What inihibits the oxidative phosphorylation
cyanide - blocks one of the proton translocating complexes preventing the passage of electrons to oxygen.
CO - blocks provision of oxygen
What are uncouplers and give examples
They separate the proton translocating complex from the ATP synthase. By increasing the permeability of the inner mitochondial membrane.
Thermogenin, UCP 1, dinitrophenol
Common in brown adipose tissue and hibernating animals to produce heat
What are the essential amino acids
Isoleucine, leucine, threonine, histidine, lysine, methionine, phenylalanine, tryptophan, valine
What is transamination
Exchange of and amino group between an amino acid and keto acid, creating a different amino acid. Uses an aminotransferase enzyme - example alanine transaminase, aspartate transaminase
Alpha ketoglutarate - glutamate
Oxaloacetate - aspartate
What is deamination, and give example
Removal of amino group from amino acids for excretion
Glutamine - Glutamate - ketoglutarate
GIve two examples of amino acid clinical problems
Phenylketonuria: Phenylalanine - tyrosine, using phenylalnine hydroxylase. High phenylalanine causes mental retardation by inhibitin mitochondrial metabolism. Detected in urine, or heel prick of new borns.
Homocystinuria: Homocysteine - Cystathionine, by cystathionine beta synthase. High homosysteine damages connective tissue, CNS, muscle.
What are the two ways of processing ammonia and transporting it in the blood
Glutamate + ammonia = glutamine in tissues safe to transport in blood, used in liver to convert to urea or excreted in kidneys
Pyruvate + ammonia = alanine
What are the advantages of urea?
Non toxic, metabolically inert, high nitrogen content, soluble, chemically inert
What is the urea cycle inputs
glutamate and aspartate
what are the dangers of ammonia
extremely toxic to brain, readily dissolvable, alters pH, effects Kreb’s cycle, metabolism
What is refeeding syndrome
When patients are severly malnourished, they have insufficient protein and exnzymes to process amino acids into safe urine. Consequently ammonia levels increase severely. This can cause death, BMI
Give uses for 5 amino acids
Histidine - histimine Cystein - glutathione Arginine - nitric acid Glycine - hae Tyrosine - Thyroid hormones
What are apoproteins
They are proteins that provide structural support to phospholipid bilayers, and idenitify the vessicles and act as cofactors.
What are lipoproteins
Phospholipid vesicles, with apoprotein structural units containing a hydrophobic lipid core
Where are lipoprotein lipases found and what interacts with them
On capillary walls, interact with apo C on chylomicrons, VLDL, IDLs
How is artherosclerosis caused
LDLs, lack Apo E and Apo C, they are not effectively cleared by the cells in the body. The cholesterol contents can get oxidised, as they hang in the blood for so long. The LDLs are then consumed by macrophages, which turn into foam cells, causing a fatty streak in the intima of blood vessels, this can narrow the lumen, or burst and cause a MI/ stroke
What Apoproteins do HDL have and what are their purpose
ATP Binding Cassete Protein (ABCA1) needed on tissues to form and HDL with cholesteroll and it will transport the cholesterol to the liver for processing. Deliver to liver for use in producing bile, or steroidal cells producing hormones
Give two examples of hyperlipoproteinaemias
Type 1 - High chylomicrons, defective LPL
Type 2 - Defective LPL, high chance of artherosclerosis
Type 3 - High IDL and chylomicrons, defective Apo E
Give three symptoms of hypocholerstolaemia and three treatments
Xanthelasma - yellow eyelid blotches
Tendon Xanthoma - nodules on tendons
Corneal Arcus - white rings around iris
diet, exercise, cholesterol sequestration in diet, statins target HMG-CoA reductase
What disease are aused by oxidative stress
Mulitple Sclerosis, CVD, Parkinson’s,, Arthritis, Alzheimers
What is a free radical and give examples
an atom with an inpaired electron - hydroxyl radical (most damaging), superoxide, nitric oxide
What damage can free radicals cause
DNA - misspairing of nucleotides, strand breaks, damage to the backbone
Protein - change structure, gain or loss - eg. create cysteine and inappropriate disulphide bonds
Lipids - bind ot unsaturated fatty acids creating lipid radicals - eg. lipid peroxyl radical. Last a long time in the blood
Soures of biological oxidation
Endogenous - electron transport chain, nitric oxide synthase, NADPH oxidase
Exogenous - radiation, pollutants, tobacco, toxins
What is a respiratoy burst
A release of free radicals by a phagocyte to destroy pathogens - typically using NADPH oxidase, Nitric oxide, and hydrogen peroxide
Name 4 different defences against free radicals in the body
Glutathione - in reduced from can accept free radicals to form a disulphide bridge between two cystein amino acids
Catalase - Catalase - hydorogen peroxide to water and oxygen
Vitamin E - prevents lipid peroxidation with the help of vit C
Superoxide dismutase converts super oxide to hydrogen peroxide and oxygen.
