METABOLIC BIOCHEMISTRY Summer 2006 Lecture 6 August 18, 2006.
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Transcript of METABOLIC BIOCHEMISTRY Summer 2006 Lecture 6 August 18, 2006.
METABOLIC BIOCHEMISTRY
Summer 2006
Lecture 6
August 18, 2006
RECAPITULATION
• GLYCOGEN BREAKDOWN
• GLYCOGEN SYNTHESIS
Figure 15-4
Pyridoxal phosphatecofactor
1234
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1
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Figure 15-4
Figure 15-4
Hydrolysis, NOTPhosphorolysis
Figure 15-10
Start with glycogenin, a primer and enzyme.
Muscle form and Liver form (glycogenin-2)
+
UDP-glucose
Figure 15-11a
INITIATION
LNC (3rd ed) 20-14(not found in 4th edition)
Figure 15-8
ELONGATION
Figure 15-9
Figure 15-11b
Each molecule has one glycogenin at the reducing end, and many non-reducingends from which degradation can start
CONTROL OF GLYCOGEN SYNTHESIS
AND
BREAKDOWN
Fig 15-13
phosphorylasesynthase
Phosphofructokinase (PFK-1)
Fructose-1,6-bisphosphatase
GLYCOGEN
UDP-Glu Glu-1P
Glu-6P
Fru-6P
Fru-1,6 bis P
DHAP + GAP Four key enzymes controlling thefate of carbohydrate/glucose in ourtissues
Fig 15-14
Fig 15-24
Fig 15-26
Covalent modifications
Ligand-inducedconformational changes
ATP cAMP
adenylcyclase
phosphodiesterase
AMPADP
GTP cGMP
guanylcyclase
phosphodiesterase
LNC 12-15
hormone
Glycogen ==> Glu-1-P
Fig 15-25
Fig 15-27
Fig 15-29
S T U V W
HORMONE
A
B
C
D
E
F
M N O P Q RE6
E5
E1 E2 E3 E4
Three pathways controlled by a single hormone
A signal transduction pathway
LNC Chapter 16
The Citric Acid Cycle
Krebs CycleTCA Cycle
From G. Perkins, C. Renken, M.E. Martone,S.J. Young, M. Ellisman, and T. Frey
Outer membraneInner membrane
Intermembrane spaceMatrix
Pyruvate dehydrogenase as seen by electronmicroscopy
E. coli enzyme:
Mass > 4.5x106
24 copies of transacetylase (E2)
24 copies of pyruvate dehydrogenase (E1)
12 copies of dihydro-lipoyl dehydrogenase
Pyruvate + CoASH + NAD+ acetyl-CoA + CO2 + NADH
E1
E3E2
The enzyme requires five co-factors:Coenzyme A
Thiamine pyrophosphate (TPP)Lipoic acid
FADNAD+
LNC 16.3
Coenzyme A
LNC 16.14
Lipoamide
LNC Fig. 13-18
FAD/FMN
FADH2/FMNH2
Figure from previous edition of LNC
Fig. 16.6
TCA CYCLEKrebs cycleCitric acid
cycle
LNC 16.11
Products from one turn of the Krebs cycle
C4
C4
C4
C4
C6
C2
C5
C4
C6
LNC 16.8
Citrate Synthase
open form without substrates
closed from with substrates bound
oxaloacetate: yellowacetyl-coA: red
LNC 16.9 Iron-sulfur center in aconitase
X
Stereospecificity of the aconitase reaction
with citrate
LNC 16.14
LNC Fig.16.7
the only membrane-bound enzyme in the TCA cycle
LNC Fig.16.18
regulatory molecules:
NADHATP, ADPCa+2
key allosteric enzymes:
the dehydrogenasescitrate synthase
LNC Fig.16.15 the Krebs cycle is amphibolic
THE GLYOXYLATE CYCLE
LNC Chapter 16, pages 623-626
LNC Fig.16-20 Note that the figure 16-16 in the 3rd edition has an error(there is an O instead of an H)
C6
C6
C4
C4
C4C2C2
C2
from oxidation of fatty acids
LNC Fig.16.22
End of lecture 6August 18, 2006