Metabolism Flashcards
(300 cards)
0
Q
What is metabolism?
A
The process that derives energy and raw materials from food stuffs to use to support REPAIR, GROWTH and ACTIVITY of the tissues of the body.
1
Q
What is catabolic metabolism?
A
- The break down of molecules to release energy.
- Reducing power
2
Q
What’s anabolic metabolism?
A
The use of energy to make molecules for growth and repair.
3
Q
What does exergonic mean?
A
Energy released > Energy used
4
Q
What does endergonic mean?
A
Energy used > Energy released
5
Q
What are the key components of the diet?
A
- Protein
- Carbohydrates
- Fat
- Water
- Fibre
- Vitamins and minerals
6
Q
For the key components of the diet name what their roles are:
(Protein, carb, water, fibre, fat, nutrients and minerals)
A
- energy and amino acids
- energy
- hydration
- GI function
- energy and fatty acids
- essential
7
Q
Name the essential nutrients and minerals.
A
Minerals: Na, K, Ca, Mg, Cu
Nutrients:
- A,K,D,E (fat soluble)
- B and C (water soluble)
8
Q
The nutrients in the blood are taken to tissues for what uses?
A
- Utilisation
- Storage
- inter-conversion
9
Q
What materials do cells produce for the blood?
A
Clotting proteins
Waste products to excrete (e.g. Respiration)
10
Q
Why may some products vary in concentration in the blood?
A
- Variable usage depending on situation.
- Supply from nutrients vary
11
Q
What are the nutrients and waste products in the blood plasma?
A
- Glucose
- Amino acids
- Fatty acids
- Triacylglycerides
- Cholesterol
12
Q
What are the factors affecting basal metabolic rate?
A
Surface area Gender Environmental temp Body temp (e.g. Fever) Endocrine (thyroid/reproductive hormones)
13
Q
Calculate the BMI of a 90kg person of height 6’1”
And what does it mean?
A
Mass/height^2
90/1.825^2 = 27
Which means he is overweight (27>25)
14
Q
What are the co-morbidities associated with obesity?
A
- Type 2 diabetes
- hypertension
- Cancer
- Gall bladder disease
- CVS disease
15
Q
What are the potential problems with malnutrition?
A
- Nutrient deficiency diseases
- Low energy intake damage
- Low protein levels: changes osmotic pressure of the blood.
16
Q
How does a low protein intake effect the cardiovascular system?
A
Low protein means there’s a higher water potential inside the capillaries, so less water is absorbed back so oedemas form due to the excess water content of the interstitial fluid.
17
Q
What is homeostasis?
A
The maintenance of the internal environment.
18
Q
If homeostasis were to fail what would it lead to?
A
Disease
19
Q
What are the products of catabolic metabolism?
A
- Organic precursors (e.g. Acetyl CoA)
- Building block materials
- Biosynthetic reducing power (NADPH)
- Energy for cell function
20
Q
Energy is produced in metabolism, what is it used for?
A
- Biosynthetic work (synthesis of cellular components)
- Transport system across membranes
- Specialised functions.
21
Q
When a reaction has a delta G value < 0 it is said to be what 2 things?
A
Exergonic and spontaneous.
So the opposite is true…
22
Q
Name the 3 main H carriers.
A
NAD
NADP
FAD
23
Q
What are the carriers of reducing power for:
1) ATP synthesis
2) Biosynthesis
A
1) NADH
2) NADPH
24
Show the reaction of ATP hydrolysis and why does this provide a large amount of energy?
ATP ---> ADP + Pi
| The hydrolysis is a highly exergonic reaction
25
Why is ATP only a carrier of energy?
- It is only stable enough to carry energy for a few seconds.
- It is stable in the absence of specific catalysts.
26
Name the four high energy signals and what do they do?
- ATP
- NADH
- NADPH
- FAD2H
- They activate the anabolic metabolism pathway.
27
When cells need a store of energy but still need it immediately, what is used? Outline the reaction.
Creatine phosphate (phosphocreatine)
Creatine kinase
Creatine ----------> Phosphocreatine
ATP --> ADP
28
How can Creatine kinase be a marker of MI?
Cells undergoing MI release more CK into the blood. So after a few hours the blood concentration of CK is high.
29
What is the general formula for carbohydrates?
| And what types of groups are there?
(CH2O)n
| Keto and aldehyde group.
30
Which type of isomer is present when it's a natural protein?
D Isomer
31
Name two properties of carbohydrates.
- Hydrophilic
| - Partially oxidised (needs less oxygen to oxidise)
32
What is the significance of an enzyme with a beta bond?
It can't be broken down by natural digestive enzymes.
| Apart from lactose
33
Name 3 polysaccharides linked by glycosidic bonds:
- Glycogen (Highly branched)
- Cellulose (Can't be digested as beta 1-4 bond can't be broken)
- Starch (Mix of amylose and amylopectin)
34
Name the two methods of absorption of monosaccharides.
- Facilitated diffusion using transport proteins
| - Active transport
35
What does the blood glucose concentration need to be maintained as?
~5mMol
36
Name 4 tissues that absolutely require glucose.
RBC, kidney medulla, WBC and lens of the eye.
37
What is glycolysis' 3 main functions?
- Oxidise glucose/NADP production
- Synthesis of ATP
- C6 and C3 intermediates
38
Name 3 features of glycolysis.
- Exergonic
- Oxidative
- Anaerobic
39
Write the equation for glycolysis.
Glucose + 2Pi + 2ADP + 2NAD
----->
2Pyruvate + 2ATP + 2NADH + 2H+ + 2H2O
40
Why is glycolysis made up of multiple, smaller steps?
- Efficient energy conversion
- Easier
- Versatility
- Controllable
41
What role does glycerol phosphate have in glycolysis?
- Triacylglyceride and phospholipid biosynthesis.
42
How is glycolysis regulated?
- Allosterically (catalytic and regulatory sites)
| - Covalently ((de)phosphorylation)
43
What would happen if NAD isn't regenerated from NADH during glycolysis?