Two diseases that increase free radival vulnerability
Galactosaemia - causes Galactose to be converted to Glactitol by the enzyme aldose reductase. Using NADPH and preventing any for regenerating Glutathione
Glucose 6 posphate dehydrogenase non function - cannot produce pentose sugars from gluose 6 phosphate, so not creating NADPH.
Consequences Heinz bodies and anaemia from RBC, cataracts
What are the consequences of Paracetamol
Excess paracetamol creates NAPQI - depletes gluthione and causes oxidative damage to the liver.
Antidote is acetylcysteine - regenerates the glutatione
give three examples of positive feedback in the body
ovulation, lactation, blood clotting
What is a zeitgeber
environmental stimuli - light, temperature, activity, diet
what is a suprachiasmatic nucleus
collection of neurons in the brain
What is an osmole
the amount of substance required to dissociate in water to form one mole of osmotically active particles
What is osmolality
the number of osmoles per kilogram of solution
How many litres of water in a 70kg man
42 L - 28L intracellular, 9.4L extracellular, 4.6L blood,
Give examples of 5 hormones produced by organs not glands
stomach - ghrelin, gastrin Liver - IGF1 Adipose - Leptin Kidney - Renin Calcitrol Heart - ANP / BNP
What type of hormone are insulin and glucagon
small polypepetide, soluble hormones
What are examples and characteristics of amino acid hormones
adrenaline, noradrenaline, thyroid - former water soluble latter lipid soluble.
Give examples of glycoprotein hormones and their character
Large, water soluble - Lutenizing hormone, Follicle stimulating hormone, thyroid stimulating hormone
What are the advantages of binding proteins to non-soluble hormones
Increase solubility, half life and accessability.
What are the differences between the water soluble hormones and lipid soluble hormones
Cannot cross the plasma membrane for water soluble hormones, require carrier protein. Eg. G-protein for adrenaline and Insulin for Tyrosine Kinase
What is the region of the skull that holds the pituitary gland
sella turcica
What does the hypothalmic / pituitary axis control
growth, lactation, reproduction, adrenal gland, thyroid gland, water , puberty
Where does the pituitary develop from
anterior pituitary - ectoderm
posterior pituitary - nervous system
What are tropic hormones and their examples
They effect the release of other hormones. Released from anterior pituitary gland, following neurosecretory stimulation from the hypothalamus.
thyrotropin releasing hormone - thyroid stimulating hormone
cortiotropin releasing hormone - adenocorticotropic hormone
prolacti releasing hormone - prolactin
what is diabetes
chronic hyperglycaemia
List the main differences between Type 1 and Type 2 diabetes
Type 1 - in young people, rapid onset, destruction of beta cells, treated with insulin
Type 2 - generally occurs in middle age, gradual onset, simultaneous loss of beta cells and tissue resistance to insulin, initially untreatable with insulin
What are the genetic markers for diabetes type 1 and symptoms and diagnostic
polydipsia, polyuria, weight loss - HLA DR3 and HLA DR4
what are the symptoms of ketonacidosis
hyperventilation, prostration, nausea, vomiting, dehydration
what are the symptoms of type 2 diabetes
polydipsia, polyuria, weight loss
tiredness, lethargy, persistent infections, infected feet.
what are the diagnostic blood tests for diagnosing diabetes
> 7mMol fasting
>11.1mMol/L random
Name two medicines for type 2 diabetes and their function
Metformin - decrease insulin resistance and decrease gluconeogenesis
Sulphonureas - increase insulin release from pancreas cells
what level of HBA1c suggests hyperglycaemia
> 10% glycated HBA1c
what are the consequences of hyperglycaemia
high glucose creates sorbitol via aldose reductase, using NADPH, which can no longer be used for reducing glutathione and protecting against disulphide bridges.
