MEH Flashcards
What is the definition of metabolism?
The process is which food is broken down into energy and raw materials to be used for repair, growth and activity of the tissues to sustain life.
What is a catabolic pathway?
Breaking down larger molecules into smaller ones, releasing energy.
It is an oxidative process, releasing hydrogen atoms, generating reducing power.
What is an anabolic pathway?
The synthesis of larger molecules from smaller molecules, requiring energy.
It is a reductive process, using hydrogen atoms.
What are exergonic and endergonic reactions?
Exergonic - releases energy.
Endergonic - requires energy.
What are the characteristics of exergonic reactions?
They can occur spontaneously.
They are -DeltaG.
They release chemical bond energy.
They are seen in catabolic reactions.
What type of reactions releases chemical bond energy, and what are some characteristics?
Oxidation - the removal of electrons or hydrogen atoms.
They are accompanied by reduction reactions - the gain of electrons or hydrogen atoms.
What are the 3 types of hydrogen carrier molecules, in their oxidised form?
NAD+.
NADP+.
FAD.
What are H-carrier molecules synthesised from, how are they converted between oxidised and reduced form, and what are they used for?
They are synthesised from vitamins.
They are converted between the two states through the loss or gain of 2 hydrogen atoms.
They are used for biosynthesis or for ATP production.
How much energy is released from the breaking of the gamma-phosphate bond of an ATP molecule?
31kJ/mole.
How much ATP is within the human body, and how is this sufficient for energy demands?
250g.
It is not a store for energy: it is a way of constantly turning over energy - a carrier of energy.
What are some high-energy signals and what do they activate?
ATP, NADH, NADPH, FADH.
They activate anabolic pathways.
What are some low-energy signals, and what do they activate?
ADP, AMP, NAD+, NADP+, FAD.
They activate catabolic pathways.
What is the molecule used to store energy when rapidly required, and how is it synthesised?
Creatine phosphate.
Creatine and ATP are catalysed by creatine kinase to form creatine phosphate and ADP.
It can be used in the first few seconds of exercise, once the ATP stores are depleted.
What is creatine kinase a marker of?
It is a marker of muscle damage.
It used to be used to signify MI’s but now use troponins.
What is creatinine a marker of, and what do different levels mean?
Creatinine is a marker of kidney function.
It is a breakdown product of creatine and is proportional to muscle mass, produced at a constant rate.
Elevated levels signify kidney function reduction.
What is tyrosine synthesised from, within the body?
The amino acid phenylalanine.
What is cysteine synthesised from, in the body?
The amino acid methionine.
What is refeeding syndrome, and what is the key abnormality caused by it?
It is where a patient who is starved or inadequately nourished is fed energy rich foods, which leads to rapidly increased plasma glucose levels, resulting in glycogen, fat and protein synthesis.
These processes utilise phosphate, magnesium and potassium, resulting in electrolyte abnormalities.
The key abnormality is hypophosphataemia.
What are the risk factors or refeeding syndrome?
A BMI < 16.
Unintentional weight loss of greater than 15% within 3-6 months.
10 days or more without (or very little) nutritional intake.
How should someone at risk of refeeding syndrome be re-fed?
5-10 kcal/ kg/ day.
It should be gradually raised to the requirements within the week.
What are the 4 stages, and their features, of catabolism?
Stage 1 - breakdown of dietary macronutrients for absorption, occurring in the GI tract.
Stage 2 - glycolysis, breaking down the metabolic intermediates, producing reducing power and 2 molecules of ATP, in the cytosol.
Stage 3 - TCA cycle, producing reducing power and GTP, occurring in the mitochondria.
Stage 4 - oxidative phosphorylation, utilising the reducing power for ATP production, occurring in the mitochondria.
What is the minimum requirement of glucose per day?
180g:
- 40g/24 hours from the RBCs, neutrophils, innermost cells of the kidney medulla, and the lens of the eye.
- 140g/24 hours from the brain.
