IMMS Flashcards
1
Q
<p>cell membrane structure and contents</p>
A
<p>phospholipid bilayer
cholesterol - supports fluidity
proteins - act as transporters
glycolipids and glycoproteins - involved in cell signalling</p>
2
Q
<p>cell membrane functions</p>
A
<p>semi-permeable membrane
cell membrane receptors
regulates what goes in and out of cell
separates intracellular cell contents from extracellular</p>
3
Q
<p>tight junction function</p>
A
<p>seals neighbouring cells together in epithelial sheet to prevent leakage of molecules between them</p>
4
Q
<p>adherent junction function</p>
A
<p>joins an actin bundle in one cell to a similar bundle in a neighbouring cell</p>
5
Q
<p>desmosome function</p>
A
<p>joins intermediate filaments in one cell to those in a neighbour</p>
6
Q
<p>gap junction function</p>
A
<p>allows passage of small water-soluble ions and molecules</p>
7
Q
<p>hemidesmosome function</p>
A
<p>anchors intermediate filaments in a cell to the basal lamina</p>
8
Q
<p>hormones - peptide vs steroid</p>
A
<p>steroid - slow response (sex hormones)
peptide - fast response (insulin, TSH)</p>
9
Q
<p>homeostasis definition</p>
A
<p>the maintenance of a constant internal environment</p>
10
Q
<p>types of cell signalling</p>
A
<p>autocrine
paracrine
endocrine
exocrine</p>
11
Q
<p>water distribution in the body</p>
A
<p>2/3 intracellular - 28L
| 1/3 extracellular -14L</p>
12
Q
<p>components of extracellular fluid</p>
A
<p>plasma - 3L
transcellular - 1L
interstitial - 10L</p>
13
Q
<p>contents of ECF </p>
A
<p>glucose, urea, Cl-, HCO3-
main cation in Na+</p>
14
Q
<p>contents of ICF</p>
A
<p>main cation is K+</p>
15
Q
<p>osmolality definition</p>
A
<p>concentration of solutes in plasma per kilogram of solvent</p>
16
Q
<p>osmolarity definition</p>
A
<p>concentration of solutes in plasma per litre of solution</p>
17
Q
<p>osmotic pressure definition</p>
A
<p>the pressure that would have to be applied to a pure solvent to prevent it from passing into a given solution by osmosis
measure of how easily a solution can take in water
</p>
18
Q
<p>oncotic pressure</p>
A
<p>form of osmotic pressure induced by proteins, notably albumin, in a blood vessel's plasma that displaces water molecules, thus creating a relative water molecule deficit with water molecules moving back into the circulatory system within the lower pressure venous end of capillaries
</p>
19
Q
<p>oedema definition</p>
A
<p>increased movement of fluid from plasma into interstitial space</p>
20
Q
<p>monosaccharide definition</p>
A
<p>any sugar that can't be hydrolysed</p>
21
Q
<p>types of monosaccharides</p>
A
<p>glucose, fructose, galactose</p>
22
Q
<p>oligosaccharide definition</p>
A
<p>substance made of 3-10 monosaccharides</p>
23
Q
<p>polysaccharide definition</p>
A
<p>complex carbohydrate composed of more than 10 monosaccharides joined by glycosidic bonds</p>
24
Q
<p>formation of glycosidic bonds</p>
A
<p>condensation reaction of 2 monosaccharides water is by-product</p>
<p><br></br>
</p>
25
lipid structure
3 fatty acids bound to one glycerol
26
amino acid structure
amino group (NH2) and carboxyl group (COOH) bound to carbon with H and side chain
27
structures of proteins
primary, secondary, tertiary, quaternary
28
primary protein structure
sequence of a chain of amino acids
held together by peptide bonds (CONH)
29
secondary protein structure
local folding of polypeptide chain into alpha helices or beta pleated sheet
alpha helix - hydrogen bond from NH to CO 3-4 residues earlier
beta strands connected laterally by 3-4 backbone hydrogen bonds
30
tertiary protein structure
3D folding pattern of a protein due to side chain interactions
disulfide bonds, hydrogen bonds, salt bridges, non-polar hydrophobic interactions
31
quaternary protein structure
more than one aa chain
32
ATP-ADP cycle
ATP + water -> ADP + Pi + energy for cells
ADP + Pi + energy from food -> ATP
33
metabolism definition
chemical reactions that occur in a living organism
34
BMR definition
Basal Metabolic Rate
measure of energy required to maintain non-exercise bodily functions
35
example of BMR
respiration/biosynthesis - only measured if not eaten in past 12 hours, controlled temperature
36
what is oxidative phosphorylation?
electron transport chain
37
where does oxidative phosphorylation occur?
inner mitochondrial membrane
38
what happens in oxidative phosphorylation?
