IMMS Flashcards
Describe the features of the two types of chromatin
Tight coils of heterochromatin which are repressed
Loose coils of euchromatin which are expressed
Function of the nucleolus?
rRNA synthesis
Function of mitochondria
ATP synthesis
Function of SER
Membrane lipid synthesis
Protein storage
Phase 1 detoxification
Function of RER
Ribosomes on surface carry out protein synthesis
Function of the three parts of the Golgi
Cis - receives protein and lipid vesicles
Medial - adds sugar to these
Trans - packages modified molecules into vesicles to be exocytosed
What is a perinuclear hoff?
Visible circle of Golgi apparatus in plasma cells
Function of lysosomes
Contain hydrolysis enzymes that degrade proteins and carry out autolysis
What pH are lysosomes and how is this pH maintained?
5
H+/ K+ ATPases
Function of peroxisomes
Beta oxidation of of fatty acids
Produce and destroy hydrogen peroxide to form hydroxide ions
Removes hydrogen from lipid/ alcohol/ toxic substances
Microtubule diameter
25nm
Describe the structure of microtubules
Tubulin motor protein
Arranged as alpha and beta structure - a dimer
Function of microtubules
Mitosis
Component of cilia
Diameter of intermediate filaments
10nm
Do intermediate filaments have motor proteins?
No
Function of intermediate filaments
Cell integrity
Cell to cell contact
Diameter of microfilaments
5-7nm
Which motor protein is in microfilaments?
Myosin
Function of microfilaments
Cell shape and motility
Name some cell storage products
Lipofuscin, lipids, glycoproteins
What is lipofuscin, and how is it produced?
Wear and tear pigment
Oxidative lipid degradation
Produced in old cells
Colour of lipofuscin
Orangey brown
Staining of lipids
Pale/ white
What cells are lipids stored in, and in which other organ?
Adipocytes and in the liver
What are glycoproteins and where are they found?
Glucose reserves in skeletal muscle and the liver
Functions of cell membranes
Partially permeable
Boundary between the intracellular and extracellular space
Receptors for self
Link adjacent cells
How do cells act as receptors?
Outside binding triggers intracellular response
Describe G Coupled proteins
Extracellular binding activates transduction pathway internally
Cascade of internal reactions
Types of cell membrane channels
Ligand gated
Voltage gated
Mechanical gated (open when stretched)
Types of cell to cell junctions
Tight junctions
Adherens
Desmosomes
Gap junctions
Describe tight junctions
Prevent passage of substances between cells
Where are tight junctions found
GI tract
Blood brain barrier
Describe adherens
Adjacent actin
Bundles of cells joined
How do desmosomes work
Adjacent intermediate filaments joined
Describe gap junctions
Allow passage of ions between adjacent cells
In which organ are gap junctions important?
Heart
Myocardium - heart contracts as a synctium
What is
a) diffusion
b) osmosis
c) facilitated diffusion
a) movement of molecules down its concentration gradient
b) movement of water down its potential gradient across a partially permeable membrane
c) movement of molecules down a concentration gradient using a membrane protein
Describe active transport
Movement of molecules against a concentration gradient using energy
What is the difference between primary and secondary active transport?
Primary - e.g Na+/ K+ ATPase pumps - direct
Secondary - uses cotransport - indirect
What is exocytosis?
Vesicles bud off cell surface membrane and contents are released
What is endocytosis
Intake of molecules in phagosome vacuole
What is phagocytosis
Engulfing whole cells/ macromolecules by neutrophils/ macrophages
What is pinocytosis
Engulfing dissolved solutes
What is receptor mediated endocytosis
Engulfing ligand-receptor complexes
What is homeostasis
Maintenance of constant internal conditions within a normal range
What are the three modes of communication between cells
Autocrine
Paracrine
Endocrine
What is autocrine communication
Signalling molecule acts on the same cell
Secretion into ECF
What is paracrine communication
Signalling molecule acts on a nearby cell
Secretion into the ECF
What is endocrine communication
Signalling molecule acts on a distant target call by travelling in the blood
Give an example of a paracrine hormone
Ach at the nmj
Give an example of an endocrine hormone
ADH from posterior pituitary
What is negative feedback?
a highly regulated loop
what is positive feedback
not a loop
amplification e.g blood clotting
are peptide hormones water soluble
yes
do peptide hormones enter the cell or bind to the CSM
bind to the csm
are peptide hormones slow or fast acting
fast
are peptide hormones premade?
yes
what are steroid hormones made from?
cholesterol
are steroid hormones lipid or water soluble
lipid soluble
do steroid hormones enter the cell or bind to the CSM?
enter the cell by diffusing through the CSM
are steroid hormones slow or fast acting
slow
are steroid hormones premade?
no
give 2 examples of steroid and peptide hormones
oestrogen, testosterone
insulin, ADH
how much water is in the ICF?