Product inhibition.
44
Normally NAD is regenerated in stage 4 of glycolysis, however RBC don't have this stage, so how do they regenerate NAD, show the equation:
Pyruvate + H+ + NADH -----> NAD + lactate
Via the enzyme LDH: lactate dehydrogenase
45
What 3 things does lactate concentration in the blood depend on?
- Production
- Utilisation (liver, heart, muscle)
- Disposal (Kidneys)
46
When is lactate produced?
- Strenuous exercise
| - Psychological situations (shock/congestive heart disease)
47
How is lactate important?
- Used in heart muscles
- Gluconeogenesis
- Impaired liver disease
48
What are the clinical conditions associated with fructose?
- Fructosuria (Fructose can't go to F-1-P, absence of fructokinase)
No symptoms only high levels in urine
- Fructose intolerance (No aldolase so accumulation of F-1-P)
Liver damage, treatment = remove fructose from diet.
49
How does cataracts occur from galactosaemia?
Glucose -----> Galactitol
NADPH ---> NADP
- So NADPH levels are depleted, structural damage occurs as s-s bonds form, forming cataracts.
Treatment: remove lactose from the diet.
50
Outline the two stages of the Pentose phosphate pathway.
1) oxidative decarboxylation
G-6-P ----> 5C sugar + CO2
NADPH --> NADP
2) Rearrangement to glycolytic intermediates
3,5C sugars ----> glyceraldehyde + 2fructose.
51
What are the features of the PPP?
- No ATP production
- Irreversible: loss of CO2
- Controlled by NADPH/NADP ratio at G-6-P stage
52
What are the functions of the PPP?
- NADPH production
(Prevent S-S bonds forming & reducing power)
- Produces 5C sugars
(For nucleotides needed in nucleic acid)
53
How is G6PDH a problem?
Decrease is NADPH concentration so proteins are oxidised (s-s bonds form)
So the structure of the proteins change, causing their function to change.
So the PPP keeps proteins reduced.
54
Outline the reaction to form Acetyl CoA from Pyruvate.
And why is he reaction irreversible?
Pyruvate + CoA + NAD = Acetyl CoA + CO2 + NADH + H+
Loss of CO2
55
What is PDH sensitive to?
Vitamin B1 deficiencies.
56
What's the TCA reaction equation and where does it occur?
- Acetyl CoA + 3NAD + FAD + 2H2O + Pi + GDP
- -> 2CO2 + 3NADH + FAD2H + GTP + CoA + 3H+
- Mitochondria
57
How is the TCA cycle regulated?
Activated by ADP
| Inhibited by NADH
58
What is electron transport?
Electrons on NADH and FAD2H are transported by a series of carrier molecules to oxygen.
59
What is oxidative phosphorylation?
- Electrons transferred from NADH and FAD2H to molecular O2
- Energy released is used to generate a proton gradient and so PMF
- Energy from dissipation of PMF is used for the synthesis of ATP from ADP
60
What is PMF?
Proton motive force: the hydrogen concentration across the inner mitochondrial membrane.
61
What inhibits oxidative phosphorylation?
CO and CN, competitively with a high affinity
62
What's an uncoupler?
- Increases the permeability of the inner mitochondrial membrane to protons.
- dissipates the H+ ions so the PMF reduces.
- No drive for ATP synthesis.
63
Brown adipose tissue is found where and to what use?
- Newborn infants, to maintain heat around the vital organs.
| - Hibernating animals, to generate heat.
64
What's the difference between oxidative and substrate phosphorylation?
Substrate: soluble enzymes, coupling by high energy hydrolysis, can work in limited O2.
Oxidative: needs membrane associated complexes, coupling by PMF, cannot work without O2.
65
What are the 4 classes of lipids?
- Ketone bodies
- Fatty acids
- Triglycerides
- Vitamins
66
Where does FA catabolism occur?
Mitochondria
67
How is FA synthesis activated?
| What problem is there with that?
Linking to Acyl CoA
| Acyl CoA molecule is with Acyl too large to cross membrane.
68
Name and outline the mechanism that allows for FA to cross inner mitochondrial membranes.
- Carnitine shuttle.
- Acyl CoA -> CoA which using CAT1 adds Acyl to carnitine.
- Acyl carnitine can pass through the membrane. The reverse occurs on the other side of the membrane using CAT2.
- Acyl group has passed through the membrane
- FA is resynthesied inside the membrane.
69
Is more energy derived from FA oxidation or glucose oxidation?
FA oxidation
70
What are the three types of ketone bodies?
- Acetoacetate
- Acetone
- B-Hydroxybuterate
71
Where are ketone bodies synthesised and under what chemical conditions?
- Liver
| - Low insulin to glucagon ratio (starvation/diabetes)
72
Fill in:
Acetyl CoA ---> X ---> W
Insulin (fed state)
Acetly CoA ---> X ----> Y
Z (starvation)
- X = HMG CoA
- W = Cholesterol
- Y = Ketone bodies
- Z = Glucagon
73
What is the blood glucose value?
5mM
74
Why is glycogen a good way of storing glucose?
- Large molecule, so efficient.
| - Minimal osmotic effect
75
What are the 4 equations of glycogenesis?
- Glucose + ATP ---> G-6-P + ADP
Hexokinase
- G-6-P -----> G-1-P
Phosphoglucomutase
- G-1-P + UTP + H2O ---> UDP-Glucose + 2Pi
- Glycogen (n) + UDP-glucose ----> Glycogen (n+1) + UDP
Glycogen synthase
76
When does glycogenolysis occur?
- In the skeletal muscles in response to exercise
| - In the liver in response to fasting or stress
77
Outline the 3 steps of glycogenolysis
Glycogen ---> Glucose-1-P ----> Glucose-6-P -----> Glucose
1) . 2). 3).
1) Glycogen phosphorylase
2) Phosphoglucomutase
3) Glucose-6-Phosphatase
78
What is 1) Glycogen synthesis regulated by?
| 2) Glycogen degradation regulated by?