Macrovascular - stroke, MI, poor circulation
Microvascular -
retinopathy weak vessels burst,
glaucoma (change in osmotic pressure of the eye),
nephropathy (decrease blood vessel diameter and infection), neuropathy (change in micro blod vessels for neurons)
diabetic feet (poor blood supply)
What is the structure of insulin and how is it produced and released
alpha and beta chain, 3 disulphide brides, 110amino acids long.
preproinsulin chain in ER
proinsulin in Golgi apparatus
storage granules Insulin and c peptide
secretion - high glucose, absorbed through GLUT2, increase ATP, open ATP sensitive K+channels, depolarsing cell releasing Ca2+, releasing granules.
At what stage in glycolysis can the pentose pathway begin? what is the purpose of the pentose pathway?
Stage 1 - glucose 6 phosphate to C5 sugar?
Produces reducing power NADPH required for lipogenesis and glutathione reduction
Produces C5 sugars for nucleotides
What enzyme works on the pentose 5 pathway
glucose 6 phosphate dehydrogenase
What are the products of each rotation of the Kreb’s cycle
3 NADH, 1 FADH2, 1 GTP, oxoacetate, 2 CO2
What are the 2 irreversible steps in the Kreb’s cycle and the enzymes that regulate them
isocitrate - ketoglutarate & CO2 = isocitrate dehydrogenase
ketoglutarate - Succinyl CoA = keoglutarate dehydrogenase
What effects the rate of reaction in the Kreb’s cycle
ADP - activates isocitrate dehydrogenase
ATP/ NADH - inhibit isocitrate dehydrogenase and ketoglutarate dehydrogenase
What are the products of the Kreb’s cycle used for
citrate = fatty acids
ketoglutatrate / malate = amino acids
FADH NADH2 = carriers of reducing power
Where does glycolysis, Kreb’s cycle, and Electron Transport Chain take place
cytoplasm, matrix of mitochondria, inner membrane of mitochondria
Where does the fructose, galactose and pentose 5 sugar metabolism take place in the cell.
liver, liver, all cells but mostly liver - all take place in cytoplasm
What enzyme converts pyruvate to actyl CoA, where is it found and what does it produce
pyruvate dehydrogenase, takes pyruvate into the mitochondria, produces CO2 and NADH + H
Pyruvate dehydrogenase is activated ad inhibited y what products
Activated by - ADP, NAD+, Insulin, Pyruvate
Inibited by - ATP, NADH, Glucagon, Acetly CoA
What is the difference between substrate and oxidative phosphorylation
substrate - direct transfer of phosphate group to ADP or GDP, happens in cytoplasm, not oxygen dependent, produces less ATP
oxidative - happens on inner membrane of mitochondria, using energy from electrons to generation a proton motive force that activate ATP synthase, requires oxygen, produces more ATP
How many ATP molecules do the reducing agents create
NADH - 2.5 ATP
FADH2 - 1.5 ATP
What is the molecule that transports protons across the inner membrane of the mitochondria
proton translocating complext - 3 types
ATP synthase - inward bound
The inner membrane of the mitochondria is highly impermeable to protons.
What regulates the proton transport chain
Build up of ATP, lowers ADP, meaning less H+ can reenter the matrix build up of H+ on intermembrane space is such that hydrogen pumping trhrough proton translocating membrane ceases
What inihibits the oxidative phosphorylation
cyanide - blocks one of the proton translocating complexes preventing the passage of electrons to oxygen.
CO - blocks provision of oxygen
What are uncouplers and give examples
They separate the proton translocating complex from the ATP synthase. By increasing the permeability of the inner mitochondial membrane.
