IMMS Flashcards
how much energy can be obtained from carbohydrates?
4kcal/gram
how much energy can be obtained from protein?
4kcal/gram
how much energy can be obtained from alcohol?
7kcal/gram
how much energy can be obtained from lipid?
9kcal/gram
what is the basal metabolic rate?
the amount of energy required to keep the body alive at rest
what is the energy required to maintain the basal metabolic rate?
1 kcal/kg body mass/hr
what factors can increase BMR?
1) high BMI
2) hyperthyroidism
3) fever/infection
4) pregnancy
5) exercise
what factors can decrease BMR?
1) ageing
2) being female
3) starvation
4) hypothyroidism
where does glycolysis take place?
cytosol
what is the overall equation for glycolysis?
glucose + 2ADP + 2Pi + 2NAD+ -> 2 pyruvate + 2ATP + 2NADH + 2H + + 2H2O
what happens to pyruvate under aerobic conditions?
pyruvate will enter the krebs cycle and undergo oxidative phosphorylation
what happens to pyruvate under anaerobic conditions?
pyruvate will convert to lactate and the lactate will undergo lactic acid fermentation
how many molecules of ATP is produced in aerobic respiration?
38
how many molecules of ATP is produced in anaerobic respiration?
2
what are the three ways that substrates can enter glycolysis?
- dietary glycose
- glycogenolysis
- other monosaccharides
what is dietary glucose?
glucose is directly absorbed into the bloodstream from the gastrointestinal tract and enters the pathway
what is glycogenolysis?
glucose is released from hepatic stores of glycogen and enters the pathway
what is hepatic?
relating to the liver
what are ‘other monosaccharides’ and how do they enter glycolysis?
galactose and fructose
enter glycolysis at various levels via common intermediates
where does galactose enter glycolysis?
in the first stage where it is converted to G6P
Why can glycogen in skeletal muscle only serve the individual muscle cells it is stored in?
glycogen in skeletal muscle cannot be fully broken down into glucose and therefore cannot leave the cell
why are glucose transporters required?
to allow glucose to pass from the extracellular space (bloodstream) to the intracellular space to be used by cells
what is Km?
the substrate concentration at which the reaction rate is 50% of the Vmax
what are the names of the four different types of glucose transporters?
- GLUT-1
- GLUT-2
- GLUT-4
what is a key feature of GLUT-1 and why is it important for its purpose?
has a low Km and therefore is active at low levels of glucose, which means it maintains the basal metabolic rate when glucose levels are low
where is GLUT-1 located?
all cells
what is a key feature of GLUT- 2 and why is it important for its purpose?
this means it can act as a glucose sensor and increases uptake in high glucose levels for storage. it also regulates the insulin release from pancreas
where is GLUT-2 found?
liver and pancreatic islet
what is a key feature of GLUT- 4 and why is it important for its purpose?
insulin dependant and therefore increases the uptake of glucose in the presence of insulin
what is the first reaction in glycolysis?
glucose is phosphorylated by hexokinase to form glucose-6-phosphate (G6P) using a molecule of ATP
what stages of glycolysis ca be inhibited and why?
stages1
why is glucose phosphorylated?
the phosphate introduces a negative charge which traps G6P in the cell as it cannot pass through the membrane
is stage
what is the first stage inhibted by?
product inhibition; higher concentrations of G6P inhibit hexokinase and slow the reaction
what is the name of the enzyme that inhibits stage 1 in the liver?
glucokinase
what is the second reaction of glycolysis?
G6P is converted into fructose-6-phosphate by glucose isomerase
where does fructose enter glycolysis?
during the second reaction of glycolysis (where fructose-6-phosphate is made)
what is the third step of glycolysis?
fructose-6-phosphate is phosphorylated by phosphofructokinase into fructose-1,6-bisphosphate using a molecule of ATP
how is the third step of glycolysis regulated?
- allosterically inhibited by ATP and activated by AMP
- phosphofructokinase is inhibited by glucagon, whilst insulin activates the enzyme
what is the forth step of glycolysis?
fructose-1,6-bisphosphate is converted into glyceraldehyde-3-phosphate (GA3P) and dihydroxyacetone phosphate (DHAP)s by fructose-bisphosphate aldolase
what is the fifth stage of glycolysis?
DHAP is converted into a second molecule of GA3P by triose phosphate isomerase
what is the sixth stage of glycolysis?
GA3P is converted into 1,3-bisphosphoglycerate (1,3-BPG) by glyceraldehyde phosphate dehydrogenase, producing a molecule of NADH
what is the seventh stage of glycolysis?
1,3-BPG is converted into 3-phosphoglycerate (3PG) by phosphoglycerate kinase, , generating a molecule of ATP
what is the eighth stage of glycolysis?
3PG is converted into 2PG by phosphoglycerate mutase
what is the ninth stage of glycolysis?
2PG is converted into phosphoenolpyruvate by enolase
what is the tenth stage of glycolysis?
phosphoenolpyruvate is converted into pyruvate by pyruvate kinase, yielding a second molecule of ATP
what happens during the Link Reaction?
pyruvate is then decarboxylated and dehydrogenated to form acetyl-coA by the pyruvate decarboxylase complexv
what is the first stage of the Krebs Cycle?
acetyl CoA (two-carbon molecule) joins with oxaloacetate (four-carbon molecule) to form citrate (six-carbon molecule) by citrate synthetase
what is the second stage of the Krebs Cycle?
citrate is converted to isocitrate (an isomer of citrate) by aconitase
what is the third stage of the Krebs Cycle?
isocitrate is oxidised to alpha-ketoglutarate (a five-carbon molecule) forming CO2 and NADH. the enzyme responsible is isocitrate dehydrogenase
what is the rate limiting step of the Krebs cycle?
the stage where alpha-ketogluterate is formed as isocitrate dehydrogenase can be allosterically inhibited (rate limiting step)
how can the Krebs cycle be regulated?