1) Glycogen synthase
| 2) Glycogen phosphorylase
79
In glycogen regulation what occurs when there's an excess/diminished amount of glycogen?
- Excess = tissue damage
| - Diminished = hypoglycaemia / poor exercise tolerance
80
What is Gluconeogenesis and where does it occur?
- The production of glucose from non-carbohydrate precursors.
- Liver & Kidney cortex
81
When does Gluconeogenesis occur?
- Starvation/fasting
- Prolonged exercise
- Stress
82
What enzymes stimulate/inhibit Gluconeogenesis?
Stimulate: High levels of PEPCK and fructose 1,3 bisphosphatase
Inhibit: Low levels of PEPCK and fructose 1,3 bisphosphatase
83
What is needed in FA synthesis?
Where does is occur?
- NADPH
- ATP
- Cytoplasm
84
How is Acetyl CoA transported into the cytoplasm?
Acetyl CoA + oxaloacetate = citrate
Citrate can be transported into the cytoplasm
Citrate -> Acetyl CoA + oxaloacetate
85
What is the overall equation for lipogenesis?
Acetyl CoA + 7ATP + 14NADPH + 6H+ -------> Triglyceride + 7ADP + 14NADP + 6H2O + 8CoA + 7Pi
86
For lipogenesis what is the multi-enzyme complex used?
Fatty acid synthase
87
What is the difference between FA oxidation and FA synthesis?
Oxidation: mitochondrial, glucagon and adrenaline stimulate, insulin inhibits.
Synthesis: Cytoplasm, glucagon and adrenaline inhibits, insulin stimulates.
88
What regulates lipolysis?
- Adrenaline and glucagon activates
| - Insulin inhibits
89
When would a positive N balance occur?
- Pregnancy
| - Growth
90
When would a negative N balance occur?
- Tissue wasting disease
| - Starvation
91
What are the 8 essential amino acids?
- Lysine
- Isoleucine
- Leucine
- Threonine
- Valine
- Tryptophan
- Phenylalanine
- Methionine
92
Why is -NH2 removed from amino acids?
| And by what two processes?
- Potentially toxic
- Transamination
- Deamination
93
What are the 2 possible reactions for Transamination?
Alpha ketogluterate + amino acid ---> glutamate + Keto acid
Oxaloacetate + amino acid ---> aspartate + Keto acid
94
What are ALT and AST and what do they do?
ALT alanine amino transferase (alanine -> glutamate)
AST aspartate amino transferase (glutamate -> aspartate)
95
How is the NH3 group disposed of?
- Urea
| - Glutamine
96
Name 6 characteristics of urea
- Non toxic
- Inert
- Excreted mainly in urine
- High N content
- Very water soluble
- Useful osmotic effect in kidney tubules
97
Where does the urea cycle occur and how many enzymes does it involve?
- Liver
| - 5
98
What do partial losses in urea related enzymes lead to?
- Hyperammonaemia
99
What clinical signs are there for urea defects?
- Vomiting
- Lethargy
- Irritability
- Mental retardation
- Coma
- Seizures
100
How are urea defects treated?
- Low protein diet
| - amino acids replaced by Keto acids
101
In which 3 ways is ammonia toxic to cells?
- pH effects.
- Reduces TCA cycle, so less energy supply to cells.
- Neurotransmitter synthesis in CNS.
102
What is the normal level of NH4+?
20-40 micro moles.
103
How is NH3 used during detoxification?
- Synthesising Glutamine
| - Then excreted directly or converted to urea.
104
How is Glutamine synthesised?
- Glutamate + ammonia --> Glutamine (ATP required)
105
What is phenylketonuria?
- Autosomal recessive genetic disorder
- disfunction of phenylalanine hydroxylase prevents Tyrosine production and so Noradrenaline/adrenaline/dopamine
- So more phenylpyruvate produced instead.
- So excess in urine.
106
What is homocystinuria?
- Autosomal recessive
- Fibrillin-1's protein structure affected
- No/reduced CBS, so less cystathionine and so cystine produced.
- More methionine with a B12 catalyst produced.
- Elevated plasma homocysteine associated with CV disease
107
What and how are Arginine and Cystine affected by gas signalling molecules?
- Arginine: NO, vasodilator, neurotransmitter, inflammatory mediator
- Cysteine: H2S, ^,^,^.
108
What are the 5 different classes of lipids?
- Triacylglycerides
- Fatty acids
- Cholesterol
- Cholesterol esters
- Phospholipids
109
What role does cholesterol have in the body?
- Major component of membranes
| - Precursors to steroid hormones and bile acids
110
How is cholesterol made?
- Synthesised in the liver
| - Found in diet
111
What are phospholipids and what role do they play?
- Diacylglycerol with a phosphate group.
- Major component of membrane
- Phospholipid bilayer.
112
How are lipids transported in the bloodstream?
- Proteins: albumin/lipoprotein particles
| - Micelles (hydrophilic outer layer with apoproteins and a hydrophobic centre)
113
Why do different classes of lipids have to have specific apoproteins?
- Function: Activation of enzymes, recognition of cell surface receptors
114
What are the different classes of lipoprotein particles?
- Chylomicrons
- VLDL
- LDL
- HDL
115
How are Chylomicrons formed and where?
- By enterocytes lining the intestine.
116
What are the roles of chylomicrons?
- Reformation of triacylglycerides from food with specific apoproteins
- Carries lipids from the diet to tissues (especially adipose)
117
When are chylomicrons found?
- 4-6 hours after a meal
118
What does VLDL, LDL and HDL stand for?
- VLDL: Very low density lipoproteins
- LDL : Low density lipoproteins
- HDL: High density lipoproteins
119
Where are VLDLs produced and what is its role?
- Liver
- Storage of energy by combining apoproteins and triacylglycerides.
- Transport lipids from the liver to tissues when needed.
120
What is the role of LDLs
Transport liver cholesterol and apoproteins to tissues.
