METABOLIC BIOCHEMISTRY

Summer 2006

Lecture 6

August 18, 2006

RECAPITULATION

• GLYCOGEN BREAKDOWN

• GLYCOGEN SYNTHESIS

Figure 15-4

Pyridoxal phosphatecofactor

1234

1234

1234

1234

1

1234234

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