Biochem Test 3 Metabolism

Front 1

What 4 pathways are available to the G6P branchpoint?

Back 1

1. Glycogen synt (phosphoglucomutase)
2. Pentose Phosph Pathway (HMP)
3. Glycolysis (glukokinase- high KM )
4. Gluconeogenesis (G6-Phosphatase)

Front 2

Reverse RXN of Pyruvate Kinase

Back 2

Pyruvate --> Oxaloacetate --> PEP
(pyruvate carboxylase + acetyl CoA, PEP Carboxykinase)

Front 3

How much glucose does 0.01 uM of glycogen equal?

Back 3

400 mM -> provides a great advantage of storing LOTS of glucose w/out osmolar signific.

Front 4

phosphoglucomutase

Back 4

Conversion of G1P --> G6P (glyogenolysis after glycogen phospohyrlase) or
G6P --> G1P (glycogenesis)

Front 5

What are the enzymes in glycogenolysis?

Back 5

1. Glycogen phosphorylase (G1P)
2. Phosphoglucomutase (G6P)
3. Glucose-6-Phosphatase (glucose + ppi)

4. Debranching enzyme (transglycosylase)
5. Glucosidase for a-1,6 linkage

Front 6

What is the second step in glycogen synthesis?

Back 6

Glucose activation: G1P --> UDP-Glucose
Enzyme: UDP-Glucose Pyrophosphorylase, adds PO4; subsequent PPi hydrolysis drives rxn forward
***Commitment step in glycogensis

Front 7

What happens to Activated Glucose (UDP-Glucose)?

Back 7

Glycogen synthase adds them to pre-existing glycogen chains at least 4 residues long. Prevents adding to free glucose.

Front 8

What is glycogenin and why is it important?

Back 8

An enzyme that has Tyr residues linked to glucose; it catalyzes addition of 7 more glu to itself, providing the substrate w/ >4 residues for Glycogen synthase.

Front 9

When is glycogen Synthase Active

Back 9

when it's NOT phosphorylated (insulin)
-Phosphorylated form inactive (glucagon, epinephrine)

Front 10

What are the states that Glycogen phosphorylase can exist in?

Back 10

T (inactive) vs. R (active)

b (inactive or unphosphorylated) vs. a (active, or phosphorylated)

Front 11

How is glycogen phosphorylase regulated differently in liver vs muscle

Back 11

-Skeletal muscle- senstive to energy charge (activated by AMP); inhibited by ATP and G6P; faster regulation need glucose in short term exercise
-Liver = phosphorylation controlled by hormones; stress

Front 12

What does Phosphorylase kinase do? What stimulates it?

Back 12

Phosphorylates Glycogen Phosphorylase; stim by Glucagon/Epi; inhibited by glucose/insulin

Front 13

Which storage disease is most common? What enzyme deficient?

Back 13

Von Gierke's - Glucose 6-Phosphatase

Front 14

Andersen Disease

Back 14

-Branching Enzyme (a-1,4 --> a-1,6)
-Effects liver and spleen
-Glycogen normal amount, but very long outer branches
-progressive cirrhosis of liver; liver failure causes death, usually before 2 years

Front 15

Hers Diease

Back 15

Phosphorylase in liver deficient
increased amt of glycogen in liver- live type 1 but milder

Front 16

Von Gierke's Diesase

Back 16

-Body doesn't kno can't make glucose, protien & AA keep mobilizing. Mass enlargment of liver; failure to thrive
-Severe hypoglycemia, ketosis, hyperuricemia, hyperlipemia

Hint 16

- see clinical features explanation other slide

Front 17

pyruvate kinase reaction

Back 17

PEP --> pyruvate

-deactivated by glucagon (PKA phosphorylates & deactivates), ATP, Alanine
-Activated by F-1,6 BP

Front 18

Fructose 2-6 Biphosphate

Back 18

High [F-2,6 BP] activates glycolysis (stimulates PFK-1) and inhibits F-1,6 BPtase )

Front 19

Fructuose 2-6 Biphospate Regulation -- low glucose

Back 19

Glucagon --> PKA --> phosphorylates PKF2 --> inhibits F-2,6 BP synth. Glycolysis inactive (PFK1), glucogenesis active (f-1,6 BPtase)

Front 20

Fructuse 2-6 BP regulation, high glucose

Back 20

High levels F6-P stimulate phosphoprotien phosphatase - PFK2 activated - glycolysis activated.