Which glycosidic bonds do pancreatic amylase and isomaltase break down?
Pancreatic amylase = alpha-1,4 bonds.
Isomaltase = alpha-1,6 bonds.
What are the 3 types of lactose intolerance?
Primary lactase deficiency = absence of lactase persistence allele.
Secondary lactase deficiency = caused by injury to the small intestine.
Congenital lactase deficiency = autosomal recessive defect in the lactase gene.
Where are the different GLUT transports found throughout the body?
GLUT 1 = blood-brain barrier and RBCs.
GLUT 2 = small intestine, pancreatic beta cells, kidney and liver.
GLUT 3 = neurons and placenta.
GLUT 4 = adipose and skeletal muscle.
GLUT 5 = spermatozoa and intestine.
They utilise passive transport, unlike SGLTs.
What are the functions of glycolysis?
2 NADH produced.
2 ATP produced.
Metabolic intermediates.
What are the 2 main rate-determining enzymes of glycolysis, and why are there so many enzymes?
Phosphofructokinase and hexokinase (glucokinase in the liver).
There are so many as:
- There is better control.
- Better versatility; can produce useful intermediates.
- Efficient energy conservation.
- Chemistry is easier.
What are some important intermediates of glycolysis?
2,3-bisphosphoglycerate - regulates affinity for oxygen of red blood cells.
Glycerol phosphate - important for triglyceride and phospholipid synthesis.
What allosteric regulators inhibit and stimulate phosphofructokinase?
Inhibitors:
- ATP.
- Citrate.
Stimulators:
- AMP/ ADP.
- Fructose-2,6-bisphosphate.
How is hexokinase (glucokinase in the liver) regulated?
Both (and phosphofructokinase) by insulin: glucagon ratio - insulin stimulates, glucagon inhibits.
ONLY hexokinase inhibited by the product of its reaction - glucose-6-phosphate.
When is lactate produced?
In pathological situations, such as in shock and congestive heart failure.
Naturally, without major exercise.
Increased with strenuous exercise.
What are the two enzymes involved in fructose metabolism, and what are their reactants and products?
Fructokinase - converts fructose into fructose-1-P.
Aldolase - converts fructose-1-P into glyceraldehyde-3-P.
What are the 3 enzymes involved in galactose metabolism, and what are the reactants and products?
Galactokinase - converts galactose into galactose-1-phosphate.
Uridyl transferase - converts galactose-1-phosphate into glucose-1-phosphate.
UPD-galactose epimerase - converts galactose-1-phosphate into UDP-galactose.
What organs does galactose-1-phosphate affect and what enzyme is in deficiency for it to accumulate with?
The brain, liver and kidneys.
Associated with galactose-1-phosphate uridyl transferase enzyme.
When would galactose be converted to galactitol, what is this done by, and what is the outcome?
It occurs when there is an accumulation of galactose, seen with a galactokinase or uridyl transferase deficiency.
It is converted by aldose reductase.
Accumulation in galactitol causes cataracts.
What is acetyl-CoA derived from?
Vitamins - particularly vitamin B’s.
What is pyruvate dehydrogenase formed from, and what is it sensitive to?
It is a multi-enzyme (5) complex.
It is sensitive to vitamin B1 deficiency.
What is the central pathway in catabolism of sugars, fatty acids, ketone bodies, amino acids and alcohol?
TCA cycle.
Where is the energy for ATP synthesis coming from?
The dissipation of energy from high-energy electrons, as they travel across the electron transport chain, supplied by the NADH and FADH2.
What are the 4 ‘layers’ of a mitochondrion?
The outer mitochondrial membrane.
The inter membrane space.
The inner mitochondrial membrane.
The mitochondrial matrix.
How many protons do each of the proton translocating complexes move, per 2 electrons?
PTC1 = 4 hydrogen ions.
PTC3 = 4 hydrogen ions.
PTC4 = 2 hydrogen ions.
What percentage of energy dissipated from the high energy electrons is used to move the hydrogen ions, and what happens to the rest of the energy?
