Lecture 6 Carbs Flashcards
D-glucose to L-lactate
2 ADP + phosphate –> 2 ATP. 10-11 steps. 6 carbons to 3 carbons.
RBC blood amount
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).
Key points of glycolysis to know
Know:
step 1: Glucose to Glucose-6-phosphate. Gives glucose - charge, prevents glucose from leaving cell easily. Know step product/reactant names.
Glycogen
Stored Gluc-6-phos
Glyceraldehyde-3-phosphate
Know this molecule.
Pentose Phospha
precursor for forming DNA/RNA
NADPH
Degrade/process drugs, antioxidant.
Glucose
Break down for energy Build up reserve energy (glycogen) Build lipids Build carbs for DNA/RNA Produce NADPH (oxidative stress defense).
Phosphofructo Kinase
PFK-1 - rate limiting enzyme for breaking glucose. fructose-6-P + ATP fructose-1,6-bisP + ADP. Highly regulated.
GAPDH
Glyceraldehyde 3- phosphate dehydrogenase. Forms NADH+
Phosphoglycerate Kinase
Takes phosphate group and adds it to ADP (first energy formation in glycolysis).
Glycolysis location
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.
Hexokinase
ATP binds to the enzyme as a complex with Mg++. Forms G-6-P
Mg++
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.
Aldolase
Forms Glyceraldehyde 3 phosphate from fructose 1-6 bisphosphate. Aldol cleavage, reverse of aldol condensation.
Phosphoglycerate Kinase
1,3-bisphosphoglycerate + ADP
3-phosphoglycerate + ATP
First ATP return.
Pyruvate Kinase
PEP (phosphoenolpyruvate) +ADP –> pyruvate + ATP. Spontaneous transfer.
Balance sheet for glycolysis
2 ATPs used, 4 ATP produced. 2 overall gained.
Aerobic
Pyruvate fed into Krebs cycle (oxidized to CO2). NADH produced and used in electron transfer chain.
Fermentation
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.
Astrocytes
surround and protect neurons in the brain, ferment glucose to lactate and release it.
Hexokinase inhibition
Inhibited by Glucose-6-phosphate
PFK-1 inhibition
Inhibited by ATP, activated by AMP
Pyruvate Kinase inhibition
Activated by Fructose 1-6 BP
Build it up and break it to…
2x G3P. Precursor for yield stage. Know ATP using/generating enzymes.
Pentose Phosphate Path
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.
NADPH
Important antioxidant. Forms fro G-6-P from G6PDH.
GSH/GSSG Slide/relationship
Many oxidative species. Glutathione peroxidase takes the brunt of this, simultaneously reducing GSSG from GSH, where NADPH oxidizes this. **LOOK AT THIS SLIDE
Glycogen
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.
UDP-glucose
Building block intermediate for glycogen formation.
UTP+glucose-1-phosphate
UDP-glucose
Glycogenin
Link 1 UDP glucose to another glucose (lose UDP during this process. Initiates chain formation.
Glycogen Synthase
Catalyzes elongation of glycogen chains initiated by glycogenin
Where would you expect to find glycogenin in cell?
Most of the Glycogenin is found associated with glycogen particles (branched glycogen chains) in the cytoplasm.
Reciprocal control
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.
Glycogen phosphorylase
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.
Glycogen Phosphorylase dimer
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.
Debranching enzyme
Takes branch away so you can break down more of glycogen molecule.
From Glycogen
G1P to G6P - can be used in glycolysis or stripped of phosphate and put into blood. Similar in liver.
Epinephrine
Increases glucose to blood.
Glucagon pathway
Terminated quickly. G-protein can be destroyed or cAMP can be destroyed. Protein phosphatase activity can also be halted.
Muscle vs. Liver glycogen
Liver glucose gets shipped out to other places. Muscle stays and is used immediately.
Insulin
Too much glucose in blood. Absorb and build glucose to glycogen. Anabolic hormone. Anti-glucagon effects.
Gluconeogenesis
Take breakdown material and form glucose. Not reversible at fructose 1-6- bisphosphatase step.
Glycolysis and Gluconeogenesi9s
Reciprocally regulated. Local control - includes reciprocal allosteric regulation by adenine nucleotides.
Local control
Phosphofructokinase (Glycolysis) is inhibited by ATP
and stimulated by AMP.
Fructose-1,6-bisphosphatase (Gluconeogenesis) is
inhibited by AMP.