28L
predominant electrolyte in the ICF?
K+
how much water is in the ECF
14L
how much water is in the interstitial fluid and plasma?
interstitial - 11L
plasma - 3L
predominant electrolyte in the ECF
Na+
what is sensible water loss?
can be measured easily
give an example of sensible water loss
urine, vomit
what is insensible water loss?
water loss that cannot be measured easily
give an example of insensible water loss
sweat, breath
what does RAAS stand for?
renin-angiotensin-aldosterone system
when is RAAS activated?
fall in blood pressure detected by baroreceptors in the afferent arteriole
fall in NaCl detected by macula densa of DCT
what enzyme is released to trigger RAAS
renin
where is renin released from
juxtaglomerular cells
what converts angiotensinogen to angiotensin I
renin
what converts angiotensin I to angiotensin II, and where is it produced
ACE, lungs
actions of angiotensin II
ADH release
- acts on aquaporin II on collecting ducts
- increases collecting duct permeability
- increased water retention
- increase in blood pressure as ECF increases
- made in hypothalamus and stored in the posterior pituitary gland
Aldosterone release
- from suprarenal cortex of adrenal gland
- increases Na+ reabsorption in ascending limb of LOH
- water follows Na+
- bp increases as ECF increases
Triggers the sympathetic nervous system
what are the roles of ANP
antagonist to aldosterone
decreases blood pressure
when is ANP released
when atria are stretched as a result of an increase in blood pressure
what does ANP stand for
atrial natriuetic peptide
what does excess water cause
oedema
what is osmolarity
number of solute particles per litre of solvent
what is osmolality
number of solute particles per kg of solvent
what is osmotic pressure
pressure exerted by a pure solvent on a solution needed to prevent inwards osmosis (solvent to solution)
oncotic pressure
pressure exerted by plasma proteins, notably albumin, on a capillary wall keeping fluid in
hydrostatic pressure
pressure that pushes fluid out of a capillary
what is hypernatremia
abnormally high sodium concentration in the blood
causes of hypernatremia
dehydration, an increase in aldosterone, kidney failure
symptoms of hypernatremia
oedema, an increase in blood pressure
what is hyponatremia
abnormally low sodium concentration in the blood
what causes hyponatremia?
excess water, a fall in aldosterone
symptoms of hyponatremia
a fall in blood pressure, over hydrated intracellularly
what is hyperkalaemia
abnormally high potassium concentration in the blood
what causes hyperkalemia
kidney failure, a fall in aldosterone, alkalosis
what are the symptoms of hyperkalemia
nerve and muscle weakness - regulation of the resting membrane potential
what is hypokalaemia
abnormally low potassium concentrations in the blood
what causes hypokalaemia
diarrhoea, acidosis, an increase in aldosterone
what are the symptoms of hypokalaemia
weakness, heart problems
what is hypercalcaemia
abnormally high calcium concentration in the blood
what causes hypercalcemia
an increase in parathyroid hormone, too much vitamin D (which absorbs calcium), skeletal metastasis
what are the symptoms of hypercalcemia
bone and muscle weakness, calcification
what is hypocalcemia
abnormally low calcium concentrations in the blood
what are the causes of hypocalcemia
a decrease in parathyroid hormone, not enough vitamin D, GI malabsorption
symptoms of hypocalcemia
muscle spasms (needed for action potentials)
general formula for carbohydrates
(CH2O)n
what are the divisions of carbohydrates
mono, di, oligo and polysaccharides
what is the range of the number of carbons an oligosaccharide can have?
3-10
what bonds join monosaccharides to form polysaccharides?
glycosidic
what bonds are found in lipids
ester
how are lipids oxidised
fatty acid beta oxidation
what does amphipathic mean?
having both hydrophilic and hydrophobic parts e.g phospholipids
lipid functions
protection from mechanical damage, lubrication, waterproofing, energy source
how much energy do lipids contain per gram
9kcal/g
what are the components of nucleotides?
phosphate, pentose sugar, organic nitrogenous base
what are the bonds between the bases of nucleotides
hydrogen bonds
what are the bonds between the phosphate and sugar in nucleotides
phosphodiester
which nucleotides are purines?
adenine and guanine
how many rings do purines have?