H+ pumped into intermembrane space via proton pumps to form electrochemical gradient
electrons transferred to 02 to split to form water
39
where do electrons come from in oxidative phosphorylation?
NADH -> NAD+ + e-
| FADH2 -> FAD + e-
40
how many ATPs produced per NADH/FADH?
3 and 2, respectively
41
how much ATP is produced per molecule of glucose?
34
42
how is ATP formed in oxidative phosphorylation?
H+ ions flow down electrochemical gradient through ATP synthase to form ATP
43
fatty acid oxidation definition
production of ATP from fat consumption (diet) and fat storage using beta oxidation
44
examples of fatty acids
linoleic acid, oleic acid, palmitic acid, arachidonic acid
45
where can acetyl-CoA be derived from?
beta oxidation of fatty acids
fatty acid has to be activated first to form acyl-CoA
acyl-CoA enters carnitine shuttle to enter mitochondria for beta oxidation
46
pathology of fatty acid oxidation
diabetic ketoacidosis
47
multifactorial disease
spina bifida
diabetes
schizophrenia
48
environmental diseases
poor diet
| infection
49
categories of diseases
genetic, multifactorial, environmental
50
what is gametogenesis?
first stage is the proliferation of primordial germ cells by mitosis
timing of mitosis differs in males and females
51
primary spermatocytes
some mitosis occurs in embryonic stages to produce primary spermatocytes at birth
52
gametogenesis in males
mitosis begins in puberty, throughout life
cytoplasm divides evenly
four equal size gametes
millions of mature sperm continually produced
53
how long does male gametogenesis take?
60-65 days
54
when does meiosis occur in oogonia?
prophase 1 by 8th month of intrauterine life
55
when do cells enter ovulation?
10-50 years later
56
how does the cytoplasm in female gametogenesis divide?
unequally - 1 egg and 3 polar bodies (apoptose - go on to die)
57
when does meiosis 1 occur?
completed at ovulation. one big cell and one small, diploid DNA
58
when is meiosis 2 completed?
if fertilisation occurs
59
what is non-disjunction? what can it lead to?
failure of chromosome pairs to separate in meiosis 1 or sister chromatids to separate properly in meiosis 2
downs syndrome/monosomy (Turners syndrome)
60
what is monosomy?
loss of a chromosome
61
what is Turners syndrome?
only 1 X chromosome
62
what is the karyotype?
number and appearance of chromosomes in a cell
spreads arranged in size order, biggest is pair 1 and smallest is pair 22
63
hwo many bp are in a chromosome?
10^7
64
how many genes do we have?
30000
65
structure of chromosome
long arm (q) and short arm (p - petit)
separated by centromere
66
what is monosomy?
loss of chromosome
67
what is Turner's syndrome?
only 1 X chromosome
68
what can problems with meiosis lead to?
non disjunction
downs, monosomy
69
what is non-disjunction?
failure of chromosome pairs to separate in meiosis 1 or sister chromatids to separate in meiosis 2
70
what is downs syndrome?
trisomy 21
71
what is gonadal mosaicism?
precursor germline cells to ova or spermatozoa are a mixture of 2+ genetically different cell lines (error in mitosis)
72
who does gonadal mosaicism affect?
advancing paternal age
parent healthy, fetus maybe affected
more common in males
any inheritance pattern, more common in autosomal dominant and X-linked
73
why does lyonisation occur?
to prevent female cells from having twice as many gene products from the x chromosome as males
74
what is the barrbody?
inactive X chromosome since packaged in heterochromatin
75
what is imprinting?
non-mendelian
for some genes only 1/2 alleles is active, the other is inactive for some it's always maternal/paternal allele
76
what is Knudson's 2-HIT hypothesis?
gene mutations may be inherited or acquired during a person's life
77
what are sporadic cancers?
2 acquired mutations
78
what are hereditary cancers?
1 inherited mutation and 1 acquired mutation
79
what is an ideogram?
diagrammatic form of chromosome bands - bands are numbered according to distance to centromere
80
classification of genetic disease
chromosomal, mendelian (autosomal dominant/recessive or X-linked), non-traditional (mitochondrial)
81
where is mitochondria inherited from?
mother
82
what is the general formula of carbohydrates?
Cn(H2O)n
83
what is lactose made of?
glucose + galactose
84
what is sucrose made of?
glucose + fructose
85
what is maltose made of?
glucose + glucose
86
what is a monosaccharide?
chain of carbons, hydroxyl group, one carbonyl group
87
D + L monosaccharides
same chemical properties but different biological ones
optically active and different forms
most are D in living organisms
88
what are ring structures?
cyclised
reaction of aldehyde/ketone group with hydroxyl group of same molecule
89
what is a glycosidic bond?
hydroxyl group of a monosaccharide reacts with an OH or NH group
90
what do O-glycosidic bonds form?
disaccharides, oligosaccharides, polysaccharides
91
what do N-glycosidic bonds form?
nucleotides and DNA
92
what are disaccharides?
