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Human Gene expression
Expressing a gene
RNA polymerase binds to promoter, p
region, ONLY when effector binds to
enhancer element region of DNA
RNA polymerase adds nucleotides to
growing RNA polymer according to
base sequence in DNA sense strand.
ee
p
gene
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________________________________DNA_
p
gene
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RNA
RNA polymerase
RNA STAND
RNA polymerase
DNA STRAND
Compare codes and products
OH
5’P
end
O
RNA SYNTHESIS
-decodes DNA
O
OH
O
OH
growing
O
RNA strand
DNA
template
O
Master audio tape
Gene/DNA
Code is pattern of
metal oxide on tape
Code is sequence
nucleotides.
Cassette tape
decodes Master.
RNA decodes DNA.
Product is sound.
Product is protein
OH
RNA pol :O H
enzyme
O
OH
OH
Decoding the Master tape
(mRNA is decoded on ribosomes)
Master
tape
DNA
RNA
cassette tape
Tape player decodes cassette tape
Code is transferred
to cassette tape.
Tape must be
perfectly
packaged to
produce
the product,
Sound .
Gene Expression
Gene Expression
Enzymes form RNA from sequence
of nucleotides in tiny region
of DNA, passing on the code to
be decoded on the ribosomes.
RNA polymerase adds nucleotides to
growing RNA polymer according to
base sequence in DNA sense strand.
p
gene
__________________________________
_________________________________
RNA
RNA polymerase
Modification of mRNA
mRNA
mRNA
tail
cap
cap
tail
cap (me G) and poly A tail are added to
protect mRNA from cellular enzymes
that would degrade it
ribosome
mRNA moves through
ribosome
M
A
mRNA
M
tRNA-adapter
amino acid
Decoding mRNA
(translation)
A
peptide bond forms
Translation of mRNA
mRNA
A
M
mRNA
tail
A
M
Translation
of mRNA
tRNAM leaves
S
mRNA is moving through ribosome
as protein is forming
Translation of mRNA
mRNA
G
C
mRNA
V
L
V
mRNA is moving
throughribosome
as protein forms
S
A
G
protein is formed
C
S
M
mRNA
L
STOP codon
at end of
mRNA halts
protein
formation
stop codon
protein is formed
G
C
S
S
A
A 1 M
M
A
M
1
stop codon
newly-made protein
must be modified
before it becomes
active
H
V
H
H
A
M
Modifications to
newly-made proteins
1. Remove signal sequence
(often at N-terminal end of protein)
2. Add acetyl group to new N-terminal
Remove signal sequence
met-ala-ser-cys-val-ile-tyr-phe-ala-pheNH3
Signal sequence directs
newly-made protein to correct
location in cell.
3. Add -OH groups to pro or lys
Signal sequence is removed by
proteases when protein
reaches cellular destination.
4. Add glucose to asn or other a.a. units
Add acetyl group to
new N-terminal
glycogen
glu
glu
f-6-P
ala-phe-his-glu-asn-gln-pro--------NH
C=O
CH3
- acetyl group prevents cellular
proteases from degrading
protein too rapidly
Normal levels of blood glucose
range from 90 - 110 mg / 100 ml.
As glucose levels fall below 90 mg/dl,
glucagon is secreted and binds to
liver cells; glycogen is degraded
and blood glucose levels rise.
gly.P
f-1,6-diP
3-PG
OAA
PEP
malate
malate
Blood glucose levels
g-6-P
DHAP
pyr
pyr
OAA
gly.P
pyr
malate
DHAP
acetyl Co A
citrate
OAA
succinate
succ.CoA
isocitrate
G
Pasteur Effect
Glucose consumption and lactate
formation decrease when cells
use much more oxygen.