- metabolites: products of the cycle provide negative feedback on the enzymes that catalyse it eg. NADH inhibits the majority of the enzymes found in the cycle
- citrate: inhibits phosphofructokinase, a key enzyme in glycolysis. this reduces the rate of production of pyruvate and therefore of acetyl-CoA
- calcium: accelerates the TCA cycle by stimulating the link reaction
what is the fourth stage of the Krebs cycle?
alpha-ketoglutarate is oxidised to form a four-carbon molecule that binds to coenzyme A, forming succinyl CoA. this releases NADH and CO2. the enzyme involved is a-ketogluterate dehydrogenase
what is the fifth stage of the Krebs Cycle?
succinyl CoA is then converted to succinate (four-carbon molecule) and one GTP molecule is produced the enzyme involved is succinyl-coA synthetase
what is the sixth stage of the Krebs Cycle?
succinate is converted into fumarate (four-carbon molecule) and a molecule of FADH₂ is produced. the enzyme involved is succinic dehydrogenase
what is the seventh stage of the Krebs Cycle?
fumarate is converted to malate (another four-carbon molecule). the enzyme involved is fumerase
what is the eigth stage of the Krebs Cycle?
malate is then converted into oxaloacetate, producing another NADH. the enzyme involved is malate dehydrogenase
what is another usage of alpha-ketogluterate?
alpha-ketoglutarate can leave the cycle to be converted into amino acids
what is another usage of succinate?
succinate can be converted to haem
how many main complexes are located within the electron transport chain?
- I, II, III, IV, and V
what complex does NADH donate its electrons to?
I
what complex does FADH2 donate its electrons to?
II
what is complex V?
ATP synthetase
how are hydrogen ions pumped into the intermembrane space?
electrons being passed down complexes generates energy which is used to pump hydrogen ions into the intermembrane space. in doing so, a proton motive force is generated.
what happens when and after hydrogen ions are pumped into the intermembrane space?
an electrochemical gradient is generated which allows protons to re-enter the matrix via complex V (ATP synthetase)
how is ATP synthetised?
energy generated by hydrogen ions diffusing back into the matrix via complex V is harnessed, thereby creating ATP from ADP (oxidative phosphorylation)
how is the ETC naturally regulated?
1.when the concentration of ATP rises, there is less ADP for ATP synthase to use, which prevents large amounts of ATP being produced
2. when the concentration of ADP is high, there is a lot of ADP for ATP synthase to use and so more ATP is made
how and where is water formed in the ETC?
electrons combine with the hydrogen ions and oxygen to form water by complex IV
how can oxygen-free radicals accidentally form in the ETC?
electrons can leak out of the electron transport chain and can reduce oxygen, which can produce free radicals such as superoxide and hydrogen peroxide.
why does only glycolysis occur during anaerobic respiration?
without oxygen, the electron transport chain (ETC) cannot continue as there is no terminal electron acceptor. cessation of the ETC leads to reduced activity of the reactions before this step, such as the TCA cycle and glycolysis.
describe the process of anaerobic respiration
pyruvate is reduced to lactate (lactic acid) by NADH, yielding NAD+ by lactate dehydrogenase. NAD+ is recycled and glycolysis is able to continue as the supply of NAD+ has been replenished, yielding a net of 2 ATP molecules
why does anaerobic respiration happen faster than aerobic respiration?
less energy is produced for every molecule of glucose broken down (2ATP vs 32ATP), so more glucose must be broken down at a faster rate to meet energy demands
when may cells anaerobically respire?
during intense exercise, in ischaemic heart disease or when a malignant tumour outgrows its blood supply.
why is it important to remove lactate from the blood?
it is acidic and can cause muscle cramps
what are the ways in which lactate is removed from the blood?
- lactate is transported to metabolically active cells, such as in the heart and brain. it is converted back to pyruvate, which is then utilised in the Krebs cycle.
- lactate is transported to the liver and converted to pyruvate. pyruvate is then used in the process of gluconeogenesis to create more glucose
what is gluconeogenesis?
a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol and glucogenic amino acids
when does gluconeogenesis occur?
after around 8 hours of fasting when liver glycogen stores start to deplete and an alternative source of glucose is required
where does gluconeogenesis occur?
mainly in the liver and to a lesser extent in the cortex of the kidney
what are the precursors to gluconeogenesis?
- lacate
- glycerol
- amino acids
when does ketogenesis take place?
when there are carbohydrate shortages and increased beta oxidation has produces too much acetyl coA that has overwhelmed the Krebs cycle
when does fatty acid synthesis occur?
when there is an abundance of energy and acetyl coA builds up as high levels of ATP inhibits the Krebs cycle
where does fatty acid synthesis occur?
cytosol of the cell
describe the first stage of fatty acid synthesis?
oxaloacetate binds with acetyl coA to produce citrate, which can cross the mitochondrial membrane into the cytosol
what is the second stage of fatty acid synthesis?
citrate ligase converts citrate back into oxaloacetate, which then gets broken down into pyruvate and acetyl coA
what is the third stage of fatty acid synthesis?
pyruvate goes back into the mitochondria and is converted to oxaloacetate for Krebs
what is the final stage of fatty acid synthesis?
acetyl coA is converted into fatty acids
why and when does fatty acid metabolism occur?
in response to decreased blood glucose and high glucagon – mobilises fatty acids to target tissues
how many carbons do dietary fatty acids tend to have?
more than 14
what is the maximum number of carbons that cen be in fatty acids, which allows them to diffuse through the mitochondrial membrane?