2 monosaccharides joined by an O-glyosidic bond
93
what is starch?
storage in plants
made of amylose (glucose alpha 1,4) and amylopectin (glucose alpha 1,4 and alpha 1,6 bonds)
94
what are proteoglycans?
long, unbranched polysaccharides radiating from a core protein
found in animals
95
what is glycogen?
storage in animals
branched polysaccharide formed of glucose residues
alpha 1,4 (between carbons and alpha 1,6 (side chain and main chain)
branching at regular intervals
core protein is glycogenic
96
what are properties of peptide bonds?
very stable
cleaved by proteolytic enzymes - proteases or peptidases
partial double bonds
flexibility around C atoms not involved in bond
97
regulation of enzymes
altering conc. of substrates, products, inhibitors or activators, or modifying enzyme by phosphorylation
98
what is an isoenzyme?
enzymes w/ different structure and sequence, catalyse same reaction
99
what are coenzymes?
cannot catalyse a reaction themselves, but help enzymes do so.
bind w/ enzyme protein molecule to form active enzyme
100
what is the process of DNA transcription?
transcription complex forms around TATA box on 5' of 1st exon
topoisomerase unwinds double helix by relieving supercoils
DNA helicase separates DNA, exposing nucleotides
SSBs coat strands to prevent reannealing
free mRNA nucleotides line up their complementary bases on template/antisense strand
RNA polymerase 2 joins mRNA nucleotides to form antiparallel mRNA strand starting at promoter
mRNA leaves nucleus and attaches to 8Os ribosome
101
oxidation-reduction coenzymes
involved in reactions where electrons are transferred from one compound to the other
102
what is myoglobin?
porphyrin ring - iron atom
muscle, reserve supply of oxygen, facilitates movement of O2 in muscles
103
specificity of antibody-antigen binding
one antibody matches only one antigen
104
what are antigens bound by?
portion of antibody called variable domain
105
what is the primer?
short strand of DNA that's the start point for DNA synthesis as DNA polymerases can only add nucleotides onto an existing strand of DNA
106
what is the SSB?
single strand binding protein
keeps 2 strands of DNA apart while synthesis of new DNA occurs
prevents annealing to form double stranded DNA
107
what is the primase enzyme?
RNA polymerase that synthesises the short RNA primers needed to start strand replication process
108
what is RNAse H?
removes RNA primers that previously began DNA strand synthesis
109
what are transcription factors?
proteins which bind to promotor regions
110
what is the promoter?
5' of 1st exon
111
what is the TATA box?
reads thymine, adenine, etx
112
what is the structure of the antiparallel mRNA strand?
5' CAP head and 3' Poly A tail
113
what does mRNA attach to after leaving the nucleus?
80s ribosome
114
what does the mRNA do at the ribosome?
mRNA sequence used as template to bind to complementary tRNA molecules at anticodon (3 bases complementary to codon on mRNA)
115
what codes for a particular amino acid?
one codon
116
where is the amino acid carried by the tRNA?
on its 3' end
117
how are bases read?
5' to 3'
118
how are proteins created?
enzymes remove amino acid from tRNA and amino acids linked together by a peptide bond (condensation) - creating polypeptide chain
119
what is the start codon?
AUG
120
what are the stop codons?
UGA, UAG, UAA
121
how does a ribosome recognise mRNA?
from its CAP on the 5' end
122
what are the exons?
contain the coding sequence
123
what is the promoter region?
what RNA polymerase recognises and where it starts
124
primary -> mature
non-coding introns are removed and exonic regions are joined
125
what is exon shuffling?