2
which nucleotides are pyrimidines
cytosine, thymine, uracil
how many rings do pyrimidines have?
3
how many hydrogen bonds are between A and T, and C and G
2, and 3
what is a nucleoside
pentose sugar and base (no phosphate)
how many essential amino acids are there?
8
what is the configuration of a peptide bond?
CONH
what affects the properties of an amino acid?
R group
what is the primary structure of a protein?
sequence of amino acid
what is the secondary structure of a protein?
twisting and folding of the polypeptide chain due to hydrogen bonds
forms alpha helices and beta pleated sheets
what is the tertiary structure of a protein?
3D folding due to ionic bonds, hydrophobic interactions and disulphide bridges
what is the quaternary structure of a protein?
more than one polypeptide chain
how do enzymes work?
alternative pathway for a reaction to occur, with a lower activation energy
what are coenzymes
organic molecule (non protein) that binds to proteins to aid function
does myoglobin have a higher of lower oxygen affinity than haemoglobin
higher
structure of haemoglobin (HbA)
2 alpha chains, 2 beta chains
structure of foetal haemoglobin
a alpha chains, two gamma chains
name of sickle haemoglobin
HbS
structure of HbS
2 alpha, 2 mutated beta
genetics of HbS
autosomal recessive
mutated beta chain on 11p (short arm)
GAG TO GTG (substitution)
glutamic acid to valine
how does HbS cause symptoms?
RBC SA decreases due to sickle shape
less flexible and more prone to damage
why is sickle cell more common in Africa
protects against malaria
function of DNA
stores genetic information
what is the term for three DNA bases vs 3 RNA bases?
DNA - triplet
RNA - codon
function of RNA
transfers genetic information
which base is substituted in RNA?
T substituted for U
which enzyme unwinds the supercoil?
topoisomerase
which enzyme breaks hydrogen bonds between the bases to separate the strands?
helicase
what are the three stages of DNA replication?
initiation, elongation and termination
what are SSBs
single stranded binding proteins
coat the single DNA strands to prevent reannealing or snapping back together
what direction does DNA polymerase read in?
3’ to 5’
what direction does DNA polymerase synthesise in?
5’ to 3’
what does DNA polymerase do?
forms phosphodiester bonds between free nucleotides to extend the strand
function of DNA ligase
joins Okazaki fragments on the lagging strand by phosphodiester bonds
where does transcription occur?
nucleus
stages of transcription
preparation, production, termination, modification (splicing)
what is transcription
synthesis of mRNA from DNA
describe the preparation stage of transcription
topoisomerase unwinds the double helix by relieving the supercoils
DNA helicase separates the DNA apart by exposing the nucleotides
SSBs coat the single DNA strands to prevent reannealing
which promoter sequence is the recognition signal for starting
TATA
what is the start codon, and what does it code for
AUG
methionine
in what direction does the coding strand run in?
5’ to 3’
in what direction does the template strand run in?
3’ to 5’
describe the production stage of transcription
TATA sequence is the recognition signal for starting
AUG is the start codon - codes for methionine
free mRNA nucleotides line up next to their complementary bases on the template strand/ antisense strand of DNA
U-T, C-G
coding strand runs 5’ to 3’
template strand runs 3’ to 5’
ends at the stop codon - UAA/ UAG/ UGA
function of RNA polymerase
joins mRNA nucleotides
catalyses the formation of phosphodiester bonds
describe the modification stage of transcription
splicing
removal of introns
leaves axons - the coding part
how does mRNA leave the nucleus
nuclear pores
where does translation occur?
cytoplasm
which ribosome subunit does mRNA bind to?
small
which ribosome subunit does tRNA bind to?
large
what is the most common start codon?
AUG (methionine)
what is the product of transcription?
PRE mRNA
three bases on tRNA is called?
anticodon
function of tRNA
carries amino acid to mRNA
where does the polypeptide chain travel to after translation?
Golgi
how many autosomal and sex pairs of chromosomes do we have?