30% of the energy is required to move the hydrogen ions across the mitochondrial membrane, with the rest being dissipated as heat.
What is the proton motive force?
An electrochemical gradient of positive charged hydrogen ions, generated across the inner mitochondrial membrane.
How is the proton motive force used to generate ATP?
H+ ions are impermeable to the inner mitochondrial membrane, and so they are transported down the electrochemical gradient through the ATP synthase.
The energy from movement of these protons drives the synthesis of ATP, from ADP.
What are some examples of electron transport inhibitors and oxidative phosphorylation uncouplers, what do they do?
Inhibitors = cyanide and carbon monoxide - prevents the movement of electrons through the ETC.
Uncouplers = fatty acids, dinitrophenol, dinitrocresol and UCP1 - dissipate the PMF as heat.
How does brown adipose tissue work to increase the temperature of new born infants?
In response to cold, noradrenaline is released which activates lipase to release fatty acids from TAGs.
These fatty acids undergo beta-oxidation, giving reducing power to FADH2 and NADH.
The fatty acids also activate UCP1, which is present in brown adipose.
UCP1 facilitates the movement of H+ ions back across the inner mitochondrial membrane, dissipating the PMF as heat.
What is the net yield of ATP from 1 glucose molecule?
32 moles.
What are the 3 lipid molecules used as fuel molecules?
Fatty acids.
Glycerol.
Ketone bodies.
What are the two products of beta-oxidation, and what occurs with them?
Shorter fatty acid chain - can enter beta-oxidation again or be stored as TAG.
Acetyl-CoA - enters the TCA cycle.
What are the characteristics of ketone bodies?
They are acidic.
They are soluble.
They can be used as an alternative fuel to glucose.
They can be used by peripheral tissues.
They are converted into acetyl-CoA when in excess.
Which ketone body is not a biological fuel?
Acetone.
How can acetyl-CoA be converted to ketone bodies, and what is the other final product from the intermediate (how does it get there)?
Acetyl-CoA is converted to HMG-CoA by HMG-CoA synthase.
HMG-CoA synthase is then converted to acetoacetate by HMG-CoA lyase (which can then be converted into acetate or beta-hydroxybutyrate).
Alternatively, HMG-CoA can be converted into cholesterol by HMG-CoA reductase.
How much energy does a gram of fat, alcohol, protein and carbohydrate have in it?
Fat = 37kJ/g.
Alcohol = 29kJ/g.
Protein = 17kJ/g.
Carbohydrate = 17kJ/g.
What is the recommended limit of alcohol consumption per week for men and women?
14 units per week, spread over at least 3 days.
It is the same for both men and women.
What is the damage done when a ROS reacts with a base or with a sugar?
With a base, mutation and mispairing can occur.
With a sugar, a strand break and mutation on repair may occur.
What are the 3 types of nitric oxide synthase (NOS) enzymes, and what are their functions?
iNOS - (inducible) used in the respiratory burst.
eNOS - endothelial signalling.
nNOS - neuronal signalling.
How does glutathione act as an antioxidant, and what is required for it to function?
The thiol group on the cysteine residue donates an electron, and combines with an adjacent GSH to form GSSG.
This reaction is catalysed by glutathione peroxidase, which requires selenium to work.
How is GSSG returned to glutathione?
Glutathione reductase utilises the H+ and e- from NADPH, to form two glutathione molecules.
How is paracetamol removed at therapeutic levels?
Conjugated to glucuronide or sulphate.
What is creatinine a breakdown product of?
Creatine and creatine phosphate in the muscle.
It is usually produced at a constant rate.
What 3 amino acids are conditionally required in children and in pregnant women?
Arginine, tyrosine and cysteine.
What is required for aminotransferases to function?
Pyridoxal phosphate, a derivative of vitamin B6.
What do ALT and AST do?
ALT = convert alanine and alpha-ketoglutarate into pyruvate and glutamate, respectively.