Explain the molecular basis for this.
in cells
with
low oxygen
glycogen
glu
glu
g-6-P
glu
g-6-P
f-6-P
f-6-P
f-1,6-diP
3-PG
OAA
PEP
cells with
high oxygen
glycogen
glu
DHAP
gly.P
NAD:H
pyr
lactate
malate
gly.P
f-1,6-diP
NAD:H
3-PG DHAP gly.P
OAA
PEP
malate
malate
pyr
pyr
OAA
pyr
malate
DHAP
acetyl Co A
citrate
OAA
succinate
succ.CoA
isocitrate
G
Molecular basis
for Pasteur Effect
Molecular basis for
Pasteur Effect
- when O::O usage increases, much
more ATP is formed since
TCA cycle and ETS operate
- as cells increase use of O=O,
cytoplasmic NAD+ is regenerated
through -glycerol P shuttle
- increased [ATP] inhibits pfk and rate
of glycolysis decreases, lowering
glucose consumption
- thus the rate of lactate formation
is decreased
Oxygen debt
When severe exercise ends, the
increased rate of respiration
(O=O consumption) continues
for several minutes.
Increased intake of O=O is required to
accept electrons still in ETS.
Energy requirements for
marathons
Approximately 100 Kcal/mile for
26 + miles are expended,
regardless of the pace.
- 2600 Kcal is required;
more if temp. is over about 65°F
Fuel reserves
fuel
tissue
amt./ave. man*
glucose
blood
40 Kcal
glycogen
liver
muscle
200 Kcal
400 Kcal
triglycerides adipose
100,000 Kcal
protein
muscle
25,000 Kcal
Use of fuels
heart
fatty acids used to form
ATP for muscle contaction
skeletal muscle
fatty acids and some glucose used
to form ATP for muscle contaction
brain
absolute requirement for glucose
* ave. 155 lb. man
Fuel Utilization in marathon
possible
actual
fuel sources miles miles to depletion
glucose
in blood
0.5
2-3
glycogen
liver
2.0
4.0
11
20 - 26
fatty acids
many
26 +++
protein
not available for energy
muscle
Skeletal muscle fibers
% fiber type
ave. Olympic Olympic
quadriceps
man sprinter marathoner
Type I (aerobic)
58
30
80
Type II (anaerobic) 42
70
20
% fiber content is genetically determined .
[glycogen] is same for both fiber types.
Muscle fibers
Skeletal muscles are composed of
2 types of fibers:
Type I
red fibers (aerobic,oxidative)
-used for prolonged work
Type II
white (anaerobic)
-used for high intensity work
of short duration
Endurance training
1. induces proliferation of
mitochondria in Type I fibers
2. increases %Type IIa fibers
(have some oxidative capacity)
3. increases capacity of body to
mobilize fuels (fatty acids,glucose)
by increasing vascular system
Hormonal control of
blood glucose
- normal [ glucose ] in blood
varies from 80 - 120 mg/100 ml
- brain requires [ glucose]
above 90 mg/100ml for
maximal function
Hormonal control of
blood glucose
Liver cells
-glucagon binds to receptor protein in
liver cell membrane resulting in
increased cAMP formation,
breakdown of glycogen
and release of glucose into blood
Glycogen depletion
Fuels used
blood glucose
glucose from liver glycogen
g-6-P from muscle glycogen
fatty acids from fat cell trigly
skeltal muscle
glycogen depletion
mile #
1-3?
3-18?
11-?
2-26+
exhaustion
Hormonal control of
blood glucose
Skeletal muscle
- insulin binds to skeletal muscle
receptor protein causing increased
cAMP formation and stimulation of
glucose transport into muscle cells
- decreases blood [glucose] dramatically
Hormonal control of
fuel reserves
Adipose cells
- glucagon binds to receptor protein
in adipose cell membrane
stimulating cAMP formation,
accelerating breakdown of:
triglycerides
fatty acids + glycerol
Glycogen loading
- to do “glycogen loading”, the runner
must deplete the glycogen stores
by running 20 miles, several
days before the event
-then eating a diet high in CHO’s
for several days replaces the
glycogen and adds as much as
30% more