Front 21

Glucagon Cascade

Back 21

Low glucose --> adenlyl cyclase --> cAMP --> pKA -->
1) Active phosphorylase kinase --> phosphorylase + P (active) -- glyogenolysis,
2) Glycogen Synthase + P (inactive glycogen synth)
3) pyruvate kinase + P (inactive glycolysis)
4) PFK-2 + P (glycolysis inactive)
5) Active CREB - PEP carboxykinase gene expression

Front 22

how does insulin affect fatty acid synthesis

Back 22

activates (de-phoshorylates)
1) pyruvate dehydrogenase
2) acetyl CoA carboxylase (acetyl-CoA --> malanoyl CoA)

Front 23

First commitment step in FA synthesis

Back 23

Formation of malanoyl CoA from acetyl CoA (requires Biotin).
-stimulated by insulin, citrate (way actetyl CoA smuggled out to cytosol)
-inhibit by glucagon/epi, palmitoyl CoA (end product)

Front 24

Pyruvate Branch Points

Back 24

-Aerobic Oxidation (ac-CoA)
-Gluconeogensis (OAA)
-Lactate
-Alanine (AA synthesis)

Front 25

Malanoyl-CoA and regulation

Back 25

M-CoA synthesized from citrate as intermediate in FA synth. Inhibits carnatine shuttle (FA oxidation) so not synth. and degrading FA at same time

Front 26

Regulation of Pyruvate Carboxylase

Back 26

Pyruvate --> OAA

+glucagon (PKA activate CREB, + PEPCK gene expression). insulin - PEPCK gene expr
+ acetyl CoA

Front 27

FA synthase action

Back 27

Produces Palmitoyl CoA from acetyl CoA & maylonyl CoA (7 cycles); NADPH= source of reducing equivalents
-Methyl group of first actetyl CoA becomes methyl group of palmitate

Front 28

Elongation of FA

Back 28

-takes place in ER - similar to FA synthesis but use FA elongase
-Malanoyl CoA is 2C donor

Front 29

Insulin and Glucagon HmG reductase regulation

Back 29

-Insulin de-P enzyme (activates)
-glucagon/epi +P (inactivates)
via reductase kinase (RK). RK inactivated by +P via RKK. inactivation of inactivoar inhib by glucagon & epi by activating phosphoprotien phosphatase inhibior-1 (PPP1)

Front 30

HmG allosteric regulation

Back 30

When AMP levels high (ATP low) +P of HmG increased. HmG-P = inactive, so low ATP inhibits choles. synthesis

Front 31

G6P branch point - when does glycogen synthesis occur?

Back 31

High Km; Only operates at high [g-6-p]
-only when other pathway fully staruated do you build up G-1P

Front 32

Hexose monophosphate shunt

Back 32

glucose oxidized to CO2
-Remaining sugar intmed scarmbled through glycolyitic intm back to G6P - reoxidized. After 6 cycles - glucose carbons all oxidized to CO2 with production of 12 NADHPH

Front 33

If cell Fxn RNA/DNA synthesis (rapidly dividing cells)

Back 33

Don't need production of CO2 (stage 1)
F6P << Ribose-5-P (transaldolase)
Glyceraldehyde3P << Robse 5P by transkelotase

Front 34

Cell Fxn = biosynthesis, PPP rxn?

Back 34

Needs NADPH

Glucose oxidized to R5P

Front 35

Cell Fxn = general cell needs, PPP rxn?

Back 35

Oxidative and non-oxidative
-oxidize glucose to ribulose-5-P; isomerize ribulose 5-P to ribose 5-P

Front 36

Cell Fxn = biosynthetic pathways, PPP rxn?

Back 36

Cell needs NADPH, pyruvate, ATP
-pyruvate can be made from Glyceraldhyde 3-phosphate
-pyruvate can be convert to aetyl CoA and AA for biosynthesis

Front 37

Destruction of microorganisms with oxidative burst

Back 37

attachment of pathogen to phagocytic cell
2) ingestion of microorganism- form phagosome - phagosome can trigger formation of radical and H2O2 to break up bacterial cells
3) destruction of microoganism

Front 38

Need for NADPH in heme metabolism

Back 38

Heme - billverdin (via heme oxygenase)
Billverdin - Billrubin via Billverdin Reductase

Front 39

Synthesis of Nitric Oxide

Back 39

Arg + NADPH = hydroxyarginine
Hydroxy-arg + 1/2 NADPH = citrulline
NO (nitric Oxide)

Front 40

NO Fxn

Back 40

signal for blood vessel dialation (activates guanyly cyclase and cGMP production)
-macrophages produce high NO - combines with superoxide anion and produces OH and NO2 - extremly toxic