Thermogenin, UCP 1, dinitrophenol
Common in brown adipose tissue and hibernating animals to produce heat
What are the essential amino acids
Isoleucine, leucine, threonine, histidine, lysine, methionine, phenylalanine, tryptophan, valine
What is transamination
Exchange of and amino group between an amino acid and keto acid, creating a different amino acid. Uses an aminotransferase enzym - example alanine transaminase, aspartate transaminase
Alpha ketoglutarate - glutamate
Oxaloacetate - aspartate
What is deamination, and give example
Removal of amino group from amino acids for excretion
Glutamine - Glutamate - ketoglutarate
GIve two examples of amino acid clinical problems
Phenylketonuria: Phenylalanine - tyrosine, using phenylalnine hydroxylase. High phenylalanine causes mental retardation by inhibitin mitochondrial metabolism. Detected in urine, or heel prick of new borns.
Homocystinuria: Homocysteine - Cystathionine, by cystathionine beta synthase. High homosysteine ddamages connective tissue, CNS, muscle.
What are the two ways of processing ammonia and transporting it in the blood
Glutamate + ammonia = glutamine in tissues safe to transport in blood, used in liver to convert to urea or excreted in kidneys
Pyruvate + ammonia = alanine
What are the advantages of urea?
Non toxic, metabolically inert, high nitrogen content, soluble, chemically inert
What is the urea cycle inputs
glutamate and aspartate
what are the dangers of ammonia
extremely toxic to brain, readily dissolvable, alters pH, effects Kreb’s cycle, metabolism
What is refeeding syndrome
When patients are severly malnourished, they have insufficient protein and exnzymes to process amino acids into safe urine. Consequently ammonia levels increase severely. This can cause death, BMI
Give uses for 5 amino acids
Histidine - histimine Cystein - glutathione Arginine - nitric acid Glycine - hae Tyrosine - Thyroid hormones
describe glucagon and its effects
29 amino acids in length, produced by alpha cells in the pancrease, no dsulphde bridges, amino acid hormone
increases glycogenlysis, gluconeogenesis, ketogenesis, lipolysis
inhibits lipogenesis
What are the three regions of the adrenal cortex and their products
zona glomerulosa - mineralcorticcoids - salts Na+/K+, aldosterone
zona fasciculata - glucocorticcoids - sugars, cortisol
zona resticularis - androgens - glucocorticoids testosterone
Describe the adrenal cortex axis
1- hypothalamus detects pain, heat, emotion releases CRF corticotropin releasing factor
2- anterior pituitary responds by releasing 29 aa Adrenocorticotropic Hormone (from POMC)
3 - ACTH reacts with receptors on zona fasiculata and reticularis of the the adrenal gland
4, stimulates cholesterol esterase, producing cortisol
What are the effects of cortisol
increase proteolysis, glycogenlysis, gluconeogenesis, lipolysis
decrease glucose absorption in blood by blocking GLUT4
Stress hormone, increases metabolites
What are the catecholamines
adrenal hormones from the medulla, a modified symptathetic ganglion
What are the effects of adrenaline and where is it synthesised from
increase CNS, cardiovascular, glycogenlysis, lipolysis
Origin is tyrosine
What is Addion’s disease
low cortisol - lethargy, postural hypotension, low glucose, low
In some case ACTH may be expressed at high level without stimulating cortisol but causing pigmentation of the skin. Melanocyte Stimulating Hormone MSH, is part of the ACTH
What is Cushing’s disease
Chronic high coritsol - moon face, buffalo hump, hypertension, striae, muscle wasting in the limbs, mood swings. Cortisol causes redistribution of fat in body.
caused excess ACTH, cortisol or external steroid influence
What is exogenous cushing’s and an example of a causative
A source of steroid that mimics the effects of elevated cortisol taken. Often anti-inflammatory drugs fro arthritis, asthma, inflammatory bowel disease
eg. dexamethasone /Prednisolone
How do you diagnose Cushing’s
Look at natural ACTH and cortisol cycle. Test reaction to anacthen (ACTH analogue) and dexamethosone (cortisol analogue)
What are the two types of cells in the thyroid
follicular cells - T3/T4
parafollicular cells - calcitonin
How is T3 and T4 created
Tysoine is taken into follicular cells
Converted into thyroglobulin
Thyroglobulin is sereted into the colloid of the cell
Iodinating species are also concentrated in the colloid
Iodination of thyroglobulin creates Mono iodotyrosine or Di-iodotyrosine (MIT and DIT). Form together to make T3 and T4
How is coritsol spread around the body
transcortin, overcomes hydrophobic nature of crotisol. Cortisol crosses cell membrane and enters the nucleus
What stimulus produces T3 and T4
stress and temperature, causes hypo to release thyrotropin releasing hormone TRH, which stimulates ant pit to release thyroid stimulating hormone TSH
What are the characteristics of TRH and TSH
TRH is a tri-peptide hormone
TSH is a glycoprotein, 2 sub-units
How are T3 and T4 transported
thyronine binding globulin, albumin, pre-albumin. When bound to the carrier, it is not biologically active.