22 autosomal pairs
1 sex pair
where is DNA found in the cell?
nucleus and mitochondria (maternal)
name the two cell cycle checkpoints
G1 and G2 checkpoints (at the end of these stages)
name the stages of the cell cycle
interphase
-G1
-S
-G2
Mitosis
-PMAT
-cytokinesis
function of G2 checkpoint
checks DNA damage pre mitosis
damaged base excision by glycosylases
function of G1 checkpoint
checks DNA damage pre DNA replication
damage activates p53 tumour suppressor gene
p21 activated
autolysis
what occurs during G1?
organelles replicate
what occurs during S?
DNA replication
centrosome replication
what occurs during G2?
chromosomes condense
mitochondria and centrioles double
energy stores accumulate
what is G0?
normal function/ repair
some cells never leave this state e.g neurons
fully differentiated cells
what happens during prophase?
centrioles move to poles and form spindle
chromosomes condense
what happens during prometaphase?
centromeres bind to spindle via centromere
nuclear membrane breaks down
microtubules invade nuclear space
what happens during metaphase?
chromosomes line up on equator
what happens during anaphase?
sister chromatids separate and pulled to opposite poles of cell
V shape assumed
what happens during telophase?
nuclear envelope reforms
chromosomes decondense into chromatin
is cytokinesis part of mitosis?
yes, according to lectures even though some textbooks say no
what happens during cytokinesis?
cell cytoplasm divides into two daughter cells
difference between mitosis and meiosis
meiosis
- only in gametes
- recombination of genetic material for diversity
- two cell divisions
- 4 haploid daughter cells
what happens in meiosis 2?
separation of sister chromatids
what creates genetic variation in meiosis?
crossing over in prophase 1
independent segregation in metaphase 1
when does spermatogenesis begin?
puberty, and continue afterwards
is the cytoplasmic division in spermatogenesis even?
yes
describe the stages of spermatogenesis
spermatogonia, primary spermatocyte, 2 x secondary spermatocytes, 4 spermatids (immature sperm), which differentiate into mature sperm (spermatozoa)
what is the first meiotic division of spermatogenesis?
primary to secondary spermatocyte
what is the second meiotic division of spermatogenesis?
secondary spermatocyte to spermatid
when does oogenesis begin? then what happens?
birth
suspended until ovulation starts (periods)
is cytoplasmic division of oogenesis even or uneven?
uneven
how long does sperm produciton take?
60-65 days
how many sperm per ejaculate?
100-200 million
how many mitotic divisions to form oogonia?
30
when is meiosis 1 of oogenesis completed?
ovulation
when do oogonia enter prophase of meiosis 1 by?
8th month of intrauterine life
when is meiosis 2 of oogenesis complete?
fertilisation
describe the process of oogenesis
oogonia, primary oocyte, secondary oocyte (and polar body), ootid (and 2 more polar bodies), ovum
what is the first meiotic division of oogenesis?
primary oocyte to secondary oocyte
what is the second meiotic division of oogenesis?
secondary oocyte to ootid
what is a polar body?
byproduct of oocyte meiotic division
normally apoptoses
name the 2 meiotic pathologies
non disjunction
gonadal mosaicism
what is non disjunction?
failure of chromosomes to separate in m1
failure of chromatids to separate in m2
conditions caused by non disjunction
trisomy 21 - Downs
monosomy - Turners
in which type of conditions is gonadal mosaicism most commonly observed?
autosomal dominant
X-linked
what is gonadal mosaicism?
healthy parent has mutated germ line (in gonads)
increased chance with age
e.g Duchenne’s
parent is healthy but child may have condition
define polymorphism
non pathogenic variations at a locus from ‘wild type (normal alleles)’
what is a wild type?
normal allele
what is consanguinity?
reproductive union of 2 relatives
define penetrance
proportion of people with a particular genotype that exhibit the phenotype
define variable expression
some genotypes may be differently expressed and have different phenotypes
define genetic anticipation
wider trinucleotide repeats of mutated sequence over generations
how does genetic anticipation present? give an example of a condition
earlier and more severe disease
Huntingtons
define late onset
manifestation after birth later in life
define congenital
manifested at birth
define autozygosity
same mutation from both sides of the family
define hemizygous
genes carried on an unpaired chromosome
e.g men hemizygous for genes on Y
define lyonisation
1 female X chromosome of the 2 randomly inactivated
define genomic imprinting
Epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner
Prader-Willi Syndrome and Angelman Syndrome both caused by a mutation in the same region of chromosome but are two distinct disorders
PWS - deletion of paternal genes. Absence of active paternal genes - maternal uniparental disomy
Angelman - loss of function of maternal UBE3A due to point mutation or deletion - paternal UPD
define sex limitation
gene defect affects 1 sex only e.g BRCA-1
define allelic heterogeneity
different mutations in the same gene can cause the same condition
define dominant negative effect
a product of a faulty allele affects the healthy allele’s function
what is knudson’s two hit hypothesis?
