Lecture 6 Carbs

Question 1

D-glucose to L-lactate

Answer 1

2 ADP + phosphate –> 2 ATP. 10-11 steps. 6 carbons to 3 carbons.

Question 2

RBC blood amount

Answer 2

40% of blood, 3% total body mass, about 20g of glucose per day (10% body metabolism). 90% of glucose metabolized via glycolysis (lots of lactate).

Question 3

Key points of glycolysis to know

Answer 3

Know:
step 1: Glucose to Glucose-6-phosphate. Gives glucose - charge, prevents glucose from leaving cell easily. Know step product/reactant names.

Question 4

Glycogen

Answer 4

Stored Gluc-6-phos

Question 5

Glyceraldehyde-3-phosphate

Answer 5

Know this molecule.

Question 6

Pentose Phospha

Answer 6

precursor for forming DNA/RNA

Question 7

NADPH

Answer 7

Degrade/process drugs, antioxidant.

Question 8

Glucose

Answer 8

Break down for energy
Build up reserve energy (glycogen)
Build lipids
Build carbs for DNA/RNA
Produce NADPH (oxidative stress defense).

Question 9

Phosphofructo Kinase

Answer 9

PFK-1 - rate limiting enzyme for breaking glucose. fructose-6-P + ATP fructose-1,6-bisP + ADP. Highly regulated.

Question 10

GAPDH

Answer 10

Glyceraldehyde 3- phosphate dehydrogenase. Forms NADH+

Question 11

Phosphoglycerate Kinase

Answer 11

Takes phosphate group and adds it to ADP (first energy formation in glycolysis).

Question 12

Glycolysis location

Answer 12

Cytosol of cells - Glucose enters the Glycolysis pathway by conversion to glucose-6-phosphate.
Initially there is energy input corresponding to cleavage of two P bonds of ATP.

Question 13

Hexokinase

Answer 13

ATP binds to the enzyme as a complex with Mg++. Forms G-6-P

Question 14

Mg++

Answer 14

Mg++ interacts with negatively charged phosphate oxygen atoms, providing charge compensation & promoting a favorable conformation of ATP at the active site of the Hexokinase enzyme.

Question 15

Aldolase

Answer 15

Forms Glyceraldehyde 3 phosphate from fructose 1-6 bisphosphate. Aldol cleavage, reverse of aldol condensation.

Question 16

Phosphoglycerate Kinase

Answer 16

1,3-bisphosphoglycerate + ADP
3-phosphoglycerate + ATP
First ATP return.

Question 17

Pyruvate Kinase

Answer 17

PEP (phosphoenolpyruvate) +ADP –> pyruvate + ATP. Spontaneous transfer.

Question 18

Balance sheet for glycolysis

Answer 18

2 ATPs used, 4 ATP produced. 2 overall gained.

Question 19

Aerobic

Answer 19

Pyruvate fed into Krebs cycle (oxidized to CO2). NADH produced and used in electron transfer chain.

Question 20

Fermentation

Answer 20

Anaerobic orgs. Must reoxidize NADH, as NAD+ is required for GAPDH reaction. Reoxidized as pyruvate is converted to a more reduced compound. Skeletal muscles ferment, resulting lactate used in brain or heart for energy.

Question 21

Astrocytes

Answer 21

surround and protect neurons in the brain, ferment glucose to lactate and release it.

Question 22

Hexokinase inhibition

Answer 22

Inhibited by Glucose-6-phosphate

Question 23

PFK-1 inhibition

Answer 23

Inhibited by ATP, activated by AMP

Question 24

Pyruvate Kinase inhibition

Answer 24

Activated by Fructose 1-6 BP

Question 25

Build it up and break it to...

Answer 25

2x G3P. Precursor for yield stage. Know ATP using/generating enzymes.

Question 26

Pentose Phosphate Path

Answer 26

*6 to 5 carbon - base for DNA/RNA. In the process you generate NADPH* Later on you can reform molecule for G3P for glycolysis. Glucose 6 phosphate dehydrogenase oxidizes gluc-6-p to create NADPH. Important antioxidant molecule in body.