12 (more than 12 cannot diffuse through and must be transported)
what is the carnitine shuttle?
the process by which acyl coA chains are converted and the reformed in order to cross the membrane
what is the process of the carnitine shuttle?
- acyl coA is converted to acylcarnitine by carnitine acyltransferase 1 (CAT1), which is found on the outer mitochondrial membrane.
- acylcarnitine is reformed to acyl coA by carnitine acyltransferase 2 (CAT2)
which is found on the interior side of the membrane - coA and carnitine are recycled
what is the purpose of beta oxidation?
to produce ATP, NADH and FADH2
describe the process of beta oxidation
the sequential removal of 2 carbon units by oxidation from acyl coA, where each round produces 1NADH, 1FADH2 and 1 acetyl coA
what happens to the products of fatty acid oxidation?
- FADH2 and NAD undergo oxidative phosphorylation
- acetyl coA re-enters the Krebs Cycle
why are ketone bodies used in preference to carbohydrates?
to help preserve glucose
describe the process of ketone synthesis
- two Acetyl-CoA’s are converted by thiolase to acetoacetyl CoA
- HMG-coA synthetase joins acetoacetyl coA with another acetyl coA to form 3-hydroxy-3-methyl-glutaryl-coA (HMG-CoA)
- HMG-CoA ligase breaks down HMG-CoA to acetoacetate
- acetoacetate degrades to acetone and can be converted by B-hydroxybutyrate dehydrogenase to -hydroxybutyrate
what is the rate limiting step of ketone body synthesis, and how is this regulated?
HMG-CoA synthase
increases with glucagon and decreases with insulin
how does diabetic ketoacidosis work?
a lack of insulin leads to glucose building up in the blood and not reaching cells. therefore, ketone levels are increased. as ketones are strong acids, it leads to ketone acidosis
what are some features and symptoms of diabetic ketone acidosis?
hyperventilation to remove acidic CO2
low pH, low pCO2, low CO3-, high pO2
where are sodium ions the most abundant?
within the extracellular fluid
what is the normal level of sodium ions in the plasma?
135-145 mmol/L (remember the odd numbers 135)
what is the normal intracellular sodium concentration?
10-12 mmol/L
why is maintaining the intracellular and extracellular sodium ion concentrations important?
- to maintain the resting membrane potential
- action potential propagation
- water travels in the direction of increasing sodium concentration by osmosis
what stimulates the renin-angiotensin-aldosterone system?
- reduced blood pressure
- reduced sodium concentration (as the blood has lower pressure and therefore there as more time for sodium re-absorption
where is renin released from?
granular cells of the juxtaglomerular apparatus
what does renin do?
renin converts angiotensinogen into angiotensin I, which is released from the from the liver
what converts angiotensin I to angiotensin II?
angiotensin converter ;enzyme
what does angiotensin II do?
- lead to arterial vasoconstriction to increase blood pressure
- increases the sensation of thirst
- stimulates an increase in the production of ADH
- stimulates the production of aldosterone
what does aldosterone do?
increases sodium reabsorption in ascending limb of LOH, which leads to water following, which increases blood pressure
what hormones remove excess sodium (and therefore reduce circulating blood volume)?
- atrial natriuretic peptide ANP
- brain natriuretic peptide BNP
how is ANP and BNP production stimulated?
raised blood volume and therefore pressure increases venous return and therefore stretches the atrial myocytes, which release ANP and BNP
how does ANP and BNP work?
- reduces aldosterone secretion from the adrenal glands
- reduces renin secretion from the juxtaglomerular apparatus
- dilating the afferent glomerular arteriole and constricting the efferent arteriole to increase blood pressure
therefore reducing the reabsorption of sodium ions from the DCT and the CD, helping to reduce blood pressure
how does anti-diuretic hormone work?
an increase in plasma osmolality is detected by osmoreceptors in the hypothalamus which stimulates the release of ADH from the posterior pituitary gland
this causes aquaporins to be inserted into the DCT and CD, increasing the reabsorption of water by osmosis
this leads to more concentrated urine
where is most of the sodium reabsorbed?
in the proximal convoluted tubule (~65%)
when and where is hypotension detected?
detected by baroreceptors in the carotid and aortic arch
what and where is hypovolaemia detected?
detected by reduced distension of atrial myocytes
what is hypovolaemia?
a decreased volume of circulating blood in the body
what do hypotension and hypovolaemia activate?
the sympathetic nervous system ; the increased reabsorption of sodium in the PCT, which increases fluid retention
what are the four pathways by which the sodium ion concentration can be regulated?
- renal sympathetic nerve activity
- renin-angiotensin-aldosterone system
- anti-diuretic hormone
- atrial natriuretic peptide and brain natriuretic peptide
what is hyponatraemia?
when the concentration of serum sodium decreases (<135 mmol/L)
what are some symptoms of hyponatremia?
- cerebral oedma (as water moves into the brain by osmosis)
- confusion
- headaches
- nausea
what is hypernatraemia?
when the sodium concentration in the serum increases (>145mmol/L)
what causes hypernatreaemia?