2 faulty genes needed to cause cancer
features of autosomal dominant disease
affects those homozygous and heterozygous
affects males and females equally
affects multiple generations
name an autosomal dominant disease
Huntington’s
features of an autosomal recessive condition
only affects those homozygous for the allele
can be a carrier
skips generations
affects males and females equally
name an autosomal recessive condition
CF
features of an X-linked condition
no male to male transmission
only female carriers to to male transmission
only men can be affected
females are not affected
men cannot be carriers
(think logically about this one)
name 2 X linked conditions
Haemophilia
Duchenne’s
features of Y linked conditions
only males affected
dad to ALL sons
hat is the Hardy Weinberg equation?
p2+2pq+q2 = 1
carrier frequency of CF
1/25 (0.04)
what is carrier frequency?
The proportion of individuals in a population who have a single copy of a specific recessive genetic variant.
incidence of CF
1/2500
what is the genetic defect in CF?
delta F508
name a non traditional (non Mendelian) disease type
mitochondrial
transmission is from a mother to her children
no paternal transmission
what is a mutation?
spontaneous change in a DNA base sequence
what is a deletion?
bases removed
what is a duplication?
base repeated
what is an inversion?
DNA segment reversed
what is translocation?
exchange with non-homologous chromosome
equal or non equal
what are the two types of substitutions?
missense and nonsense
what is a missense mutation?
change in base causes a new amino acid to be coded for e.g HbA to HbS
what is a nonsense mutation?
change in base causes premature stop codon formation
UAA, UAG, UGA
types of mutation
polymorphism - non pathogenic
gene pathogenic - affects gene products (proteins)
chromosomal = whole chromosomes e.g Down’s, Edwards
what is a numerical chromosomal mutation?
alterations that affect the number of whole chromosomes
what is a structural chromosomal mutation?
translocations, deletions
are males circles or squares on pedigrees?
squares
how is a dead individual indicated on a pedigree?
line through circle or square
how are twins indicated on a pedigree?
two diagonal vertical lines from the same point
a bridge indicated they are identical
what does a diamond indicate on a pedigree?
sex unknown
how is a stillbirth indicated on a pedigree?
diamond with SB
how is a termination indicated on a pedigree
triangle with a line through it
how is a miscarriage indicated on a pedigree
triangle
how is consanguinity represented on a pedigree?
double line
what does a karyotype show?
normal chromosome configuration
what does an ideogram show?
distinct banding of chromosomes
what type of mutation causes sickle cell anaemia?
missense
a new amino acid is coded for
HbA to HbS
do the number on the arms go up or down as you approach the centromere?
up
what number is the centromere?
11.1
what is the long arm called? what does it go up to?
q arm
36.3q
what is the short arm called? what does it go up to?
petite arm (p)
22.3p
what is Turner’s syndrome
X monosomy
what is the long arm called?
q arm
what is Down’s syndrome?
trisomy 21
what is Edward’s syndrome?
trisomy 18
what is Patau’s?
trisomy 13
what is Kleinfelter’s?
XXY trisomy
do the number on the arms go up or down as you approach the centromere?
down
what is metabolism?
all intracellular reactions that take place in the body
what is the metabolic rate?
rate of intracellular reactions in the body
energy content of carbohydrates
4 kcal/g
energy content of proteins
4 kcal/g
energy content of alcohol
7 kcal/g
energy content of fat
9 kcal/g
how many g of alcohol is one unit?
how many ml of alcohol is one unit?
8g alcohol
10ml
what is the absorptive state?
the fed state
occurs after a meal when your body is digesting the food and absorbing the nutrients (catabolism exceeds anabolism)
where is fat stored? name 2
adipocytes and Ito cells
where are Ito cells found, and what is their function?
liver
store fat
how is fat stored in adipocytes?
triglyceride
where are carbohydrates stored? name 2
liver
skeletal muscle
how are carbohydrates stored?
glycogen
is protein stored in the body?
not really
what is the post absorbtive state?
the fasting state
occurs when the food has been digested, absorbed, and stored
relative levels of insulin and glucagon in the absorptive state
high insulin, low glucagon
relative levels of insulin and glucagon in the post absorptive state
low insulin, high glucagon
what is glycogenolysis?