121
Why is having a high level of LDLs dangerous to your health?
- Cholesterol rich
| - Increases the risk of atherosclerosis.
122
Where are HDLs formed, how and what do they do?
- Formed in tissues
- Cholesterol from tissues + apoproteins
- Carries excess cholesterol from tissues to liver.
123
How are triacylglycerides transferred from chylomicrons to VLDL?
- Chylomicrons and VLDL bind
- Lipase from endothelial cells of capillaries cleaves triglycerides into glycerol (remains in circulation) and FA (goes to tissues for metabolism)
124
After the transfer of triacylglycerides from chylomicrons to VLDL what happens to the VLDL remnants?
- Removed by liver/converted to other types of lipoproteins.
125
How does the transfer of cholesterol from LDLs occur?
- LDL receptors on cells
- Complex proteins bind to LDL and taken into cells by endocytosis
- Cholesterol ester released and LDL cleaved into cholesterol and FA
- Uptake stimulated by need
126
How are HDLs formed?
- Nascent HDL (HDL shells) are synthesised
- Sources from VLDL remnants and cholesterol in capillaries
- Mature into HDL particles.
127
Why may Hyperlipoproteinanaemia occur?
- Defective enzymes
- Defective receptors
- Defective apoproteins
128
What is Hyperlipoproteinanaemia?
- Raised levels of one or more lipoprotein classes.
| - Caused by over production/under removal.
129
How does an atheroma form?
- Oxidation of LDLs -> macrophages produced -> Foam cells -> accumulation in interior of b.v walls -> Fatty streak -> Atheroma
130
What are the treatments for Hyperlipoproteinanaemia?
- Reduce cholesterol and saturated lipids in the diet
- Increase exercise
- Stop smoking
- Statins
131
What do statins do?
- Reduce cholesterol synthesis by inhibition of HMG CoA reductase
- Increases expression of LDL receptors in hepatocytes
132
What does ROS stand for?
- Reactive oxygen species
133
How are SOR converted into harmless substances?
SOR ----> H2O2 ----> H2O + O2
| SOD. Catalase
134
How are hydroxyradicals produced?
- UV
- X-Rays
- Gamma radiation
- Are all very damaging to cell membranes, can't be eliminate by an enzyme system
135
What are the cellular defences against NO?
- Glutathione (GSH) SH groups are an antioxidant.
| - Oxidise form has S-S bonds, glutathione disulphide.
136
How is NADPH a cellular defence?
Is an oxidising agent. NADPH ---> NADP
Works against OH radicals
137
Give examples of antioxidants.
- Vitamin C, E, and A
- Flavenoids: polyphenols, beta carotine
- Minerals: selenium, zinc
138
What is oxidative stress?
| What can it cause?
- When the antioxidants are lower than the ROS so they are free to damage cells and interfere with DNA, lipids in cell membranes and proteins.
- Can cause cancer, emphysema, pancreatitis and CV disease.
139
Oxidative stress can lead to lipid peroxidation, what is this?
- ROS reacts with unsaturated lipids to form lipid peroxides
- Damages cell membranes
140
What is an oxidative burst and how can it be useful?
- Rapid release of superoxide and H2O2 from leukocytes
| - Rapid production of ROS kills pathogens in the locality.
141
What is pharmacology? And how is is split?
- 'The study of how chemical agents affect the function of living systems'
- Pharmacokinetics
- Pharmacodynamics
142
What is pharmacodynamics?
- What the drug does to the body
143
What is pharmacokinetics?
| What are the stages?
The study of the time course of drugs and their metabolites in the body.
- Absorption
- Distribution
- Metabolism
- Elimination
144
Why is the property of being lipid soluble in drugs a problem?
- Lipid soluble (not water soluble) can't be excreted by the kidney as they are easily re absorbed into the blood.
145
How does drug metabolism help with excretion of drugs?
- Turns parent drug molecule into a polar, lipid-insoluble, water soluble derivative. (Metabolites)
146
What are the two main roles if drug metabolism?
- Deactivation
| - Elimination
147
What happen in Phase 1 of drug metabolism?
- Oxidation, reduction, hydrolysis
| - Adds/exposes reactive group.
148
What are the main sites of Phase 1 drug metabolism?
- Liver
| - Microsome situated on ER in hepatocytes.
149
What's the main role for Phase 2 metabolism?
- Conjugation (altered drug molecules combined with a water soluble group.
150
What is the enzyme system used for drug metabolism pathways?
- CYP (Cytochrome P450)
151
For Phase 2 of drug metabolism what are the main sites and what reactions occur there?
- Liver, cytosolic enzymes
| - Glucuronidation, sulphate conjugation, glutathione conjugation
152
What is Glucuronidation?
Glucuronic acid + UDP ---> UDPGA
| UDP Glucuronic acid
153
What is polymorphism?
- The individual variation that causes drugs to affect people differently.
154
What is pharmacoepidemiology?
- The study of drug effects in large populations
155
What is pharmacovigilance?
- The reporting of adverse drug reactions post-marketing.
156
What environmental factors have an effect on drug metabolism?
- Enzyme inhibition
| - Enzyme induction: metabolism of on agent induces enzymes in the liver which increases the metabolism of other drugs.
157
What occurs to the Phase 2 pathway when a toxic dose of paracetamol has been taken?
- It becomes saturated
158
What happens to the Phase 1 pathway when a toxic dose of Paracetamol has been taken?
- It produces NAPQ1 from the paracetamol which then undergoes phase 2 metabolism = glutathione conjugation
159
What is the treatment for an overdose of paracetamol?
- N Acetyl cysteine (antioxidant)
160
What is the role of alcohol dehydrogenase?
- Converts alcohol to acetaldehyde (toxic metabolite)
- Ethanol ------> acetaldehyde
NAD ---> NADH + H+
161
What are the recommended alcohol units for men and women?
- Men 21 units (4 units over 5 days)
| - Women 14 units (3 over 5 days)
162
What are the effects of chronic alcohol toxicity?