- dehydration
- increased water losses (eg. burns or diarrhea)
- kidney failure
what is the importance of maintaining K+ balance?
- maintain the resting potential of cells, as even as small change in the [K+] could lead to depolarisation/hyperpolarisation of cells
- important for maintaining cardiac function
what is the normal concentration of K+ in the ECF?
3.5-5 mmol/L (remmber 3-5 bananas)
what is the normal concentration of K+ in the ICF?
between 120-150 mmol/L intracellularly
where and what % is most of the K+ ions stored in?
98% of the body’s K+ is stored intracellularly
how are Na+/K+ movement controlled within cells?
Na+/K+ ATPase transmembrane pump which uses active transport to move 3 Na+ ions out of the cell (extracellularly) and 2 K+ ions into the cell (intracellularly)
what is produced in mitosis?
two daughter cells which are genetically identical to eachother and their parent cells
what is the first stage of mitosis?
prophase
what occurs during prophase?
- chromatin begins condensing into chromosomes
- mitotic spindles begin to form
- spindles attach to the centrosome
why does DNA need to condense into chromosomes?
to allow for easier separation in anaphase
what does a chromosomes look like?
two genetically identical chromatids, joined by a centromere
what are mitotic spindles made from?
microtubules
how many centrosomes are there within each cell?
2
what occurs during prometaphase?
- nuclear envelope begins to break down
- the spindle fibers attach to the centromere
what happens during metaphase?
- chromosomes alight at the metaphase plate (equator of the cell)
what happens during anaphase?
the spindle fibers contract, pulling the sister chromatids to the opposite poles of the cell
what happens during telophase?
- the nuclear envelope starts to reform
- chromosomes start to de-condense.
- spindle fibers break down
what happens during cytokinesis?
- the cytoplasm divides to form two new cells
- this happens by forming a cleavage furrow
what is produced during meiosis?
4 non-identical haploid daughter gametes
what happens during meiosis I?
homologous chromosomes are separated into two cells such that there is one chromosome (consisting of two chromatids) per chromosome pair in each daughter cell, i.e. two chromosomes total
what happens during prophase I?
- the nuclear envelope disintegrates
- chromosomes begin to condense
- spindle fibers appear
- crossing over occurs
what are the regions where crossing over occurs called?
chiasmata
what happens during prometaphase I?
spindle fibers attach to the chromosomes at the centromeres
what happens during metaphase I?
- homologous chromosomes align along the equator of the cell
- independent assortment occurs
what happens during anaphase I?
the homologous chromosomes are pulled towards the opposite poles of the cell as the spindle fibres contract
what happens during telophase I?
the nuclear envelope reforms and spindle fibres disappear
what happens during cytokinesis I?
the cytoplasm and cell divide resulting in two cells that are technically haploid
what happens during prophase II?
same as prophase I
what happens during prometaphase II?
same as prometaphase II
what happens during metaphase II?
chromosomes line up in single file along the equator of the cell
what happens in anaphase II?
sister chromatids are pulled to opposite poles of the equator
what happens in telophase II?
same as telophase I
what happens in cytokinesis II?
the cytoplasm and cell divide producing 2 non-identical haploid daughter cells
what is nondisjunction?
failed separation of chromosomes during anaphase, so either whole chromosomes (error occurring in meiosis I) or chromatids (error occurring in meiosis II) move to the same pole of the cell
what is monosomy?
having one copy of a chromosome, e.g. Turner syndrome (45, X)
what is trisomy?
having three copies of a chromosome, e.g. Edward’s syndrome (trisomy 18)
what is translocation?
an exchange of material between two chromosomes, resulting in an abnormal rearrangement
what is balanced translocation and its effect ?
no gain or loss of genetic material, usually harmless
what is imbalanced translocation and its effects?
the exchange of chromosomal material results in extra or missing genes in a daughter cell, it is known as unbalanced and can have clinical effects
what is the genetics of downs syndrome?
an extra copy of chromosome 21 (trisomy 21
what are the four phases of the cell cycle?
Gap 1 (G1), synthesis (S), Gap 2 (G2), and mitosis (M)
what is the G0 phase?
where cells undergo terminal differentiation, as they perform its function without actively preparing to divide (could be permanent, or could enter G1 again)
what phases compose of interphase?
G1, S, and G2
what happens during the G1 phase?
- cell increases in size
- cellular contents are duplicated
what happens during the S phase?
- DNA replication
- each of the 46 chromosomes (23 pairs) is replicated by the cell
what happens during the G2 phase?
- cell grows more
- organelles and proteins develop in preparation for cell division
what happens during the M phase?
- mitosis followed by cytokinesis (cell separation)
- formation of two identical daughter cells
what is the key checkpoint in the cell cycle called, and when does it happen?
restriction point (R)
occurs at G1
where are the other checkpoints for the cell cycle?
at the transitions between G1 and S, and G2 and M
what is the tumour suppressor gene and its role?
p53 is a tumour suppressor gene that stops the progression of the cell cycle and starts repair mechanisms for the damaged DNA, if damage is detected at any checkpoint
what happens if the DNA can not be repaired in a cell cycle?
the cell will undergo apoptosis and can no longer replicated
what are the three stages of DNA replication?
initiation, elongation and termination
what is DNA initiation?