glycogen is broken down into glucose for energy
effect of insulin on glycogenolysis
inhibits glycogenolysis
in which order are fats, carbohydrates and proteins used?
carbohydrates first, then protein, then fat
Check this one
which enzyme converts glucose to glucose 6 phosphate?
hexokinase
in the liver, the enzyme is glucokinase
which enzyme converts glucose 6 phosphate to fructose-6-phosphate?
phosphoglucose isomerase
which enzyme converts fructose 6-phosphate to fructose 1,6-bisphosphate?
phosphofructokinase-1
PFK-1
which is the rate limiting step of glycolysis?
fructose-6-phosphate to fructose 1,6-bisphosphate
by PFK-1
which two products can fructose 1,6-bisphosphate be converted into?
dihydroxyacetone phosphate or glyceraldehyde 3-phosphate (G-3-P)
they are reversible products of each other
which enzyme converts fructose 1,6 bisphosphate to its products?
aldolase
which product of fructose 1,6 bisphosphate is all of the product converted to?
G-3-P
which enzyme converts dihydroxyacetone phosphate to G-3-P?
triose phosphate isomerase
which enzyme converts G-3-P to 1-3 bisphosphoglycerate?
G-3-P dehydrogenase
which enzyme converts 1-3 bisphosphoglycerate to 3-phosphoglycerate?
phosphoglycerate kinase
which enzyme converts 3-phosphoglycerate to 2-phosphoglycerate?
phosphoglycerate mutase
which enzyme converts 2-phosphoglycerate to phosphoenolpyruvate?
enolase
which enzyme converts phosphoenolpyruvate to pyruvate?
pyruvate kinase
net yield of glycolysis?
2 pyruvate
2NADH
2ATP
which steps of glycolysis produce ATP?
1-3 bisphosphate to 3 phosphoglycerate
and
phosphoenolpyruvate to pyruvate
does insulin increase or decrease the rate of glycolysis?
increase
affects PFK-1
what are the major and minor regulators of glycolysis?
minor - hexokinase ativity controlled by G6P
major - PFK-1 allosterically
how does glucose 6 phosphate affect hexokinase?
inhibits
how is PFK-1 affected by AMP?
an increase in AMP increases PFK action
how is PFK-1 affected by ATP?
as ATP increases, PFK activity decreases
inhibited by ATP
list the substance in each step of glycolysis
good guys feed farm ducks grain, barley 4Ps
glucose
glucose-6-phosphate
fructose-6-phosphate
fructose 1,6-bisphosphate
dihydroxyacetone phosphate
glyceradehyde-3-phosphate
1-3 bisphosphoglycerate
3-phosphoglycerate
2-phosphoglycerate
phosphoenolpyruvate
pyruvate
is glycolysis anaerobic or aerobic?
anaerobic
where does glycolysis take place?
cytoplasm
products of anaerobic respiration
lactate and NAD+, and little ATP
NAD+ allows glycolysis to continue
describe the structure of ATP
high energy molecule composed of:
adenine
ribose sugar
three phosphate groups
high energy phosphoanhydride bonds between phosphates
describe the process of glycolysis
Preparative/ energy investment phase
Glucose → glucose-6-phosphate
Requires 1 ATP
Catalysed by hexokinase
Glucose-6-phosphate → fructose-6-phosphate
Catalysed by phosphoglucoisomerase
Fructose-6-phosphate → fructose-1,6-bisphosphate
Requires 1 ATP
Catalysed by phosphofructokinase
Inhibited by ATP, activated by AMP
Fructose-1,6-bisphosphate → 2 x glyceraldehyde-3-phosphate
ATP generating phase
From here on, there are actually 2 reactants and products in total. Ie, one glucose molecule produces 2 pyruvates
Glyceraldehyde-3-phosphate → 1,3-bisphosphoglycerate
2 NADH + 2H+ produced
Triose phosphate dehydrogenase
1,3-bisphosphoglycerate → 3-phosphoglycerate
Produces 2 ATP
Phosphoglycerokinase
3-phosphoglycerate → 2-phosphoglycerate
Phosphoglyceromutase
2-phosphoglycerate → phosphoenolpyruvate
Enolase
Produces water
phosphoenolpyruvate → pyruvate
Creates 2 ATP
pyruvate kinase
give the equation for glycolysis
Glucose + 2NAD+ + 2Pi + 2 ADP → 2 pyruvate + 2NADH + 2H+ + 2 net ATP + 2H2O
function of a kinase enzyme
adds/ removes phosphate group
function of an isomerase enzyme
rearranges structure of substrate without changing molecular formula
similar to mutase
function of an aldolase enzyme
creates or breaks carbon-carbon bonds
function of a dehydrogenase enzyme
moves hydride ion to an electron acceptor e.g NAD+
function of an enolase enzyme
produces a carbon to carbon double bond by removing a hydroxyl group (OH)
function of a mutase enzyme
moves a functional group in a molecule
how is pyruvate converted to acetyl CoA?