- Excess NADH simulates fat deposition
- Acetaldehyde damages liver cells ---> 'fatty liver'
- Alcoholic hepatitis and cirrhosis
163
What is the treatment for chronic alcohol toxicity?
- Disulfiram (aldehyde dehydrogenase inhibitor)
164
What are the different types of communication in control systems?
- Nervous (action potential)
- Endocrine (hormones)
- Paracrine (local hormones)
- Autocrine (many agents)
165
Outline the receptor - effector loop.
Stimulus -> Sensor -> Signal AFFERENT pathway -> Control centre -> Signal EFFERENT pathway -> Effector
166
What is a negative feedback loop? And where is it found?
- Effector opposes stimulus
| - Most hormonal control systems
167
What is a positive feedback loop and where are they found?
- Stimulus produces an increase in effect
- 'Catastrophic change'
- Ovulation
168
How does the biological clock work?
- Suprachiasmatic nucleus in hypothalamus
| - Melatonin is released from pineal gland in the light/dark cycle.
169
What are the total body water percentages in an adult male and female?
- Male 50-60%
| - Female 45-50%
170
How many litres of water are there in a 70kg male?
And how many litres of water are there in:
- Intracellular fluid
- Extracellular fluid
- Blood plasma
- 42 Litres
- 28 Litres
- 9.4 Litres
- 4.6 Litres
171
How is the water concentration in the blood plasma maintained?
- Increase in osmolality of blood plasma ---> release of anti diuretic hormone (ADH) from posterior pituitary gland ---> Increase in Reabsorption of H2O from urine into blood in collecting ducts in the kidney ---> Decreased osmolality of blood plasma.
172
How is osmolality and Na+ concentrations monitored?
- Osmoreceptors in hypothalamus
173
Why do endocrine hormones only affect certain cells?
The hormones only interact with cells with receptors?
174
How are endocrine hormones released?
- Hypothalamus produces releasing factors
- Stimulates the anterior pituitary gland (mast gland) to release trophic hormones
- Endocrine glands are stimulated by the trophic hormones
175
What does HPA stand for in HPA axis?
- Hypothalamic pituitary adrenal.
176
Outline the HPA axis.
- Hypothalamus produces carticotrophin releasing hormone
- Anterior pituitary detects, releases ACTH (adrenocarticotrophic hormone) via the blood
- Adrenal cortex detects, releases Cortisol
177
How are hormone secretions controlled?
- By other hormones or itself.
178
What type of hormones are water soluble and which are not?Z
- Water soluble: Peptide and amine
| - Not water soluble: steroid and thyroid
179
How are non water soluble hormones transported in the blood?
- Carrier proteins
- Increase solubility of hormone in plasma
- Increase in half life
- Readily accessible reserve
180
When are hormones biologically active?
- When in the free form.
181
What are the different classes of hormones?
- Polypeptide
- Glycoproteins
- Amino acid derivatives
- Steroid hormones
182
Give examples of polypeptide hormones.
- It's the largest group (20)
- Growth hormone
- Insulin
183
Give examples of glycoprotein hormones.
- Thyroid stimulating hormone
- LH
- FSH
- Human chorionic gonadotrophin
184
Examples of amino acid derivatives.
- Tyrosine
- Thyroid hormones, T4 & T3
- Adrenaline
- Histamine from histidine
- 5-hydroxytryptamine (5-HT) from tryptophan
185
Give examples of steroid hormones and what are they derived from?
- Derived from Cholesterol
- C27- calciterols
- C21- corticosteroids
- C19- Androgens
- C18- Oestrogen
186
How do hormones act?
- By binding to receptors on/in target cells
187
What does the magnitude of hormone effect depend on?
- Concentration of active hormone
- Receptor number
- Affinity of hormone for receptor
- Degree of signal amplification
188
How does a hormone effect a target cell if it can't cross the cell membrane?
- Binds to receptor on cell surface
- Activates 2nd messenger pathway
- 2nd internal messenger exerts metabolic effects.
189
How can steroid hormones cross cell membranes?
- Lipid soluble (cholesterol derivatives)
190
What part of the hypothalamus controls appetite?
- Appetite/Satiety centre (arcuate nucleus)
191
In the arcuate nucleus what are the roles of the primary and secondary neurones?
- Primary: sense glucose, FA in blood, response to hormones
| - Secondary: synthesise input, co-ordinate a response
192
How come primary neurones are able to detect hormones?
- No blood brain barrier.
193
Outline the excitatory pathway from primary neurones for appetite.
- NPY, Neuropeptide Y
- AgRP, Agouti-related peptide
- These stimulate appetite.
194
Outline the inhibitory pathway for appetite.
- Pro-opiomelanocortin (POMC)
- Beta-endorphin leads to a reward system when full.
- Alpha-melanocyte stimulating hormone. (@-MSH) suppresses appetite.
195
What hormones feedback to the hypothalamus from the gut and what do they do?
- Ghrelin: peptide released from wall of stomach when empty.
stimulates excitatory neurones in arcuate nucleus
Filling stomach inhibits Ghrelin
- PYY: peptide hormone released from wall of small intestine.
suppresses appetite
196
What hormones are responsible for feedback from the body to the hypothalamus, for appetite?
- Leptin: released from adipocytes
stimulates inhibitory neurones in arcuate nucleus
suppresses appetite
induces expression of uncoupling proteins in mitochondria.
- Insulin: surprises appetite (same as above, not as important)
- Amylin: peptide hormone
secreted from beta cells in pancreas, surpresses appetite
197
What is metabolic syndrome?
- Insulin resistance
- Dyslipidaemia
- Impaired glucose tolerance
- Hypertension
- 12-25% affected in developed countries.
198
What is foetal programming?
- Foetus adapts to conditions in utero e.g supply of nutrients.
- Biochemical adaptions become 'programmed' in pre-disposing to adult disease conditions.
199
What is epigenetics?