- topoisomerase uncoils DNA. DNA helicase unwinds the double helix and exposes each of the two strands so that they can be used as a template for replication, by breaking the hydrogen bonds between complementary bases. single stranded bases attach to prevent re-annealing to other strands
- DNA primase synthesises a small RNA primer, which tells DNA polymerase where to start replicating
- DNA ligase joins together Ozaki fragments on the lagging strand
what is DNA elongation?
free DNA nucleotides are attached to the template strands by DNA polymerase and complementary base pairing
what direction does DNA polyermase add bases?
reads in 3’-5’ and synthesises in 5’-3’
why is the leading strand quicker than the lagging strand?
only needs to synthesise an RNA primer at the beginning, as the DNA polymerase moved in the same direction as the helicase
why does the lagging strand lag?
is read in the 5’ to 3’ direction, but DNA polymerase cannot add bases to the 5’ end, therefore it keeps needing to add RNA primers to synthesise in fragments (Okazaki fragments)
what is DNA termination?
no more DNA template strand left to replicate (i.e. at the end of the chromosome) or two replication forks meet DNA replication stops
what does DNA ligase do?
join together Okazaki fragments to create a complete strand
what type of genetic condition is sickle cell anaemia?
an autosomal recessive condition
what causes sickle cell anaemia?
an adenine base is swapped for a thymine base in one of the genes coding for haemoglobin; this results in glutamic acid being replaced by valine.
glutamic acid is hydrophilic, whereas valine is hydrophobic.
the hydrophobic region results in haemoglobin having an abnormal structure
what are the symptoms of sickle cell anaemia and what causes it?
blockages of capillaries, leading to ischaemia and potentially necrosis of tissues and organs. pains called ‘crises’
what are amino acids?
the basic building blocks of proteins
what is significant about the R group of amino acids?
gives the amino acid specific features according to its polarity and charge, which then affect the chemical and biological properties of the protein
how many amino acids are there?
21
how many essential amino acids are there any why are they considered essential?
9, as they must be consumed in the diet and can not be synthesised in the body
what is the primary structure of an amino acid?
the sequence and number of amino acids in a polypeptide chain
what type of bonds keep amino acids together?
peptide (covalent) bonds between the N and C terminal
what is the secondary structure?
further folding of the polypeptide chains to form alpha helices and beta pleated sheets
what type of folding is involved in protein secondary structure?
hydrogen bonds between the hydroxyl (OH) group and the hydrogen molecule of the adjacent amino acid
what is an alpha helix?
a coil formed by hydrogen bonds between the carbonyl group and the amino group of different amino acids
what is an beta pleated sheet?
ormed by hydrogen bonds between the carboxyl group of one amino acid on one sheet and the hydrogen molecule of an amino acid on another sheet
what is the tertiary protein structure?
further modification of the secondary structure to a 3D shape, which is usually globular caused by the interaction between the R groups of amino acids
what is protein denaturation?
disruption between the interaction of the R groups in the tertiary structure which leads to the protein losing its shape and function
what is the type of bonding involved in protein structure?
hydrogen bonds, ionic bonds, disulphide bridges and hydrophobic interactions
what is the quaternary protein structure?
multiple polypeptide chains bonded together formed by the interactions of R groups between different polypeptide chains
what are the two stages to protein synthesis?
- transcription
- translation
what are the three stages of transcrption
- initiation
- elongation
- termination
what occurs during initiation?
topoisomerase, helicase SSBs. RNA polymerase moves along DNA until it recognises a promoter sequence TATA, which shows the starting point of RNA transcription, and unwinds the DNA double helix
what are transcriptional factors?
proteins that control the rate of transcription; they too bind to the promoter sequences with RNA polymerase
what is DNA elongation in DNA replication?
the template strand is read in a 3’-5’ direction and provides a template for the new mRNA molecule, as RNA polyermase uses free RNA nucleotides to form the new strand by catalysing the formation of phosphodiester bonds between adjacent ribonucleotides by complementary base pairing
why are coding strands called as such?
its base sequence is identical to the synthesised mRNA, except for the replacement of thiamine bases with uracil
what is the termination stage of protein synthesis?
RNA polymerase synthesises RNA until a stop sequence is reached
what is splicing?
the removal of introns from pre-mRNA and the joining together of exons by ligation
what are the three stages to protein translation?
- initiation
- elongation
- termination
what happens during the initiation phase of protein translation?
- start codon AUG is recognised
- the 5’ end of the mRNA attaches to the small unit of the ribosome
what happens during the elongation phase of protein translation?
tRNA (that carries amino acids) with a complementary anticodon to the codon on the mRNA arrives at the ribosome. condensation reactions occur with adjacent amino acids
what happens during termination of protein translation?
a stop codon is read, and the polypeptide is released into the cytoplasm
what are the three main types of cell surface receptors?
- ion channel receptors
2.G protein-coupled receptors - enzyme-linked receptors
what are ion channel receptors with examples?
gates that open to provide ions with entry into the cell e.g. voltage-gated ion channels and ligand-gated ion channels
what are g-protein coupled receptors?
use g-proteins to participate in cell signalling
what are enzyme linked receptors?
have a catalytic site on their surface associated with an enzyme or has enzymatic properties itself
what are endo and exo cytosis?
bulk, active transport of products across the cell membrane
what is endocytosis?
the process by which substances are engulfed into the cell
what is exocytosis?
the process by which substances are released from the cell
what are the three main types of endocytosis?