exons not in same order
allows new proteins to be made
huge variants of antibodies to produce
126
gene for producing immunoglobulins in macrophage vs B cell
macrophage (not produced) - in heterochromatin form
B cell (produced) - euchromatin form
127
out of frame deletion
clearly disrupts protein - shifts, meaning the reading frame of the gene is changed
catastrophic effects, early mortality
128
in frame deletion
complete codon is removed - only one amino acid is lost
less catastrophic
reading frame is not altered
milder disease, later onset death
129
mutations of regulatory sequence
coding sequence still intact but gene itself is switched on or off
130
DNA damage/repair issues
chemicals, UV, radiation
base/nucleotide excision, mismatch repair, transcription-coupled repair
131
mis sense mutation
A point mutation in which a single nucleotide change results in a codon that codes for a different amino acid (substitution). This can have a varied affect and can result in a silent mutation and a non functional protein
132
missense mutation in sickle cell disease
CAG replaced with CTG
133
nonsense mutation
Point mutation that produces a stop codon - results in an incomplete, usually non-functional protein. E.g. Duchenne’s muscular dystrophy
134
splice-site mutation
affects accurate removal of an intron
excision doesn't occur as enzyme doesn't recognise cutting site, sequence of intron is translated
135
expansion of a tri-nucleotide repeat (e.g. Huntingtons)
triple repeat repeated several times in first part of coding sequence
normal range is 15-20
repeats 36+ Huntingtons, earlier onset
<36 -> no disease
Huntingtons: CAG
136
anticipation
repeats get bigger when transmitted to next generation -> earlier symptoms of greater severity
137
types of communication
autocrine, paracrine, endocrine, exocrine
138
autocrine
chemical released from cell into ECF, acts upon cell that secreted it
139
paracrine
messengers involved in communication between cells, released into ECF - short distances, local communication
140
differences between endocrine and paracrine
hormone travel in blood in endocrine, in paracrine only in ECF
endocrine affects more things and travels further
141
primary hypothyroidism
thyroid producing too little thyroxine to induce negative feedback - TSH levels in blood keep increasing as pituitary doesn't think theres enough
142
primary hyperthyroidism
thyroid produces too much thyroxine and keeps producing regardless of TSH produced by pituitary, TSH falls, thyroxine rises
143
types of hormones
peptide, steroid and amino-acid derivative
144
what are peptide hormones made of?
short chain amino acids - vary in size
carbohydrate side chains (glycoproteins)
they are large hydrophilic charged molecules that can't diffuse across a membrane
145
what are the properties of peptide hormones? how do they get across membranes?
large, hydrophilic charged molecules
cannot diffused across membrane - bind to receptors on it
146
how are peptide hormones made/released?
premade and stored in cell, then released and dissolved into blood when needed
147
how quickly do peptide hormones react? what is their response?
chemical reaction produces quick response from the cell
2nd messenger released - very fast (signal transduction cascade)
148
examples of peptide hormones
insulin, growth hormone, thyroid stimulating hormone, ADH/vasopressin
149
what is steroid hormone synthesised from?
synthesised from cholesterol, water, insoluble and soluble lipid
150
how do steroid hormones cross membranes?
can cross
transport proteins in blood
targets intracellular receptor
151
how is steroid hormone made/released?
made by cell
diffuses out once made (not stored)
152
how is steroid hormone transported in the blood?
bound to transport proteins cannot dissolve in water
153
what receptor does steroid hormone bind to?
receptor inside cell
154
how quick is the steroid hormone response? what is its effect?
slow (hours/days) - directly affects DNA
155
examples of steroid hormones
testosterone, oestrogen, cortisol
156
what are the effects of angiotensin II and aldosterone?
increase Na+ reabsorption in kidneys in exchange for potassium or hydrogen excretion
stimulate ADH release
157
what are examples of amino acid hormones?
adrenaline, thyroid hormones (thyroxine (T4) and triiodothyronine (T3))
158
interstitial fluid
surrounds the cells, doesn't circulate
159
transcellular fluid
makes up CSF, digestive juices, mucus
160
plasma
circulates as the extracellular component of blood
161
where is water taken in/lost from?
diet, drink, IV fluid
kidneys, insensible losses (sweat, breath, vomiting, faeces)
162
what is osmosis?
net movement of solvent molecules through a semipermeable membrane to a higher solute concentration (lower water conc.)
163
what is hydrostatic pressure?
pressure difference between capillary blood (plasma) and interstitial fluid - water and solutes move from plasma into interstitial fluid
164
what happens when water is lost from ECF?
increase in solutes/decrease in water = increase in osmolality in ECF
osmoreceptors in hypothalamus detect this
-> ADH/vasopressin release from posterior pituitary
ADH increases water reabsorption
165
what happens when there is decreased renal blood flow?
decrease in water in ECF = decrease in effective circulating volume
release of renin from juxtaglomerular cells in kidneys
renin converts angiotensinogen to angiotensin I, ACE converts it to angiotensin II, triggering release of aldosterone from adrenal cortex
166
what releases aldosterone? what is it triggered by?
adrenal glands (cortex)
angiotensin II
167
what are the effects of angiotensin II and aldosterone?
increase Na+ reabsorption in kidneys in exchange for potassium or hydrogen excretion
168
how does sodium resorption affect water?
brings water with it
169
causes of dehydration
water deprivation, vomiting, burns, heavy sweating, diabetes insipidus, diabetes mellitus, drugs
170
consequences of dehydration
thirst, dry mouth, inelastic skin, sunken eyes, raised hematocrit, weight loss, confusion, hypertension
171
causes of water excess
high intake, decreased loss of water, excess ADH
172
consequences of water excess
hyponatraemia, cerebral overperfusion, headaches, confusion, convulsions
173
what is serous effusion?
excess water in a body cavity
174
what is hypernatraemia? what are its causes and consequences?