- Inherited phenotype resulting from changes in chromosomes without changes in DNA sequence.
200
Outline some characteristics of Type 1 diabetes and who it commonly affects
- Insulin deficiency
- Can be autoimmune or non-autoimmune
- Destruction of beta cells.
- Younger people (less than 30yrs)
201
Outline some characteristics of Type 2 diabetes and who it commonly effects.
- Insulin deficiency and resistance
| - Obese people who are older (normally)
202
What are the common symptoms of diabetes mellitus?
- Polyuria (high glucose conc in urine, needing to go all the time as glucose has an osmotic effect)
- Polydipsia (thirsty all the time)
- Blurring of vision
- Urogenital infections (thrush)
- Inadequate energy utilisation (tiredness, weakness, lethargy, weight loss)
203
What does the severity of the diabetes depend on?
- Rate of rise of blood glucose
| - Absolute levels of glucose.
204
Name 4 types of diabetes diagnosis test and their criteria
- 1) Fasting venous plasma glucose: (>7mmol/l)
- 2) Random ^ : (>11.1mmol/l)
- 3) HbA1c: (>6.5%)
- 4) Oral glucose tolerance test (1&or 2)
205
What are the specific symptoms typical of type 1 diabetes?
- Rapid onset: weight loss, Polyuria, Polydipsia
- Late presentation: vomiting due to ketoacidosis (only found in type 1)
- Too late: coma/death
206
What is the diagnostic tool to detect the presence of ketones?
- ketostik
| - ketones present signifies absolute lack of insulin.
207
What is the treatment of type 1 diabetes?
- Subcutaneous injection several times per day.
208
What are the specific symptoms of type 2 diabetes?
- Absence of ketones in urine (means not type 1)
| - Elevated venous plasma glucose
209
What are the acute complications of diabetes?
- Hyperglycaemia: diabetic ketoacidosis in type 1
hyperosmolar non-ketotic syndrome in type 2
- Hypoglycaemia: Coma
brain needs glucose
210
What are the chronic complications of diabetes?
- Macrovascular: stroke, heart attack, intermittent claudication, gangrene (cerebrovascular, cardiovascular, peripheral vascular disease)
- Microvascular: Blindness, renal replacement therapy, erectile dysfunction, foot ulceration, diarrhoea, constipation, painful peripheral neuropathy. (Retinopathy, nephroopathy, neuropathy)
211
What are the two main functions of the pancreas?
- Production of digestive enzymes, secreted into duodenum (exocrine)
- Hormone production (Islet of Langerhans)
212
Where are Insulin and Glucagon secreted from?
- Insulin = beta cells
| - Glucagon = alpha cells
213
How does blood glucose concentrations in the blood change in the presence of : a) Insulin?
b) Glucagon?
- Insulin decreases by fat cells taking in glucose from the blood
- Glucagon increases by liver releasing glucose into the blood
214
What is the signal, target tissue and action of Insulin?
- Feeding
- Adipose, skeletal, liver
- Anabolic
215
What is the signal, target tissue and action of glucagon?
- Fasting
- Liver, adipose
- Catabolic
216
What conditions can increase/decrease the renal threshold for glucosuria?
- Pregnancy decreases
| - Being elderly increases
217
Give 4 properties of Insulin.
- Glycogenic
- Anti-gluconeogentic
- Anti-lipolitic
- Anti- ketotonic
- Favours storage
218
Outline how insulin is synthesised.
- Insulin mRNA translates to preproinsulin as a precursor.
- Insert into ER -> pro insulin
- Exposed to several specific endopeptidases -> mature insulin (C peptide is excised)
- Insulin and free C peptide are packaged -> Golgi -> secretory granules.
- Accumulates in cytoplasm
- Margination - granules move to cell surface
- Exocytosis
219
How is insulin secreted from beta cells?
- Stimulus = increase in glucose levels
- Glucose -> beta cells by facilitated diffusion via GLUT 2
- Increase in glucose conc in ECF = Increase in beta cells
- Depolarisation of membrane - influx of Ca
- This triggers Exocytosis of insulin-containing secretary granules
220
What does Insulin do in the liver, muscles and adipose tissues?
- Increase in glucose uptake into target cells & glycogen synthesis
- In the liver it stimulates glycogen formation and inhibits breakdown of AA
- In muscles it stimulates uptake of AA promoting protein synthesis
- In adipose tissues it stimulates storage of triglycerides
- Inhibits breakdown of FA
221
Outline the structure of an Insulin receptor.
- Alpha chain on exterior
| - Beta chain spans cell membrane in single segment.
222
Outline how the insulin receptor is activated.
- Alpha chains move together when insulin is detected and folds around insulin- moves beta chains together
- Beta chains form on active tyrosine kinase
- Initiates a phosphorylation cascade resulting in an increase in GLUT 4 expression
- Result - cells can take up more glucose.
223
What are the 5 effects of glucagon?
- Increases Gluconeogenesis (glucose from AA)
- Increases glycogenolysis
- Increases lipolysis to increase FA in the blood
- Overall increase in glucose in blood plasma
- Ketogenesis
224
What are the hormones that are produced by the pituitary gland?
- TSH (thyrotrophs)
- ACTH (corticotrophs)
- GH (somatrophs)
- LH and FSH (gonadotrophs)
- Prolactin (lactotrophs)
225
What hormones does the adrenal gland cortex produce and give examples.
- Mineralocorticoids, aldosterone
- Glucocorticoids, cortisol & corticosteroid
- Androgens, dehydroepiandrosterone
226
What hormone does the adrenal medulla produce?
- Adrenaline
227
Outline the structure of the adrenal cortex?
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
228
What does each section of the adrenal cortex produce and its role?
- Zona glomerulosa: mineralocorticoid, regulate Na and K production
- Zona fasciculata: glucocorticoids, regulation of carb metabolism
- Zona reticularis: glucocorticoids and androgens
229
How are steroid hormones produced? Give a key characteristic.