- phagocytosis
- pinocytosis
- receptor-mediated endocytosis
what is phagocytosis?
engulfing large, solid particles such as bacteria into the cell for immune purposes. the cell membrane invaginated around the particle too create a vacuole within the cell
what is pinocytosis?
the non-specific uptake of fluid surrounding the cell, allowing it to take in nutrients such as ions, enzymes and hormones, caused by cell membrane invagination
what is receptor mediated endocytosis?
uptake of specific target substances, such as iron, via their receptor. receptors cluster in regions, and when the target substance meets the receptor, the receptors invaginate bringing the substance into the cell
what is exocytosis?
the process by which large molecules are moved out of the cell
describe the process of exocytosis?
vesicles are packaged within the cell and transported to the cell membrane, where their phospholipid bilayers fuse allowing the contents to be released out of the celln
what are the two forms of chromatin?
- euchromatin = loose coils and is expressed
- heterochromatin = tight coiled, not expressed
what happens in the nucleolus?
ribosomal RNA synthesis
what happens at the smooth endoplasmic reticulum?
membrane lipid synthesis, protein storage and phase 1 detoxification
what happens at the rough endoplasmic reticulum?
protein synthesis
what happens at the different parts of the Golgi apparatus?
- cis- receives protein/lipid
vesicle - medial- adds sugars to these
- trans packages modified molecules into vesicles for exocytosis
what is the perinuclear hof?
the Golgi of plasma cells that are distinguished compared to other cells
what are lysosomes, how is their pH maintained and why is this important?
degrades proteins + cell autolysis
pH of 5 maintained by H+/K+ ATPases, which prevents the outside of the cell from becoming acidic and therefore denaturing other ells
what are peroxisomes? what are their functions?
small membrane bound organelles that carry out beta oxidation of fatty acids. they generate hydrogen peroxide, which produces a OH free radical. removes H from lipids, alcohols and toxic substances
what are the three main types of filaments within the cytoskeleton?
microtubules, microfilaments and intermediate filaments
what are microtubules, their diameter and function?
tubulin motor proteins that are composed of an alpha and a beta structure (dimer). diameter of 25nm with a function in mitosis and a component of cilia
what are intermediate filaments, their diameter and function?
no motor protein, 10nm diameter with a function in cell integrity and cell to cell contact
what are microfilaments, their diameter and function?
myosin motor proteins which maintain cell shape and motility. 5-7nm
what is lipofuscin?
a yellow-brown pigment granules composed of lipids and lysosomal/peroxisomal oxidative digestion residue. considered to be a ‘wear and tear’ pigment
where are lipids stored in the body?
in adipocytes, as white stainingds
what are glycoproteins?
glucose reserve in skeletal muscles and the liver
what are the two main types of membrane proteins?
receptors and channels
what are membrane receptors with examples?
outside binding sites that trigger intracellular responses e.g. ion channels and G-coupled proteins
what are membrane channels with examples?
allow substances in and out of the cell, e.g. voltage gates. ligand gated and mechanical gates
what are mechanical gates channels?
opens when stretched
what are G-coupled receptors?
extracellular binding sites that activate a chain pathways internally, leading to a cascade of internal reactions.
what are the four types of cell junctions?
tight junctions, gap junctions, desmosomes, adherents
what are tight junctions and where are they found ?
allow no passage of substances, with the cells in a sheet e.g. GI tract and blood brain barrier
what are adherents ?
junctions formed from actin which forms bundles of cells
what are desmosomes?
joins cells together by intermediate filaments
what are gap junctions, where are they found?
allows the passage of ions through adjacent cells, key in myocardium contraction (contracts as a synctum)
what are the three methods of homeostasis?
autocrine, paracrine and endocrine
what is autocrine?
acts on the same cell, with secretions into the ECF then acting again on the same cell
what is paracrine?
secretion into the ECF to act in a neghbouring cell
what is endocrine?
secretion into the blood, acts on a distant target cell e.g. ADH
what are peptide hormones with examples?
made from several amino acids, water soluble travels directly into the blood. binds to CSM surface, fast acting premade and stored e.g. ADH and insulin
what are amino acid hormones with examples?
derived from one amino acid, such as adrenalin. same properties as peptide hormones
what are steroid hormones with examples?
made from cholesterol, lipid soluble therefore transported on proteins in the blood. diffuses through the CSM, slow acting and not premade (made and transported) e.g. oestrogen and testosterone
what are the water distributions within the body?
in a 70kg, 60% is water so 42L. 28L is in the ICF and 14L is in the ECF. 11L is in the IF and 3L is in the plasma
what is a sensible loss of water?
measurable, e.g. pee and vomit
what is an insensible loss of water?
unmeasurable, e.g. sweat and breath
where is ADH produced?
posterior pituitary
where is aldosterone produced?
suprarenal cortex
what is osmolarity?
conc. solute per litre of solution
what is osmolality?
conc. solute per kg of solution
what is osmotic pressure?
pressure exerted by pure solvent on an solution needed to prevent inward osmosis
what is oncotic pressure?
albumin pressure in capillary wall keeping fluid in
what is hydrostatic pressure?
fluid pressure leading to water wanting to move out of capillary
what are symptoms of hypernatremia?
oedma and high blood pressure
what causes hyponatremia?
excess water, lowered aldosterone
what are symptoms of hyponatraemia?
lowered blood pressure, overhydrated intracellularly
what causes hyperkalaemia?
kidney failure, alkalosis and lowered aldosterone
what are symptoms of hypokalaemia?
nerve and muscle issues, as it is involved in regulation of resting membrane potential
what is causes hypokalaemia?
diarrhoea, acidosis, increased aldosterone
what are symptoms of hypokalaemia?
weakness and heart problems
what causes hypercalcemia?