high sodium
renal failure, mineralocorticoid excess, osmotic diuresis (increased urine rate due to high water amount), diabetes insipidus
cerebral intracellular dehydration, lower water conc,
175
what is hyponatraemia? what are its causes and consequences?
low sodium
diuresis (increased urine rate), Addison's disease, excess IV fluids and oedema
intracellular over hydration - hypotension
176
what is potassium excretion from the kidney controlled by?
aldosterone - controls Na/K pump
177
what is hyperkalaemia? what are its causes and consequences?
high potassium
renal failure, diuretics/ACE inhibitors, Addison's, acidosis
risk of myocardial infarction - mess w/ resting potential in heart
178
what is hypokalaemia? what are its causes and consequences?
low potassium
diarrhoea, vomiting, alkalosis, hypomagnesaemia
weakness and cardiac dysrhythmia
179
what is hypercalcaemia? what are its causes and consequences?
high calcium
primary hyperparathyroidism (too much parathyroid hormone, calcium leached from bone to increase blood levels), skeletal metastases, vit D toxicity, TB
metastatic calcification, kidney stones (renal calculi)
180
what is metastatic calcification?
deposition of calcium salts in otherwise normal tissues
stones
181
what is hypocalcaemia? what are its causes and consequences?
low calcium
vit D deficiency, magnesium deficiency, renal disease, parathyroidectomy, intestinal malabsorption
consequences: tetany
182
what is tetany?
spasms of the hands, feet and voice box
183
what is facilitated diffusion?
movement of solutes from a region of high conc to low conc through protein channels (w/out carrier proteins)
continues until dynamic equilibrium is reached
184
what is active transport? what does it require?
movement of solutes from a region of low conc. to high conc. against the conc. gradient
transmembrane carrier protein and ATP required
185
what is a receptor?
a specific protein in either the plasma membrane or the interior of a target cell that a chemical messenger binds with - invokes a biologically relevant response
186
what is specificity?
ability of a receptor to bind only one type/limited number of structurally related types of chemical messengers
187
what is saturation?
the degree to which receptors are occupied by messengers
188
what is affinity?
the strength with which a chemical messenger binds to its receptor
189
what is competition?
the ability of different molecules to compete with a ligand for binding to its receptor. competitors usually similar in structure
190
what is an antagonist?
a molecule that competes with a ligand for binding to its receptor but doesn't activate signalling normally associated with it
prevents actions of the natural ligand
191
what is an example of an antagonist?
antihistamines
192
what is an agonist?
a chemical messenger that binds to a receptor and triggers the cell's response
drug that mimics a normal messenger's action
193
what is an example of an agonist?
decongestants
194
what is down-regulation?
a decrease in total number of target-cell receptors for a given messenger - may occur due to chronic high extracellular conc. of messenger
195
what is up-regulation?
an increase in the total number of target-cell receptors for a given messenger - may occur due to chronic low extracellular conc.
196
what is increased sensitivity?
increased responsiveness of a target cell to a given messenger - may result from upregulation
197
what is the main cause of down-regulation?
internalisation - taken into cell by receptor mediated endocytosis
increases rate of receptor degradation
198
what is receptor activation?
combination of messenger with receptor causing change in conformation of the receptor
199
what are potential cell reactions to the messenger?
changes in the permeability, transport properties or electrical state of the plasma membrane
changes in metabolism, secretory activity, rate of proliferation/differentiation, contractile activity
200
what are signal transduction pathways?
diverse sequences of events linking receptor activation to cellular responses
201
what do the lipid-soluble messengers do in the nucleus?
acts as a transcription factor
binds to DNA at a regulatory region of a gene - increases rate of transcription
202
effects of cortisol
inhibits transcription of genes whose protein products mediate inflammatory responses following injury/infection
lipid-soluble
203
what are first messengers?
extracellular chemical messengers that reach the cell and bind to specific plasma membrane receptors
204
what are second messengers?
substances that enter/generated in cytoplasm due to receptor activation by 1st messenger
205
what is a protein kinase?
enzyme that phosphorylates other proteins by transferring a phosphate group to them from ATP
206
what underlies the cell's biochemical response to the first messenger?
ultimate phosphorylation of key proteins, e.g. transporters, metabolic enzymes, ion channels, contractile proteins
207
what are protein phosphatases?
dephosphorylate proteins
208
ligand-gated ion channels
activation of receptor by first messenger (ligand) -> conformational change of the receptor -> forming an open channel through plasma membrane
209
where are ligand-gated ion channels prominent?
plasma membranes of neurons
210
what does opening of the ligand-gated ion channels lead to?
increase in net diffusion of ions across membrane - changes membrane potential
211
types of plasma membrane receptors
ligand gated ion channels
receptors that function as enzymes
receptors that are bound to and activate cytoplasmic janus kinases
G-protein-coupled receptors
212
what are receptor tyrosine kinases?
many receptors with intrinsic enzyme activity are protein kinases, majority specifically phosphorylate tyrosine residues
213
what is the sequence of events for receptors w/ intrinsic tyrosine kinase activity?
binding changes receptor so its enzymatic portion, on cytoplasmic side, is activated
leads to autophosphorylation of the receptor
phosphotyrosines on cytoplasmic portion of the receptor serve as docking sites for cytoplasmic proteins
bound docking proteins bind and activate proteins, which activate signalling pathways
214
what is autophosphorylation?
receptor tyrosine kinases phosphorylates some of its own tyrosine residues - creates phosphotyrosines on cytoplasmic side
215
what do phosphotyrosines do?