- Synthesised from cholesterol via progesterone.
| - Lipophilic
230
How is cortisol secretion controlled?
- ACTH from corticoids from anterior pituitary
| - ACTH controlled by CRF in response to physical, chemical and emotional stressors.
231
How do ACTH levels fluctuate during the day?
- Highest in early hours and decreases throughout the day.
232
How does ATCH result in cholesterol esterase production?
- Interacts with high affinity to receptors on Zona fasciculata and reticularis.
233
What are the results of over secretion of ACTH?
- Increased pigmentation due to partial MSH activity
- Adrenal hyperplasia
- Over production of cortisol
234
How is cortisol transported in the blood stream?
- Via plasma proteins as it's Lipophilic
235
How does cortisol act?
- Crosses plasma membrane of target cell and binds to cytoplasmic receptors
- Hormone/receptor complex enters nucleus to interact with specific DNA regions
- Changes rate of transcription of specific genes.
236
What does cortisol cause in response to stress?
- Decreased amino acid uptake, decreased protein synthesis and increased proteolysis in most tissues (not liver)
- Increased hepatic Gluconeogenesis and glycogenolysis
- Increased lipolysis in adipose tissue
- Decreased peripheral uptake of glucose
237
What neurotransmitters does the adrenal medulla produce?
- Noradrenaline
| - Dopamine
238
Outline catecholamine synthesis.
- Tyrosine -> dopamine -> noradrenaline -> adrenaline
239
What effects does adrenaline have on the body?
- Increased cardiac output and blood supply to muscle
- Increased mental alertness
- Increased glycogenolysis in liver and muscle
- Increased lipolysis in adipose tissues
240
What effects are there if there's an over secretion of adrenaline?
- Hypertension
- Anxiety
- Palpitations
- Pallor
- Sweating
- Glucose intolerance
- All due to a tumour.
241
Hypoactivity of the adrenal cortex can be due to what, and what is this also known as?
- Addison's disease
- Autoimmune destruction of cortex reduces glucocortoids and mineralcorticodis.
- Disorders of pituitary/hypothalamus = decrease in ACTH/CRF
242
How does hyperactivity of adrenal cortex occur? And what are the effects?
- Increased secretions of glucocorticoids (Cushing's syndrome)
- Increased activity due to adenoma (tumour)
- Disorders in secretion of ACTH caused by pituitary adenoma or ectopic secretion of ACTH.
243
What is congenital adrenal hyperplasia?
- Genetic defect in enzymes needed for cortisol synthesis
- No feedback to pituitary = no control, ACTH continues to be produced
- Increased ACTH means increase of size of adrenal cortex
244
What are the signs and symptoms of excess cortisol?
- Increased muscle proteolysis and hepatic gluconeogenesis => hyperglycaemia with polyuria and polydipsia (steroid diabetes)
- Thin arms and legs due to muscle wasting
- Increased lipogenesis in adipose tissues and deposition of fat in abdomen, neck and face hence MOONFACE and weight gain
- Purple striae on lower abdomen, upper arms and thighs
- Easily bruised due to thinness of skin
- Acne and bacterial infection susceptibility increase due to immunosuppression
- Osteoporosis
- Hypertension
245
What are the signs and symptoms of too little cortisol?
- Addison's
- Tiredness, extreme muscle weakness, anorexia, vague abdominal pain, weight loss and dissiness
- Increased pigmentation at points of friction, buccaneer mucosa, scars and palmor creases due to ACTH mediated melanocyte stimulation
- Decreased bp. due to Na and fluid depletion
- Hypoglycaemic episodes on fasting
246
When can a crisis occur? And what are the results?
- Stress/trauma/severe infection
| - Nausea, vomiting, extreme dehydration, hypotension, confusion, fever, coma
247
What are the tests for adrenocarticol function?
- 24 hour cortisol free urine
- DST low dose
- ACTH stimulation tests
- Plasma cortisol levels
248
What can over secretion of aldosterone cause?
- Hypertension and muscle weakness
- Increase Na+ reabsorption in kidney in exchange for K+
- Too much exchanges so no K+
249
What are the consequences of over-secretion of adrenal androgens?
- Increased hair growth
- Increased muscle bulk
- Deepening of voice
- Broadening of shoulders.
250
Where is the thyroid gland found?
- Base of neck
- Wraps around trachea below cricoid cartilage
- 2 lobes connected by isthmus
251
What is an enlarged thyroid called?
- Goiter
252
How is thyroid secretion increased?
- Nervous impulse from the sympathetic NS
253
What are the cells that make up the thyroid gland and their structure?
- Colloid cells
- Surrounded by string of epithelium to form follicles
- Darker cells surrounding colloid are C cells
254
What do c cells produce?
- Calcitonin
255
How are thyroid hormones synthesised?
- From tyrosine residues.
256
How are T3 and T4 secretions regulated?
- By Thyroid stimulating hormone from pituitary
- TSH is regulated by TRH (thyrotropin releasing hormone) from hypothalamus
- T3 and T4 cause negative feedback to control levels of TSH and TRH.
257
What does T3 and T4 stand for?
- T3: Tri-iodothyronine
| - T4: Tetra-iodothyronine
258
What are the chronic affects that TSH has on the thyroid?
- Simulates growth and division of follicle cells
| - Gland enlarges to form goitre
259
What are the acute effects TSH has on the thyroid?
- Stimulates storage, synthesis and secretion of T3 and T4
260
What are the differences between T3 and T4?
- T3: more potent, shorter half life, less produced
| - T4: less potent, longer half life, more produced
261
How can T4 be converted into T3?
- Deiodination
262
How are T3 and T4 synthesised?
- Needs iodine from diet
- Follicular cells concentrate iodine using an iodine trap
- Iodine is activated by peroxidase enzyme
- Reactive iodine associates with thyroglobulin
- Protein containing the iodothyronines are stood red as colloid in follicular cells.
263
Why is T4 used to treat hypothyroidism?
- Easier to maintain constant blood conc.
264
What are the standard amounts of free T3 and T4 in the blood?