increased parathyroid hormone, increased vitamin D, skeletal metastasis
what are symptoms of hypercalcemia?
bone and muscle weakness, calcification
what causes hypocalcemia?
decreased levels of parathyroid hormone, decreased vitamin D, GI malabsorption
what are symptoms of hypocalcemia?
muscle spasms, since needed for action potentials
what is a nucleoside?
pentose sugar and base (no phosphate)
what are uses of lipids?
energy, protection, lubrication and waterproofing
what are purines?
two rings (A+G)
what are pyrimidines?
three rings (C,T,U)
are co-enzymes proteins?
no, bind to enzymes to aid function
what is haemoglobin called in muscles and how is it different?
myoglobin, greater affinity for oxygen
what is the structure of haemoglobin?
quaternary, two alpha and two beta subunits
what is the structure of foetal haemoglobin?
two alpha and two gamma chains (increased affinity for oxygen)
what is the structure of sickled haemoglobin?
two alpha and two mutated gamma chains
what is the symbol for normal, foetal and sickled haemoglobin?
HbA, HbF and HbS
what type of disease is sickle cell, what causes the mutation, why does it cause symptoms and why is it beneficial?
autosomal recessive disease on the B chain on 11p, GAG becomes GTG, which means
valine is made instead of glutamic acid. RBCs have a lowered surface area due to sickled shape, RBCs are less flexible and more prone to damage. protects against malaria
when does spermatogenesis start?
begins at puberty
describe the process of spermatogensis
spermatogonia -> primary spermatocyte -> (M1) secondary spermatocyte -> (M2) spermatid -> maturation into spermatozoa
when does oogenesis start?
at birth, suspended until ovulation starts
describe the process of oogenesis?
oogonia -> primary oocyte -> M1 secondary oocyte +polar body -> M2 ootd +polar body -> ovum
what is non disjunction?
failure of chromosomes to separate in M1 or sister chromatids in M2
examples of genetic disorders caused by non disjunction?
trisomy: downs syndrome
monosomy: turners
what is gonadal mosaicaism?
healthy parent having mutated germline. diseases have increased chances of occurring with age eg Duchenne’s muscular dystrophy
what is polymorphism?
non pathogenic variations at a locus from a ‘wild type’ normal allele
what is consanguity?
2 relatives union
what is penetrance?
% people with expected phenotype from their genotype
what is variable expression?
same genotype differently expressed
what is anticipation?
where symptoms appear earlier and more severe through generations e.g. Huntington’s
what is late onset?
manifestation after birth later in life (vs at birth; congenital)
what is autozygosity?
same mutation from both sides of the family
what is hemizygous?
genes carried as an unpaired chromosome e.g. men hemizygous for genes on Y
what is lyonisation?
1 female X (of the 2) randomly inactivated prevents 2x genes expressed as men
what is imprinting?
1 allele supressed of the 2 inherited
what is sex limited genes?
genes affect 1 sex only e.g. brca-1
what is dominant negative?
a product of a family allele affects the healthy allele’s function
what is allelic heterogeneity?
different mutations in some genes can cause some conditions
what is Knudson?
2 faulty genes need to cause cancer
what are autosomal dominant diseases?
appears heterozygous, affects generation to generation and males and females equally e.g. Huntington’s
what are autosomal recessive diseases?
appears homozygous, skips generations, affects males and females equally e.g. cystic fibrosis
what are x-linked diseases?
female carriers, affects men more (Duchenne)
what are Y-linked diseases?
only males, dad gives to all sons
what is the cystic fibrosis carrier frequency, incidence and what is the defect?
carrier freq 1/25, incidence 1/2500, most common auto rec. affecting white ppl in the UK. F508 defect
how to work out allelic frequency?
p2 + 2pq + q2 =1, p+q =1
what is a mitochondrial disease?
only maternal DNA, transmission from mother ot children
how is a male shown on a pedigree chart?
square
how is a female shown on a pedigree chart?
circle
how is a affected person shown on a pedigree chart?
coloured in
how is a dead person shown on a pedigree chart?
dash through
how is a unborn persons shown on a pedigree chart?
diamond
how is a terminated pregnancy shown on a pedigree chart?
triangle with a dash through
how is a consanguinity shown on a pedigree chart?
two lines between the couple
how is are identical twins shown on a pedigree chart?
branch out from the same point, with a line connecting branches
how is a twins shown on a pedigree chart?
branch out from the same point
how is a pregnancy not carried to term shown on a pedigree chart?
triangle
what is duplication and the different types?
repeating bases, tandem (adjacent), reverse tandem (adjacent and reversed), non-tandem (at another locus)
what is base deletion?
removes bases leading to a frame shift
what is inversion and the different types?
DNA segment reversed, paracentric (outside centromere), pericentric (includes centromere)
what is translocation?
exchange with non homologous chromosomes, equal or non equal
what is base substitution?
missense = change causes a new amino acid coded for
nonsense = change causes a premature stop codon formation
what are polymorphisms?
the presence of two or more variant forms of a specific DNA sequence that can occur among different individuals or populations
what are the different types of mutations?
polymorphisms, gene pathogenic, whole chromosomes
what is a karyotype?
shows numerical chromosome configuration
what is an ideogram?
shows distinct banding of chromosomes
what causes turners syndrome?
X monosomy
what causes Down’s syndrome?
trisomy 21
what causes Edwards syndrome?
trisomy 18
what causes Patau’s syndrome?
trisomy 13
what causes Kleinfelder’s syndrome?