Question 27

NADPH

Answer 27

Important antioxidant. Forms fro G-6-P from G6PDH.

Question 28

GSH/GSSG Slide/relationship

Answer 28

Many oxidative species. Glutathione peroxidase takes the brunt of this, simultaneously reducing GSSG from GSH, where NADPH oxidizes this. **LOOK AT THIS SLIDE

Question 29

Glycogen

Answer 29

1300 calories stored, only 40 cal glucose on hand (used constantly). Glucose molecules linked together via alpha 1-4 glycosidic bonds. Can bifurcate to form branches. At branches you have alpha 1-6 links. UDP-glucose is the intermediate building block for glycogen.

Question 30

UDP-glucose

Answer 30

Building block intermediate for glycogen formation.

Question 31

UTP+glucose-1-phosphate

Answer 31

UDP-glucose

Question 32

Glycogenin

Answer 32

Link 1 UDP glucose to another glucose (lose UDP during this process. Initiates chain formation.

Question 33

Glycogen Synthase

Answer 33

Catalyzes elongation of glycogen chains initiated by glycogenin

Question 34

Where would you expect to find glycogenin in cell?

Answer 34

Most of the Glycogenin is found associated with glycogen particles (branched glycogen chains) in the cytoplasm.

Question 35

Reciprocal control

Answer 35

Both synthesis & breakdown of glycogen are spontaneous. If both pathways were active simultaneously in a cell, there would be a "futile cycle" with cleavage of one ~P bond per cycle (in forming UDP-glucose). To prevent such a futile cycle, Glycogen Synthase and Glycogen Phosphorylase are reciprocally regulated, by allosteric effectors and by phosphorylation.

Question 36

Glycogen phosphorylase

Answer 36

In muscle, subject to allosteric reg by AMP, ATP, G6P. Seperate isozyme of phosphorylase expressed in liver is less sensitive to these allosteric controls:  AMP (present significantly when ATP is depleted) activates Phosphorylase, promoting the relaxed conformation.  ATP & glucose-6-phosphate, which both have binding sites that overlap that of AMP, inhibit Phosphorylase, promoting the tense conformation.  Thus glycogen breakdown is inhibited when ATP and glucose-6-phosphate are plentiful. Break down by 1 glucose at a time.

Question 37

Glycogen Phosphorylase dimer

Answer 37

Homodimer - we have drugs that inhibit this enzyme. Why \would an inhibitor of glycogen phosphorylase be a suitable treatment for diabetes? Making breakdown of glucose harder, helping alleviate the large amount of glucose.

Question 38

Debranching enzyme

Answer 38

Takes branch away so you can break down more of glycogen molecule.

Question 39

From Glycogen

Answer 39

G1P to G6P - can be used in glycolysis or stripped of phosphate and put into blood. Similar in liver.

Question 40

Epinephrine

Answer 40

Increases glucose to blood.

Question 41

Glucagon pathway

Answer 41

Terminated quickly. G-protein can be destroyed or cAMP can be destroyed. Protein phosphatase activity can also be halted.

Question 42

Muscle vs. Liver glycogen

Answer 42

Liver glucose gets shipped out to other places. Muscle stays and is used immediately.

Question 43

Insulin

Answer 43

Too much glucose in blood. Absorb and build glucose to glycogen. Anabolic hormone. Anti-glucagon effects.

Question 44

Gluconeogenesis

Answer 44

Take breakdown material and form glucose. Not reversible at fructose 1-6- bisphosphatase step.

Question 45

Glycolysis and Gluconeogenesi9s

Answer 45

Reciprocally regulated. Local control - includes reciprocal allosteric regulation by adenine nucleotides.

Question 46

Local control

Answer 46

Phosphofructokinase (Glycolysis) is inhibited by ATP and stimulated by AMP.  Fructose-1,6-bisphosphatase (Gluconeogenesis) is inhibited by AMP.