- T3: ~8 pmol/l
| - T4: ~20 pmol/l
265
What are the effects of thyroid hormones?
- Increased basal metabolic rate (Increase: no. and size of mitochondria, O2 consumption, Nutrient utilisation)
- Stimulates metabolic pathways (catabolic>anabolic)
- Promotes growth and development of tissues
- Increases responsiveness of tissues to SNS (noradrenaline), metabolic and reproductive hormones
266
What effects do thyroid hormones have on the NS?
- Increased myelination of nerve fibres and neurone development
- Increased speed of reflexes
- Increased mental activity
267
What effect do thyroid hormones have on the CVS?
- Increased cardiac output
268
What effect do thyroid hormones have on the skin and subcutaneous tissue?
- Increased turnover of proteins and glycoproteins
269
What can hypothyroidism cause?
- Cretinism in new borns
- Severe muscle retardation (CNS development)
- Coarse features and protruding tongue
- Diminished liver growth
- Delayed sexual development.
270
What are the effects of hyperthyroidism?
- Increased BMR and catabolic activity
- Increased sympathetic and CNS activity
- Reach mental peak earlier in life
271
What are the signs and symptoms of hyperthyroidism?
- Heat intolerance, increased perspiration, warm, moist hands
- Weight loss
- Tachycardia (often irregular) increased cardiac output
- Increased bowel movement and appetite
- Nervousness, irritability, emotional lability
- Exphthalmus (bulging eyes)
- Hyper reflexive
272
What can be the cause of hyperthyroidism?
- Grave's disease
| - Autoimmune: production of antibodies that stimulate TSH receptor on follicle cells
273
Give some treatments for hyperthyroidism.
- Radioactive I2 destroys thyroid and leads to hypothyroidism
- Surgery, risky as easy to remove the parathyroid too
- Carbimazol inhibits iodine incorporation into thyroglobulin.
274
What are the signs and symptoms of hypothyroidism?
- Cold intolerance, decreased perspiration
- Mild weight gain
- Decreased cardiac output
- Mood swings
- Poor concentration
- Oedema and dry, firm, waxy swelling of the skin.
- Brittle nails, hair loss, dry skin.
275
What are the causes of hypothyroidism?
- Hashimoto's
- Autoimmune destruction of thyroid follicles
- Production of antibody blocking TSH receptor on follicle cells
- Treat with T4
276
What is the normal level of free calcium in the body and where is it stored?
- 1-1.3mM
| - Skeleton
277
How much calcium is needed to be taken in daily to maintain levels?
- 500-1500mg
278
Where is calcium taken up and secreted?
- Taken up: Duodenum and jejunum
| - Secreted: Gut rich in calcium
279
What is bone's priority?
- Maintaining serum calcium levels
280
Where in the bone is calcium found?
- In collagen fibrils as calcium phosphate crystals
281
Outline briefly bone metabolism.
- Bone deposition: osteoblasts, produce collagen matrix, mineralised (by hydroxyopetite)
- Bone reabsorption: osteoclasts, acid breaks down bone.
282
What form of calcium can be reabsorbed?
- Free
283
What are the signs and symptoms of hypocalcaemia?
- Hyper-excitability of NMS
- Pins and needles
- Tetany (muscle spasms)
- Paralysis
- Convulsions
284
What are the signs and symptoms of chronic hypercalcaemia?
- Renal calculi (stones)
- Kidney damage
- Constipation
- Dehydration
- Tiredness
- Depression
285
How are calcium levels increased?
- Parathyroid hormone (PTH)
| - Vitamin D
286
How is PTH synthesis regulated?
- Low serum calcium up-regulates gene transcription.
- High serum calcium down-regulates
- T½ = 4mins
287
Why is PTH continually synthesised?
- There's little store of it.
- Chief cells degrade and synthesise PTH
- Cleavage of PTH in chief cells is accelerated by high serum calcium levels
- Released PTH is cleaved in the liver.
288
How is secretion of PTH regulated?
- Plasma conc of calcium decreases => increased PTH
| - Plasma conc of calcium increased => decreased PTH
289
What is the effect of PTH on bone?
- PTH induces osteoblastic cells to synthesise and secrete cytokines
- Cytokines protect osteoclasts from apoptosis
- PTH causes a decrease in osteoblasts
- Reabsorption of mineralised bone and release of Pi and Ca into ECF
290
What are the effects of PTH on the kidneys?
- Affects tubular cells in kidneys
- PTH increased calcium reabsorption in DCT reducing Ca excretion
- Pi is removed by kidney reabsorption inhibition
- Prevents calcium stone formation
291
What are the two forms of vitamin D and how are they formed?
- D3: made in skin and from dairy
- D2: from yeast and fungi added to margarine as supplement.
- Both form calcitriol by hydroxylation in liver and kidney
- T½: ¼ day
292
What effect does PTH have on the gut?
- Stimulates conversion of Vit D to its active form which increases the uptake of Ca from gut.
293
What effect does calcitriol have on the gut, bone and kidneys?
- Active uptake of Ca
- Transcellular transport
- Endocytosis and exocytosis of Ca
- Erodes bone
- Decreases urinary loss of Ca by stimulating reabsorption
294
What is the saying that signifies hypercalcaemia?
- Stones, moans (depression) and groans (abdominal pain)
295
What effect does hypercalcaemia have on PTH?
- Increased level of calcium leads to decreased levels of PTH
296
What are the effects of hypercalcaemia on the kidneys?
- Decreased calcitriol
- Less Ca taken from gut
- Ca absorption decreased
- Together= plasma Ca decreased
297
What are the treatments of hypercalcaemia?
- Fluids, as patients have lost excess fluid in urine
| - Removal of benign tumour in parathyroid glands
298
What happens if there's a deficiency of PTH?
- Abnormal Ca levels
| - Hypocalcaemia is life threatening
299
How is serum phosphate regulated?
- Vitamin D stimulates Ca and Pi uptake in gut.