link reaction in the matrix:
pyruvate (3C) + NAD + CoA → acetyl CoA (2C) + carbon dioxide + NADH
why can’t anaerobic respiration continue indefinitely?
lactic acid build up is harmful
substrates of the TCA cycle
can I keep some succinate for my oxaloacetate?
citrate
isocitrate
alpha ketoglutarate
succinyl CoA
succinate
fumarate
malate
oxaloacetate
name the enzymes of the TCA cycle
citrate and isocitrate keep some substrate for my oxaloacetate!
citrate synthase
aconitase
isocitrate dehydrogenase
alphaketoglutarate dehydrogenase
succinyl CoA synthetase
succinate dehydrogenase
fumarase
malate dehydrogenase
draw the TCA cycle
ensure all enzymes and byproducts are present
name the rate limiting enzymes of the TCA cycle
citrate synthase
isocitrate dehydrogenase
a-ketoglutarate dehydrogenase
how is citrate synthase inhibited and activated?
inhibited:
allosterically by ATP and NADH
competitively by succinyl CoA
activated by ADP
which is the main rate limiting enzyme o
isocitrate dehydrogenase
how is isocitrate dehydrogenase activated or inhibited?
Activated by ADP
Inhibited by ATP, NADH
how is alphaketoglutarate dehydrogenase activated or inhibited?
inhibited by ATP, NADH, succinyl CoA, GTP
aim of the Krebs cycle
produce NADH and FADH2 for oxidative phosphorylation
products of the Krebs cycle per GLUCOSE molecule
6 NADH
2 FADH2
2 GTP
where else can we obtain acetyl CoA from?
beta oxidation of fatty acids
where else can we obtain alpha ketoglutarate from?
oxidative determination of glutamate
reverse transamination of glutamate and pyruvate
describe the process of oxidative phosphorylation
NADH to complex 1 of ETC
FADH2 to complex 2 of ETC
they deposit H+ and e- and are oxidised
NAD+ and FADH return to glycolysis and TCA cycle
energy from electron transport chain is used to pump H+ across matrix into inter membrane space
this establishes an electrochemical gradient
electrons are transferred to molecular oxygen, which splits in half and takes up H+ to form water
complex 4 is where oxygen is reduced to water
as H+ flow down their gradient into the matrix, they pass through ATP synthase which synthesises ATP
where does TCA cycle occur?
mitochondrial matrix
where do the ETC and oxidative phosphorylation occur?
inner mitochondrial membrane
what is the final electron acceptor?
oxygen
give the equation for the formation of water in the ETC
O2 + 4H+ 4e- → 2H2O
how many ATP per glucose molecule?
30-34
what must happen to fatty acids before they can be oxidised in mitochondria
activated in the cytoplasm
converted to acyl CoA
what process takes acyl CoA with more than 14 carbons through the mitochondrial membrane?
carnitine shuttle
what is the end product of fatty acid beta oxidation?
acetyl CoA
what is most of the acetyl CoA generated by fatty acid activation used for?
what is a small proportion used for?
TCA cycle
converted into ketones
maximum number of carbons that acyl-CoA can have and diffuse through the mitochondrial membrane
12
explain fatty acid activation, oxidation and utilisation in simple terms
(collectively fatty acid metabolism)
activation:
fatty acids converted to acyl adenylate (ATP to ADP) then acyl CoA in the cytoplasm
acyl CoA enters mitochondria by carnitine shuttle
oxidation:
acyl CoA converted to acetyl CoA in mitochondrial matrix
utilisation:
acetyl CoA is used in the TCA cycle or to make ketones
where are fatty acids activated?
cytoplasm
what is the product of activation of fatty acids?
acyl CoA
how does acyl CoA enter mitochondria if it is large?
carnitine shuttle
where is acyl CoA converted to acetyl CoA?