(on cytoplasmic side) docking sites for cytoplasmic proteins which activate signalling pathways
216
what catalyses the formation of cGMP
a receptor acting as a receptor and as a guanylyl cyclase catalyses the formation in cytoplasm
217
what does cGMP do?
acts as a 2nd messenger to activate a protein kinase called cGMP-dependent protein kinase
218
what does cGMP-dependent protein kinase do?
phosphorylates specific proteins that mediate the cell's response to the original messenger
219
where are receptors that function as ligand-binding molecules and guanylyl cyclases predominant?
retina of eye - processing visual inputs
220
what happens when guanylyl cyclase enzymes are in the cytoplasm?
first messenger, NO, diffuses into cytosol of the cell to trigger the formation of cGMP
221
what is NO? what is it produced by?
lipid-soluble gas
amino acid gas arginine by enzyme nitric acid synthase (present in cell types)
222
in what way does NO act?
paracrine
223
what are JAKs?
janus kinases - family of separate cytoplasmic kinases associated with the receptor
224
process in JAKs
acts as a functional unit with receptor
binding of first messenger -> conformational change -> activation of janus kinase
225
what do different JAKs do?
phosphorylate different target proteins, many acting as transcription factors
synthesise new proteins
226
what are cytokines?
proteins that are secreted by cells of the immune system that play a critical role in immune defences
227
what are G proteins?
family of proteins bound to inactive receptor on cytosolic surface of plasma membrane
3 subunits
228
what are the subunits of G proteins? what do they do?
alpha, beta and gamma subunits
alpha subunit can bind GDP and GTP
beta and gamma subunits help anchor alpha subunit in the membrane
229
what does the activated receptor associated with G proteins do?
increases the affinity of alpha subunit of G protein for GTP
when bound to GTP, the alpha subunit dissociates from the beta and gamma subunits of the trimeric G protein
allows it to link up with another plasma membrane protein - ion channel or enzyme
230
what effects can the G protein have?
may cause ion channel to open -> change in electrical signals
activate/inhibit membrane enzymes - may generate second messengers
231
what happens once the alpha subunit of the G protein activates its effector protein?
GTPase activity inherent in alpha subunit cleaves the GTP to GDP and Pi
makes alpha subunit inactive, recombines with beta and gamma subunits
232
what inactivates alpha subunits? what does this lead to?
GTPase activity inherent in alpha subunit cleaves GTP to GDP and Pi
recombine with beta and gamma subunits
233
what are the most common effector protein enzymes regulated by G proteins?
adenylyl cyclase and cyclic AMP
234
what is the G protein in the adenylyl cyclase/cAMP pathway?
Gs (stimulatory)
235
what is the effector protein of Gs?
adenylyl cyclase (membrane enzyme)
236
what does adenylyl cyclase do?
activated by binding of the first messenger to receptor, leading to activation of G protein
catalytic site located on cytosolic surface of plasma membrane
catalyses conversion of cytosolic ATP to cyclic 3',5'-adenosine monophosphate
237
what is cAMP? what is it formed by?
cyclic 3',5'- adenosine monophosphate
adenylyl cyclase catalyses conversion of cytosolic ATP to cAMP
238
what does cAMP do?
acts as second messenger
239
how does ATP provide energy?
energy released when phosphate bonds are broken
input of energy needed to break bonds
as bonds reform in hydrolysis of ATP energy is released
energy released is greater than energy required to break bonds (weak)
240
what are the methods for generating ATP?
glycolysis, Kreb's cycle, oxidative phosphorylation, substrate level phosphorylation, ETC, beta oxidation
241
where does glycolysis take place?
cytosol
242
what is the overall reaction of glycolysis?
glucose + 2ADP +2NAD+ -> 2pyruvate + 4ATP + 2NADH + 2H+ + 2H2O
243
what is the simplified glycolysis equation?
glucose + 2ADP + 2Pi + 2NAD+ -> 2pyruvate + 2ATP + 2NADH + 2H+ + 2H2O
244
what is a kinase?
enzyme that adds/removes phosphate group to things from an ATP
245
what is an isomerase?