What are the metabolic effects of T3 and T4
General increase in metabolism across the body. Increase BMR, glucose uptake, lypolysis, protein metabolism, heat production, bone production
How do T3 and T4 work
Directly effect the DNA of the cell, receptos have a greater affinity for T3 than T4. Ratio of 1:10. Generally increase metabolism
Describe Hashimoto’s Disease
1% of population - destruction of thyroid follicular cells, espcially TSH receptors. Symptoms - lethargy, mood swings, cold intolerance, constipation, brittle skin, ataxia
Describe consequences of low thyroid hormone in childhood
Cretinism - lack of thryoid hormone, leads to large tongue, pronounce brown, poor eyes, short stature and mental retardation. Effects neural development in children
Causes of hypothyroidism
destruction of thyroid gland, congenital defect, lack of TSH, lack of iodine
Describe Hyper thyroidism
Grave’s disease - 1% population, autoimmune disease, antibody constantly stimulates TSH receptor. Thyroid stimulating immunoglobulin. Syptoms- high heat, bulging eyes, tachycardia, rapid bowel movements, weight loss.
What is the treatment of hyperthyroidism
carbimazole inhibits thyroglobulin, radioactive iodine obliterates thyroid, surgical removal of the thyroid
What are the functions of the parathyroid gland
Regulate calcium serum levels closely between 1-1.3mol / L
What regulates serum calcium levels
parathyroid hormone PTH, vitamin D, calcitonin
What are the symptoms of hypocalaemia
Hyperexcitability, tetany, paralysis, convulsions
What are the symptoms of Hypercalcaemia
kidney stones, constipation, depression, tiredness
How can tumours effect calcium levels
Common breast and pancreatic tumours release PTHrP - parathyroid hormone related peptide
What are the differences between PTH and Vitamin D (calcitrol) effects on calcium.
Both increase osteoclasts to release calcium from bone hydroxy apatite
PTH stimulates Vit D to increase Ca uptake in the gut
PTH increases reabsoption of Ca in kidneys, Vit D increases reabsorption of Ca and K in kidneys.
PTH increases blood Ca, Vit D increases serum Ca and K
What is Ricket’s
A deficiency in dietary Ca leading to Ca serum levels maintained at the expens of bone. Symptoms - bony necklace, bow legs, soft kull, lumpy joints
Where is Ca absorbed
In the gut, jejunum and ileum mainly, chaperoned across gut epithelia by the Vit D
What are the three regions of the adrenal cortex and their products
zona glomerulosa - mineralcorticcoids - salts Na+/K+, aldosterone
zona fasciculata - glucocorticcoids - sugars, cortisol
zona resticularis - androgens - glucocorticoids testosterone
Describe the adrenal cortex axis
1- hypothalamus detects pain, heat, emotion releases CRF corticotropin releasing factor
2- anterior pituitary responds by releasing 29 aa Adrenocorticotropic Hormone (from POMC)
3 - ACTH reacts with receptors on zona fasiculata and reticularis of the the adrenal gland
4, stimulates cholesterol esterase, producing cortisol
What are the effects of cortisol
increase proteolysis, glycogenlysis, gluconeogenesis, lipolysis
decrease glucose absorption in blood by blocking GLUT4
Stress hormone, increases metabolites
What are the catecholamines
adrenal hormones from the medulla, a modified symptathetic ganglion
What are the effects of adrenaline and where is it synthesised from
increase CNS, cardiovascular, glycogenlysis, lipolysis
Origin is tyrosine
What is Addion’s disease
low cortisol - lethargy, postural hypotension, low glucose, low
In some case ACTH may be expressed at high level without stimulating cortisol but causing pigmentation of the skin. Melanocyte Stimulating Hormone MSH, is part of the ACTH
What is Cushing’s disease
Chronic high coritsol - moon face, buffalo hump, hypertension, striae, muscle wasting in the limbs, mood swings. Cortisol causes redistribution of fat in body.
