Enzyme Nomanclature. CP and ATP Use During Exercise Myokinase reaction 2 ADP ATP + AMP.
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Transcript of Enzyme Nomanclature. CP and ATP Use During Exercise Myokinase reaction 2 ADP ATP + AMP.
Enzyme Nomanclature
H - C - H
-H
C - C - C
- OH
C - C = O
-H
C - C = O-C
C - C = O
-OH
O = C = O
methyl
alcohol
aldehyde
keto
carboxylic acid
Carbon dioxide
Glycolysis
Glycolysis-conversion of glucose to pyruvate,
ATP & NADH + H+
O
C P
Glucose-6-P
O
C
(C6H12O6)
Glucose
ATP ADP
- IRREVERSIBLE (kinase reaction)--Glucokinase in liver, Hexokinase in skeletal muscle
- takes 1 ATP
- now locked in cell because phosphorylated compounds can’t cross cell membranes by diffusion and are not recognized by GLUT transporters
- Keeps intracellular free glucose levels very low to maintain facilitated diffusion gradient
Glycolysis (cont.)
Step 2:
O
C POC CP
Glucose-6-P Fructose-6-PG-6-P Isomerase
Isomerization (rearrangement of bonds)
-(ie Aldose Ketose)
-frees the #1-C to be phosphorylated
Step 3:
OC CP
(Phosphofructokinase (PFK)-1)
Fructose-6-P Fructose-1,6-Bisphosphate
Irreversible (kinase reaction)
- takes 1 ATP (-2 so far)
- phosphorylates fructose at 1-C
Glycolysis (cont.)
OC CP PATP ADP
Glycolysis (cont.)
Step 4:
H
CCC
CCC
H
H
HHH
H
O
HOO
P
O POHOH
H
C
C
H OOC
HO H
H
PCC
H
HH
OOH
P
COH
+
DHAP G-3-P
DHAP= dihydroxyacetone phosphate (3-C)
G-3-P= Glyceraldehyde 3 phosphate (3-C)
(aldolase)
F-1,6 BP (6-C)
Glycolysis (cont.)Step 5:
CCC OH
OO
P
Triose - P Isomerase
C O P
H OHC
COH
DHAP G-3-P
Isomerization - rearrangement of Bonds
- Ketose Aldehyde
- 1 G-6-P 2 G-3-P
Glycolysis (cont.)Step 6:
No Energy has been gained YET! -2 ATP
C
C O
OH
COH
P
1, 3, D.P.G
C
C O
OH
CO O
P
P
G-3-P
NAD+ NADH + H+
Pi
-Phosphoglyceraldehyde dehydrogenase
-NAD+ reduced
-Aldehyde C oxidized to carboxylic acid
Glycolysis (cont.)Step 7:
1, 3, DPG
C
C O
OH
C
P
OO P
(2x) C
C O
OH
C
P
O-O
3 Phosphoglycerate
ADP ATP
(Phosphoglycerate kinase)
*1, 3 DPG has a G of -11.8 (ATP = -7.3)
Substrate level phosphorylation
Glycolysis (cont.)
Step 8:
C
C O
OH
C
P
O-O
3 Phosphoglycerate
C
C OHO
C
P
O-O
(Phosphoglycerate mutase)
2 Phosphoglycerate
*mutase - transfers a phosphate group
Glycolysis (cont.)
Step 9:
C
C OH
O
C
P
O-O
2 Phosphoglycerate
(Enolase) C
C
O
C
P
O-O+H20
Phosphoenol pyruvate (PEP)
This is a dehydration step. WHY?
G of PEP = - 14.8
Glycolysis (cont.)
Step 10:
C
C
O
C
P
O-O+H20
PEP
ADP ATP
(Pyruvate kinase)C O
CO-O
CH3
Pyruvate
Generate 2 ATP via substrate level phosphorylation
Glycolysis (cont.)
Step 11:
C
CH3
O
CO-O
Pyruvate
NADH + H NAD
(Lactate Dehydrogenase)
C O
CO-O
CH3
Lactate
NADH + H oxidized to NAD
pyruvate reduced to lactate
H H
step 6
LDH Isozymes
LDH-H has a high Km for pyruvate (lactate to pyruvate)
LDH-M has a low Km for pyruvate (pyruvate to lactate)
Glycolysis - Summary
Step 1: - 1 ATP
Step 3: - 1 ATP
Step 6: + 2 NADH + H +
Step 7: + 2 ATP phoshoglyceraldehyde kinase
Step 10: + 2 ATP pyruvate kinase
+ 2 ATP via substrate-level phosphorylationNET
Key regulated enzymes: PFK and HK
Key enzyme: PFK (step 3)
-allosterically regulated
Glycolysis - Summary (cont.)
Activated by:
- AMP, ADP, PI
Inactivated by:
- ATP
- Citrate
- H+
CP and ATP Use During Exercise
Myokinase reaction 2 ADP ATP + AMP
Glycolytic Flux with Graded Exercise
Over rest: 7.5x 39.5x 65x 323x
Over 35% VO2 max ---- 5.2x 8.6x 43x
Cell to Cell Lactate Shuttle
Immunolabeling of LDH using antibodies conjugated with 15nm
gold particles
Monocarboxylic transporterMCT 1-8
mMCTpmMCT
The matrix contains Pyruvate Dehydrogenase, enzymes of Krebs Cycle, and other pathways, e.g., fatty acid oxidation & amino acid metabolism.
matrix
inner membrane
outer membrane
inter- membrane
space
mitochondrion
cristae
Localization of Krebs Cycle: Glycolysis occurs in the cytosol of cells.
Pyruvate transported into the
mitochondrion to be metabolized further.
Mitochondrial Compartments:
Inner membrane infoldings, called cristae, contain constituents of the respiratory chain & ATP Synthase.
The inner membrane is the major permeability barrier.
It contains various transport catalysts, including a carrier protein that allows pyruvate to enter the matrix.
Mitochondrial compartments
matrix
inner membrane
outer membrane
inter- membrane
space
mitochondrion
cristae
Pyruvate Dehydrogenase, catalyzes oxidative decarboxylation of pyruvate, to form acetyl-CoA.
H 3 C C C O
O O
C S
O
H 3 C Co A
HSCo A
N A D + N A D H
+ C O 2
P y r u v a t e D e h y d r o g e n a s e
p y r u v a t e a c e t y l - C o A
Pyruvate Dehydrogenase is a large complex, with multiple copies of each of 3 enzymes:E1, E2 & E3.
Acetyl CoA, a product of the Pyruvate Dehydrogenase reaction, is a central compound in metabolism.
a c e t y l - c o e n z y m e A
H 3 C C
O
S C o A
View an animation of the Pyruvate Dehydrogenase reaction sequence.
Activation of PDH with Graded Exercise
Regulation of PDH during exercise
*
% of CHO from:
Glycogen 74% 91% 93% 99%
Blood glucose 26% 9% 7% 1%
% of pyruvate into:
CAC 100% 34% 26% 7%
HLA 0% 66% 74% 93%