mitochondrial matrix
what is the rate limiting step of beta fatty acid oxidation?
carnitine shuttle
where else does beta oxidation occur?
peroxisomes
when does ketogenesis occur?
when there is excess acetyl CoA that is not used in TCA cycle
when there is an excess, what is acetyl-CoA converted to?
acetate, acetoacetate, beta-hydroxybutyrate - ketone bodies
what happens to ketone bodies when fuel runs low?
converted back into acetyl CoA to enter TCA cycle
what is diabetic ketoacidosis?
an increase in ketone concentration in blood
high blood glucose
an increase in blood acidity which affects haemoglobin performance in terms of its ability to bind to oxygen
what is the brain’s main fuel?
glucose, but can adapt to use ketones
can the liver use ketones as fuel? why
no
does not have the enzyme to convert ketones to Acetyl CoA
what is the predominant blood buffering system?
bicarbonate buffer system
when are fatty acids synthesised?
high ATP levels inhibit TCA
build up of acetyl CoA
where does fatty acid synthesis occur?
cytoplasm
can acetyl CoA cross mitochondrial membranes?
no
what is the range of normal blood pH?
7.35-7.45 pH
equation for blood buffer
CO2 + H2O ⇄ H2CO3 ⇄ HCO3- + H+
function of carbonic anhydrase
convert carbon dioxide and water to carbonic acid
fate of carbonic acid
dissociates into hydrogencarbonate ions and protons
which two substance form the buffer? which is the acid, and which is the base?
carbonic acid (acid) and hydrogen carbonate ions (base)
w are CO2, protons and HCO3- regulated?
CO2 is regulated by breathing
protons and HCO3- are renally regulated
general henderson hasselbach equation
pH = pKₐ + log10([A⁻]/[HA])
henderson hasselbach equation for the carbonic acid/ bicarbonate system
pH = 6.1 + log10([HCO3⁻]/0.03[CO2])
or
pH = 6.1 + log10(25mM/0.03[40mmHg])
0.03 is a proportionality constant for CO2 which converts the partial pressure in mmHg into a concentration in solution which in turn equates into a H2CO3 concentration
how is the efficiency of bicarbonate as a buffer improved?
carbon dioxide is removed at the lungs
bicarbonate is regenerated at the kidneys
functions of haemoglobin
oxygen transport
carbon dioxide transport to lungs (carbaminohaemoglobin)
mops up excess H+ as a buffer
NO transport around body for vasodilation
equation for oxygen transport using haemoglobin
Hb + O2 ⇄ HbO2
equation for carbon dioxide transport using haemoglobin
Hb + CO2 ⇄ HbCO2
equation for hydrogen reacting with haemoglobin
Hb + H+ ⇄ HbH
what is acidosis?
pH is lower than 7.35
what is alkalosis?
pH is greater than 7.45
what is response to acidosis or alkalosis called?
compensation
what are two types of acidosis and alkalosis?
respiratory and metabolic
what is an ABG?
arterial blood gas measurement
definition of metabolic acidosis
low pH
low HCO3-
ROME - respiratory, opposite, metabolic, equal
compensation for metabolic acidosis
deep hyperventilation to decrease arterial pCO2
definition of metabolic alkalosis
high pH and high HCO3-
compensation of metabolic alkalosis
hypoventilation and renal HCO3- excretion to increase arterial pCO2
definition of respiratory acidosis
low pH
high carbon dioxide
compensation for respiratory acidosis
increase in renal HCO3- retention
definition of respiratory alkalosis
high pH
low CO2
compensation for respiratory alkalosis
increase in excretion of HCO3-
what is the anion gap?
anions - cations
([Na+] + [K+])-([Cl-] - [HCO3-])
normal range of values for anion gap
4-12mmol/L
what are reactive oxygen species?
highly reactive oxygen containing compounds that are free radicals
is hydrogen peroxide a radical?
no, but can be decomposed in chains of reactions
name two reactions in which hydrogen peroxide is decomposed
Fenton
Heber-Weiss
name protections from ROS
cellular components
antioxidant vitamins e.g E,C
what are ROS key in?
respiratory burst
immunological defence mechanism
phagocytes release ROS to hydrolyse foreign material
name conditions associated with high ROS levels
diabetes
Parkinsons
renal failure
difference between mitosis and meiosis
meiosis
- only in gametes
- recombination of genetic material for diversity
- two cell divisions
- 4 haploid daughter cells
how long will body glycogen levels last?
12 hours