AST = convert aspartate and alpha-ketoglutarate into oxaloacetate and glutamate, respectively.
What enzymes can deaminate amino acids?
Amino acid oxidases.
Glutaminase.
Glutamate dehydrogenase.
Broadly speaking, what are all of the defects in the urea cycle?
They are all genetic disorders that cause a partial loss of enzyme function.
Complete loss of one of the 5 enzymes would be lethal.
What does the severity of urea cycle defects depend on?
The nature of the defective enzyme.
The amount of protein eaten.
Describe how glutamine transports the amino acid amine group for disposal.
- Ammonia is combines with glutamate to form glutamine.
- This reaction is catalysed by glutamine synthetase.
- Glutamine is cleaved by glutaminase to release the ammonia for the urea cycle in the liver or excretion via the kidney.
Describe how alanine transports the amino acid amine group for disposal.
Amine groups are transferred to glutamate by transamination.
Pyruvate is then transaminated by glutamate to form alanine.
Alanine is transported in the blood to the liver where pyruvate is formed again via transamination.
The amine group enters the urea cycle for disposal.
Pyruvate is converted to glucose via gluconeogenesis for use by the tissues.
What is the deficiency in phenylketonuria, and what is the treatment?
It is an autosomal recessive defect in the phenylalanine hydroxylase enzyme.
It is treated by have a low phenylalanine with enriched tyrosine diet, with no artificial sweeteners and a low protein diet.
What are the symptoms of phenylketonuria?
Musty urine smell - phenylketones building up in the urine.
Microcephaly.
Seizures.
Hypopigmentation.
Developmental delay.
Intellectual disability.
What is the defect in homocystinuria, and what is the treatment?
It is an autosomal recessive defect in the cystathionine beta-synthase
Treatment is a low methionine diet (avoid milk, fish, meat, cheese, etc.). Cysteine, vitamins B6 and B12, and folate supplements.
What glycosidic bonds are linked for the glycogen chains and branches, and what is the ratio of them?
Chains = alpha-1,4.
Branches = alpha-1,6.
A 1:10 ratio in favour of chains.
What is McArdles disease?
It is a defect in the glycogen phosphorylase enzyme, leading to an excess of glycogen in the muscle and liver.
What are the 3 key enzymes of gluconeogensis?
Main 2 are PEPCK and fructose-1,6-bisphosphate.
The other is glucose-6-phosphatase.
How are TAGs stored?
In anhydrous form in adipocytes.
They are a high energy store.
Adipocytes can increase in size by about 4 fold before increase in total number of cells (of which is irreversible).
Outline the steps of fatty acid synthesis (lipogenesis).
In the liver, glucose is converted to pyruvate via glycolysis.
Pyruvate is converted to acetyl-CoA in the mitochondria (pyruvate dehydrogenase) and enters the cytoplasm.
Acetyl-CoA is converted to malonyl-CoA via acetyl-coA carboxylase.
Malonlyl-CoA is added to fatty acids by fatty acid synthase complex (adding C2).
What molecules are required for lipogenesis to occur?
ATP and NADPH.
How do glucagon/ adrenaline and insulin assert their effects on hormone sensitive lipase?
Glucagon/ adrenaline phosphorylates hormone sensitive lipase, activating it.
Insulin dephosphorylates hormone sensitive lipase, inhibiting it.
How do glucagon/ adrenaline and AMP, and insulin and citrate assert their effects on acetyl-CoA carboxylase?
Glucagon/ adrenaline phosphorylate the enzyme, and AMP binds allosterically, inhibiting it.
Insulin dephosphorylates the enzyme, and citrate binds allosterically, activating it.
What is the structure of a lipoprotein, and what can they carry?
It is a phospholipid mono layer with a small amount of cholesterol, in a micelle shape.
It has integral and peripheral apolipoproteins associated to it.
It can carry cholesterol esters, fat soluble vitamins and TAGs.
How do the lipoproteins differ from each other?
They contain different apolipoproteins, and different TAG, cholesterol and cholesterol ester contents.