XXY trisomy
what is p on a chromosome?
short arm
what is q on a chromosome?
long arm
what is metabolism?
all intracellular reactions takes place in body (rate of this is metabolic rate)
how much calories from carbohydrates?
4kcal/g
how much calories from protein?
4kcal/g
how much calories from alcohol?
7kcal/g
how much calories from fat?
9kcal/g
how many g of alcohol in 1 unit?
8
how and where is fat stored in the body?
adipocytes ito cells as triglycerides
how and where is carbohydrate stored in the body?
liver skeletal muscles as glycogen
how and where is fat stored in the protein?
muscle and liver
what hormonal changes when the body wants to store macromolecules for the post-absorptive state?
increase in insulin, decrease glucagon
what hormonal changes when the body wants to use macromolecules?
insulin decreases, glucagon decreases
what is glyogenolysis?
glucose reserves get used up
what happens when glucose gets depleted?
protein stores are attacked, then fat stores
what regulates glycolysis?
1) hexokinase actively controlled by G6P
2) PFK allosterically effected by AMP (increased AMP=increased PFK action). inhibited by ATP
what is the rate determining step of glycolysis?
the conversion of fructose-6-phsophate to fructose 1,6 bisphosphate due to PFK1 enzyme
what steps of glycolysis produce ATP?
1,3 bisphosphoglycerate to 3 phosphoglycerate and phosphoenolpyruvate to pyruvate
how to remember glycolysis?
gross guys feed fat dorky girls balls 4P
how is the Krebs cycle regulated/
citrate synthase allosterically by ATP and NADH, competitively by succinyl CoA
isocitrate dehydrogenase (main) by higher ox phos demand, makes it go faster
a-ketoglutarate dehydrogenase by succinyl CoA and NADH
why is ammonia toxic to the krebs cycle?
crosses blood brain barrier, reacts w a-ketoglutarate and depletes oxaloacetate, halts TCA
boxidation
pls make notes
FA (uses ATP) -> acyl adenylate -> (using CoA and acyl CoA synthetase) acyl CoA. this all occurs in cytoplasm. caritine shuttles into mitochondrial matrix if less than 12C f.a chain. enters krebs within mitochondroal peroxisomes, leaves as acetyl CoA, excess goes t ketogensis but most goes to krebs
how much of the bodies ATP is made from B oxidation?
60%
under what conditions does ketogenesis occur?
when there is excess acetyl CoA in the body (not all can be used in the TCA)
describe ketogenesis
acetyl CoA converted to acetate, acetoacetate, B-hydroxybutyrate
what are ketones and how are they used for energy?
inactive, storage-like scenarios, when the need arises they are reverted back to acetyl-CoA for the TCA
what is diabetic ketoacidosis?
when the conc of ketones in the blood increases, blood glucose levels are decreases and acidity increases as ketones are weak acids. this affects haemoglobin
why can the liver not use ketones for fuel?
does not have enzymes that ketone -> acetyl CoA
can the brain use ketones?
mainly uses glucose but can use ketones
what is the pH of the blood?
7.35-7.45
how does buffers work within the blood?
CO2 + H2O -> H2CO3 ->(carbonic anhydrase) H+ HCO3-
how is excess CO2 removed?
excreted/ exits in ventilation
how is excess H+ removed?
renally excreted
how is excess HCO3- removed?
renally recycled
how to calculate pH?
pH = pKa + log10 [(A-)/ (HA)]
pH = 6.1 + log10 [(HCO3-)/(0.03 CO2)]
what are functions of haemoglobin?
- O2 transport (Hb + O2 -> HbO2)
- CO2 transport to lungs (carbaminohaemoglobin)
- Hb+CO2 -> HbCO2
buffer by mopping up excess H+, Hb + H+ -> HbH - NO transport around body for ventilation
what is acidosis?
blood pH<7.35
what is alkalosis?
blood pH>7.45
how does the body cope with pH changes?
renal and or metabolic responses compensate
how does the body cope with metabolic acidosis?
deep hyperventilation to reduce the levels of CO2
how does the body cope with metabolic alkalosis?
hypoventilation and renal HCO3- excretion to increase CO2 levels
how does the body cope with respiratory acidosis?
pH is low and CO2 levels are high, so the body increases renal HCO3- retention, which decreases O2 level (hypoxia)
how does the body cope with metabolic alkhalosis?
the pH is raised and CO2 is decreased, so renal excretion of HCO3- increases. oxygen levels decrease (hypoxia)
what is the anion gap?
what is the equation for the anion gap?
((Na+) + (K+) - ((Cl-) + (HCO3-))
what is the use of the anion gap and what is its normal range?
10-16 normally, used to identify potential acidosis clinically
what is the significance oh H2O2 in reactive oxygen species?
is not a radical but can be decomposed in chains of reactions like Fenton/Haber Weiss
what is the Fenton reaction?
Fe2+ + H2O2 -> Fe3+ + OH (rad) + OH-
what is the Haber Weiss reaction?
OH (rad)+ H2O2 -> O2- (rad) + H2O + H+
what do reactive oxygen species do?
acts both as a bactericide, damaging the bacterial DNA, RNA and proteins, as well as a signalling molecule that induces repair mechanisms of the epithelium as well as respiratory burst
what do high levels of ROS correspond with?
Parkinson’s, renal failure, diabetes
what is respiratory burst?
phagocytes engulf pathogens, oxygen is taken in and rapidly converted into ROS (namely OH rad and ClO-) by the oxidation of NAD. ROS act on bacteria destroying them