enzyme that rearranges structure of substrate without changing the molecular formula (similar to mutase)
246
what is an aldolase?
enzyme that creates or breaks carbon-carbon bonds
247
what is a dehydrogenase?
enzyme that moves hydride ion (H-) to an electron acceptor e.g. NAD+ or FAD+
248
what is an enolase?
enzyme that produces a carbon=carbon double bond by removing a hydroxyl group (OH)
249
NAD+/H+ in glycolysis
the NAD+ and H+ released in step 6 of glycolysis is used in the conversion of pyruvate to lactate which releases NAD+ that can be reused in step 6
250
when is pyruvate converted to lactate?
anaerobic conditions - cannot enter the Kreb's cycle or undergo oxidative phosphorylation (require oxygen
251
what is the reaction for pyruvate -> lactate
glucose + 2ADP + 2Pi -> 2lactate + 2ATP + 2H2O
252
what is the fate of lactate?
some of the lactate is released into the blood and taken up by heart and brain, then converted back to pyruvate and used for energy
taken up by liver as a precursor for formation of glucose, then released into blood
253
glycolysis in erythrocytes
contain all enzymes required but no mitochondria
anaerobic glycolysis
254
glycolysis in skeletal muscles
considerable amounts of glycolytic enzymes
few mitochondria
255
glycolysis in most cells
most don't have enough enzymes/glucose to rely on glycolysis alone
256
why is glycolysis inhibited in acidosis?
PFK-1 is pH dependent and inhibited by acidic conditions
257
what is PFK-1 inhibited by?
acidic conditions
258
what are regulators of glycolysis?
AMP, ATP
259
what effect does AMP have on glycolysis?
allosteric activator of PFK-1
binds to PFK-1 leading to conformational change - increasing affinity of PFK-1 for fructose-6-phosphate
260
what is an allosteric activator?
modifies the active site of the enzyme so the affinity for the substrate increases
261
what effect does ATP have on glycolysis?
allosteric inhibitor of PFK-1
low ATP levels = fast reaction speed of PFK-1 -> fructose-1,6-bisphosphate
high ATP levels = slow reaction speed of PFK-1 -> fructose-1,6-bisphosphate
262
AMP-ATP interaction
AMP opposes the allosteric inhibition by ATP
263
where does the Kreb's cycle take place?
mitochondrial matrix
264
what is the overall reaction in the Kreb's cycle?
acetyl CoA + 3NAD+ + FAD + GDP + ADP + Pi + 2H2O -> 2CO2 + CoA + 3NADH + 3H+ + FADH2 + GTP + ATP
265
what is the primary molecule entering the Kreb's cycle? where is it derived from? what is its function?
acetyl coenzyme A
B vitamin pantothenic acid
transfer acetyl groups (2 carbons) from one molecule to another
266
what can acetyl CoA be made from?
pyruvate, beta-oxidation of fatty acids or amino acid breakdown
267
requirements of Kreb's cycle
aerobic conditions - oxidative phosphorylation needed to convert NADH and FADH2 back to NAD+ and FAD
268
what are NAD+ and FAD used for?
conversion of isocitrate to a-Ketoglutarate and a-Ketoglutaate to succinyl CoA and succinate to fumarate and malate to oxaloacetate
269
mnemonic for Kreb's steps
can I keep selling socks for money officer?
```
Citrate
Isocitrate
a-Ketoglutarate
Succinyl CoA
Succinate
Fumarate
Malate
Oxaloacetate
```
270
mnemonic for Kreb's enzymes
so at another dance devon sipped down five drinks
```
citrate Synthetase
Aconitase
Aconitase
isocitrate Dehydrogenase
alpha-ketoglutarate Dehydrogenase
succinyl-CoA Synthetase
succinate Dehydrogenase
Fumarase
malate Dehydrogenase
```
271
glycolysis steps mnemonic
Girls Get Free Food
Guys Dine with Good Girls
Boys Pretend to Pay for the Pricy People
```
Glucose
Glucose 6 phosphate
Fructose 6 phosphate
Fructose 1,6 bisphosphate
Glyceraldehyde 4 phosphate and Dihydroxyacetone phosphate
G3P and G3P
1,3 Bisphosphoglycerate
3 Phosphoglycerate
2 Phosphoglycerate
Phosphoenolpyruvate
Pyruvic acid
```
272
glycolysis enzymes mnemonic
Hungry Peter Pan And The Growling Pink Panther Eat Pies
```
Hexokinase
Glucose-6-phosphate isomerase
Phosphofructokinase-1
Aldolase
Glyceraldehyde-3-phosphate dehydrogenase
Triosephosphate isomerase
Phosphoglycerate kinase
Phosphoglycerate mutase
Enolase
Pyruvate kinase
```
273
what are the conditions of beta oxidation?
strictly aerobic
dependent on oxygen, good blood supply and adequate numbers of mitochondria
274
what can acetyl CoA be derived from?