caused excess ACTH, cortisol or external steroid influence
What is exogenous cushing’s and an example of a causative
A source of steroid that mimics the effects of elevated cortisol taken. Often anti-inflammatory drugs fro arthritis, asthma, inflammatory bowel disease
eg. dexamethasone /Prednisolone
How do you diagnose Cushing’s
Look at natural ACTH and cortisol cycle. Test reaction to anacthen (ACTH analogue) and dexamethosone (cortisol analogue)
What are the two types of cells in the thyroid
follicular cells - T3/T4
parafollicular cells - calcitonin
How is T3 and T4 created
Tysoine is taken into follicular cells
Converted into thyroglobulin
Thyroglobulin is sereted into the colloid of the cell
Iodinating species are also concentrated in the colloid
Iodination of thyroglobulin creates Mono iodotyrosine or Di-iodotyrosine (MIT and DIT). Form together to make T3 and T4
How is coritsol spread around the body
transcortin, overcomes hydrophobic nature of crotisol. Cortisol crosses cell membrane and enters the nucleus
What stimulus produces T3 and T4
stress and temperature, causes hypo to release thyrotropin releasing hormone TRH, which stimulates ant pit to release thyroid stimulating hormone TSH
What are the characteristics of TRH and TSH
TRH is a tri-peptide hormone
TSH is a glycoprotein, 2 sub-units
How are T3 and T4 transported
thyronine binding globulin, albumin, pre-albumin. When bound to the carrier, it is not biologically active.
What are the metabolic effects of T3 and T4
General increase in metabolism across the body. Increase BMR, glucose uptake, lypolysis, protein metabolism, heat production, bone production
How do T3 and T4 work
Directly effect the DNA of the cell, receptos have a greater affinity for T3 than T4. Ratio of 1:10. Generally increase metabolism
Describe Hashimoto’s Disease
1% of population - destruction of thyroid follicular cells, espcially TSH receptors. Symptoms - lethargy, mood swings, cold intolerance, constipation, brittle skin, ataxia
Describe consequences of low thyroid hormone in childhood
Cretinism - lack of thryoid hormone, leads to large tongue, pronounce brown, poor eyes, short stature and mental retardation. Effects neural development in children
Causes of hypothyroidism
destruction of thyroid gland, congenital defect, lack of TSH, lack of iodine
Describe Hyper thyroidism
Grave’s disease - 1% population, autoimmune disease, antibody constantly stimulates TSH receptor. Thyroid stimulating immunoglobulin. Syptoms- high heat, bulging eyes, tachycardia, rapid bowel movements, weight loss.
What is the treatment of hyperthyroidism
carbimazole inhibits thyroglobulin, radioactive iodine obliterates thyroid, surgical removal of the thyroid
What are the functions of the parathyroid gland
Regulate calcium serum levels closely between 1-1.3mol / L
What regulates serum calcium levels
parathyroid hormone PTH, vitamin D, calcitonin
What are the symptoms of hypocalaemia
Hyperexcitability, tetany, paralysis, convulsions
What are the symptoms of Hypercalcaemia
kidney stones, constipation, depression, tiredness
How can tumours effect calcium levels
Common breast and pancreatic tumours release PTHrP - parathyroid hormone related peptide
What are the differences between PTH and Vitamin D (calcitrol) effects on calcium.
Both increase osteoclasts to release calcium from bone hydroxy apatite
PTH stimulates Vit D to increase Ca uptake in the gut
PTH increases reabsoption of Ca in kidneys, Vit D increases reabsorption of Ca and K in kidneys.
PTH increases blood Ca, Vit D increases serum Ca and K
What is Ricket’s
A deficiency in dietary Ca leading to Ca serum levels maintained at the expens of bone. Symptoms - bony necklace, bow legs, soft kull, lumpy joints
Where is Ca absorbed
In the gut, jejunum and ileum mainly, chaperoned across gut epithelia by the Vit D