What are the main apolipoproteins associated with HDL and the other lipoproteins?
HDL = apoAI.
VLDL, ILD and LDL = apoB.
What are the two different fates for TAGs released by VLDLs based on their location?
In muscle, the TAG is used for energy.
In the liver, the TAG is stored as fat.
What are the different percentages of TAG required for the conversion between VLDL, ILD and LDL?
VLDL depletes to 30% to become ILD.
IDL depletes to 10% to become LDL.
How can cells requiring additional cholesterol obtain cholesterol from HDL?
Using scavenger receptors.
How can HDL take cholesterol from peripheral tissues, and from VLDL?
The ABCA1 receptor from peripheral tissues.
Through the cholesterol-exchange transfer protein from VLDL.
What are hyperlipoproteinaemias caused by and what can there be defects in?
Caused by over-production or under-removal of lipoproteins.
Defects in enzymes, receptors or apolipoproteins.
Where do foam cells accumulate and what do they form?
They accumulate in the intima of the blood vessel wall, forming a fatty streak.
What do PCSK9 inhibitors do?
They inhibit the breakdown of LDL receptors in liver cells, meaning more LDL is removed from the plasma.
Where does haemopoiesis occur in foetus’, in infants and in adults?
In foetus’, it occurs in the yolk sac and then the spleen and liver.
In infants, it occurs throughout the skeletons bone marrow.
In adults, it occurs in the axial skeleton bone marrow.
What does haemopoiesis use and what are the 5 categories of lineage pathways?
It uses haemopoietic stem cells.
The 5 categories are:
- Thrombopoiesis.
- Granulopoiesis.
- Monocytopoiesis.
- Erythropoiesis.
- Lymphopoiesis.
What do erythropoietin and thrombopoietin regulate? Where are they secreted from?
EPO = stimulate formation of RBCs, secreted by the kidney.
Thrombopoietin = stimulates formation of platelets, secreted by the liver and some by the kidney.
What can happen to the haemopoietic stem cells in myeolfibrosis or thalassaemia?
They can migrate to the liver or spleen to undergo extramedullary haemopoiesis.
What do the red and white pulp do?
Red pulp = lined by macrophages to remove old and defective red blood cells.
White pulp = lined with white cells to remove encapsulated bacteria, mainly.
Where do you start palpating for splenomegaly?
The right iliac fossa.
What encapsulated bacteria are you at increased risk of sepsis with hyposplenism? What must be given to patients?
Neisseria meningitidis.
Haemophilus influenzae.
Streptococcus penumoniae.
They must be given lifelong antibiotic prophylaxis and vaccinations.
What are the characteristics of red blood cells?
They live for 120 days.
Biconcave shape.
Have no nucleus or mitochondria.
State some functions of red blood cells.
Deliver oxygen to tissues.
Carry haemoglobin, and maintain it in its ferrous state.
Maintain osmotic equilibrium.
Generate energy.
What are some features haemoglobin?
A tetramer of 2 pairs of alpha and beta chains, each with its own haem group.
Globin gene clusters are on chromosomes 11 and 16.
It binds to oxygen to carry out round by the body and undergoes a conformational change to increase the affinity of it.
There are different types of Hb with different combinations of globin chains.
What age do infants switch from foetal to adult haemoglobin?
3-6 months.
What are the 4 proteins involved in hereditary spherocytosis?
Spectrin - cross links the actin cytoskeleton to the plasma membrane.
Ankyrin - links integral membrane proteins (band 3) to the spectrin.
Band 3 - facilitates chloride-bicarbonate exchange. It also bind ankyrin and protein 4.2.
Protein 4.2 - ATP-binding protein that is associated with band 3 and ankyrin.
What is bilirubin conjugated with in the liver?
Glucuronic acid.
What is the maturation of neutrophils controlled by, and what are some other things that it does to neutrophils?
The hormone G-CSF.
It increases production and enhances chemotaxis and phagocytosis ability of neutrophils.