oxidation of fatty acids
must be activated in cytoplasm before being oxidised in the mitochondria
275
what is a fatty acid?
carboxylic acid group with many carbons attached
276
how are fatty acids activated?
in cytoplasm
fatty acid + ATP + CoA -> acyl CoA + PPi + AMP
adenosine taken away from ATP and used to make acyl-CoA
277
what is PPi?
pyrophosphate
278
where oxidation of fatty acids occur?
in mitochondria
most fatty acids that are over 12 carbons long, can't get through the outer-mitochondrial membrane on their own
279
what converts the acyl CoA? what does this now allow?
carnitine acyltransferase
acyl CoA -> acyl carnitine
acyl carnitine can now be transported into the mitochondria through outer membrane
280
where is carnitine acyltransferase 1 located?
outer mitochondrial membrane
281
what is the process of acyl CoA conversion?
Coenzyme A is removed from acyl CoA and is recycled
| carnitine is added
282
what happens to the acyl carnitine once inside the mitochondria?
carnitine acyltransferase 2 converts acyl carnitine back to acyl CoA
Coenzyme A is readded and carnitine ripped off
283
what is the carnitine shuttle?
carnitine can diffuse through outer mitochondrial membrane to be used again to convert acyl CoA to acyl carnitine
284
what is beta oxidation?
sequential removal of 2 carbon units by oxidation at the beta-carbon position of the fatty acyl-CoA
oxidation to carbonyl group
fatty acids are broken down to produce acetyl-CoA (krebs) and NADH and FADH2 (ETC)
285
what are the products of beta oxidation used for?
acetyl-CoA used in Krebs
NADH and FADH2 produced from beta oxidation and Krebs are used in oxidative phosphorylation
286
energy yielded from oxidation of fatty acids vs carbohydrates
significantly more energy per carbon
287
what is the net result of the oxidation of 1 mole of oleic acid vs 1 mole of glucose?
oleic acid is an 18-carbon fatty acid
145 moles of ATP vs 38
288
fatty acids as a fuel source in the nervous system
don't act as a fuel source as they can't get through the BBB
289
when are fatty acids used as fuel?
when hormones signal fasting or increased demand
290
examples of fatty acids
```
linoleic acid (18 carbons)
oleic acid (18 carbons)
palmitic acid (16 carbons
arachidonic acid (20 carbons)
```
291
where does oxidative phosphorylation occur?
inner mitochondrial membrane
292
what are the components of the ETC?
cytochromes (contain iron and copper cofactors, structure resembles iron haemoglobin) and associated proteins in inner mitochondrial membrane
293
what happens in the ETC?
2 electrons from hydrogen atoms are transferred from NADH, H+ or FADH2 to one of the proteins (oxidised)
electrons successively transferred to other compounds in redox reactions
electrons finally transferred to molecular oxygen, which combines with hydrogen ions to form water
294
where do hydrogen ions in the ETC come from?
free hydrogen ions and hydrogen bearing coenzymes (NADH and FADH2) that had been released earlier in ETC when electrons from hydrogen atoms were transferred to the cytochromes
295
as well as transferring the coenzyme hydrogens to water, what else does this process do?
regenerates hydrogen-free forms of coenzymes which can become available to accept 2 hydrogens from intermediates in krebs, glycolysis or beta oxidation
296
what does ETC provide?
aerobic mechanism for regenerating the hydrogen-free form of the coenzymes
297
energy released in the ETC. what is it used for? what does this create?
small amounts are released
as electrons are transferred, some is used by cytochromes to pump hydrogen ions from the matrix into the intermembranal space
source of potential energy - hydrogen-ion concentration gradient across membrane
298
what is embedded in the inner mitochondrial membrane?
enzymes - ATP synthase
299
where is ATP synthase found?
embedded in the inner mitochondrial membrane
300
what does ATP synthase do?
forms a channel in the membrane, allowing hydrogen ions to flow back into matrix via chemiosmosis
energy of the conc. gradient is converted into chemical bond energy by ATP synthase, which catalyses the formation of ATP from ADP and Pi
301
by what mechanism do the hydrogen ions move back into the matrix? what is this?
chemiosmosis - moving from an area of high conc of hydrogen ions to low conc
302
what does the transfer of electrons to oxygen produce?
2.5 and 1.5 molecules of ATP for each molecule of NADH and H+ and FADH2 respectively
303
what is the overall reaction for respiration?
C6H12O6 + 6O2 + 38ADP + 38 Pi -> 6CO2 + 6H2O + 34-38 ATP
304
how much ATP is produced from glycolysis?
34-38
38 is theoretical and assumes all of the NADH produced in glycolysis and krebs cycle enters into oxidative phosphorylation and all the free hydrogen ions are used in chemiosmosis for ATP