What are monocytes, what do they differentiate into and what causes proliferation of them?
They are the largest blood cell that circulates in the blood for 1-3 days, before entering tissues.
Here, they differentiate into macrophages or dendritic cells.
Bacterial infection, inflammatory conditions, myeloproliferative disorders and carcinomas cause proliferation of monocytes.
What is the life of an eosinophil and what do their granules contain?
They circulate in the blood for 3-8 hours before living in tissues for 8-12 days.
Their granules contain cytotoxic proteins such as elastase.
What are the 3 types of lymphocyte?
B-cells, T-cells and natural killer cells.
What is spectrophotometry and flow cytometry, and what are they used to measure?
Spectrophotometry = the amount of light absorbed, used to measure haemoglobin after cells have by lysed by a hypotonic solution.
Flow cytometry = impedance counting and different scatters to measure numbers and sizes of cells.
What is the PCV/ Hct?
The proportion of blood that is made up of RBCs.
What is the Hb value and what is its units?
It is the concentration of haemoglobin, given in g/L.
What is RDW used for?
To see when an iron deficient anaemia began developing.
If the anaemia is haemolytic.
How can erythropoiesis be reduced or dysfunctional?
Reduced - reduced EPO production from the kidney, due to anaemia of chronic disease (and less iron), kidney failure, etc.
Dysfunctional - the receptors that EPO binds to cannot stimulate production of RBCs, myelofibrosis so less haemopoietic stem cells, myelodysplastic syndromes.
What is an inherited cause of haemolytic anaemia, and how does it manifest?
Hereditary spherocytosis - mutations in genes coding for ankyrin, spectrum, protein 4.2 or band 3.
Leads to less flexible cells that are damaged more easily, and so are removed faster by the RES.
How does a G6PDH deficiency cause anaemia?
Less GSH able to be reformed and so the cells are more prone to oxidative damage:
- Lipid peroxidation leads to cell membrane damage.
- Aggregations of haemoglobin; Heinz bodies.
Red cells removed by the RES.
Outline some causes of excessive bleeding that may lead to anaemia.
Acute blood loss = childbirth, injury, surgery, ruptured blood vessel.
Chronic NSAID use = can cause GI bleeding as platelets less effective and effects on epithelium.
Chronic bleeding:
- Heavy menstrual periods.
- Kidney, bladder, or GI tumours.
- GI ulcers.
What happens in autoimmune haemolytic anaemias and what is the anatomical result on the body?
Autoantibodies bind to the red cells and they are destroyed by macrophages in the spleen.
This leads to splenomegaly.
What are some features of reticulocytes?
They are immature red blood cells - take around 2 days to mature.
They have no nucleus but still have some mitochondria.
They are larger than normal red blood cells.
Where is folate absorbed, stored, how long can the stores last and where is it converted to tetrahydrofolate?
Absorbed in the duodenum and jejunum.
Stored in the liver with stores lasting up to 3-4 months.
Converted to FH4 in intestinal cells.
When should folate be given and for what reason?
It should be given in folic acid form to women before pregnancy, for the first 12 weeks of pregnancy to prevent neural tube defects.
What are some folate deficiency-specific symptoms?
Reduced sense of taste.
Diarrhoea.
Paraesthesia in the hands and feet.
Muscle weakness.
Depression.
Anaemia related symptoms.
Outline vitamin B12 absorption and storage.
Binds to hepatocorrin in the stomach.
Travels to the intestine where it binds to intrinsic factor.
Intrinsic factor-B12 complex taken up into enterocytes by receptor-mediated endocytosis.
Binds to transcobalamin and transported round the body.
Stored in liver for 3-6 years.
What are the two types of autoantibody in pernicious anaemia?
Ones that block the binding of B12 to intrinsic factor.
Ones that prevent the B12-intrinsic factor complex from being taken up by receptor mediated endocytosis.
What are some haematological changes seen in cancer, related to red blood cells, neutrophils and platelets?
