Sources of Gluconeogenesis Precursors
Glycogen branching cartoon
In exercising muscle, ____ also helps to activate phosphorylase kinase.
In exercising muscle, the elevated calcium (released to promote contraction) also helps to activate phosphorylase kinase.
Hepatomegaly usually indicates. . .
. . .defects in liver carbohydrate metabolism.
Regulation of glycogen phosphorylase
NAD+ and NADP+
Ketogenic-only amino acids
Leucine and Lysine. Thus they cannot be used to generate glucose.
Key Gluconeogenesis Steps
Why is glycogen stored as a polymer?
The high concentration of glucose 6-phosphate would create a strong osmotic load on the cell, causing water to enter and swell the cell, causing it to lyse
Glycogen molecular structure
Glycogen branching enzyme creates ____ linkages.
Glycogen branching enzyme creates α1→6 linkages.
Ratios of NAD+ to NADH and NADP+ to NADPH.
Akt in glycogen synthesis
Akt will also help stimulate glucose transport (Glut4)
Role of α1→6 glucosidases in glycogenolysis
α1→6 glucosidases remove the terminal α1→6 -bound glucose in a glycogen branch, leaving a linear chain.
Glycogenolysis and gluconeogenesis have the same _____.
Glycogenolysis and gluconeogenesis have the same terminal step.
This step is dephosphorylation by glucose-6-phosphatase, which produces free glucose that may be exported into the bloodstream.
UDP glucose synthesis
Glycogen synthase regulation
Akt is what phosphorylates GSK3, turning it off.
In order for glycogen synthase to add a glucose, the existing glycogen molecule must be ____.
In order for glycogen synthase to add a glucose, the existing glycogen molecule must be at least 4 glucose units long.
Thus the only storage forms of glucose in the body are. . .
1. Glycogen, which is used quickly
2. Amino acids, stored in muscle, which must be converted into glucose via gluconeogenesis
3. Glycerol, which is stored in triglycerides
What level of Acetyl-CoA would favor gluconeogenesis in the liver?
High acetyl CoA inhibits pyruvate dehydrogenase and activates pyruvate carboxylase, stimulating conversion of pyruvate to oxaloacetic acid.
Liver glycolysis vs gluconeogenesis diagram
When the body is fasting for prolonged periods, fats provide the major energy source for the body, but do not directly provide _____
When the body is fasting for prolonged periods, fats provide the major energy source for the body, but do not directly provide the carbon skeletons.
These are provided by amino acids.
Located in mitochondria
Where is PEP Carboxykinase located?
Where is pyruvate carboxylase located?
Pentose Phosphate Pathway from 10,000 ft
Glucose monomers are added and removed from the ____ ends of the polymer
Glucose monomers are added and removed from the “non-reducing” ends of the polymer
Why keep glucose-6-phosphatase in the ER?
1. It is not very specific, so it would interfere with other carbohydrate metabolism pathways
2. It is the same topology as the exterior, and it removes the G6P from the cytoplasm where it may exert inhibitory effects on the enzymes of glycogenolysis and gluconeogenesis.
Glycogen phosphorylase in Type IIb skeletal muscle
Type IIb muscle lacks the glucagon receptor and has very little insulin sensitivity.
Fates of Glucose-6-phosphate
Hepatocyte Glycogen Stores
Glycogen-containing granules appear black by SEM
Role of Pentose Phosphate Pathway in different tissues
Activity of glycogen branching enzyme
Phase I (Oxidate Phase) of Pentose Phosphate Pathway
Expressed only in liver, as only the liver needs export glucose from its glycogen stores.
NADPH feedback inhibition
Gluconeogenesis from 10,000 ft
G6P is an allosteric regulator of ___ and ___.
G6P is an allosteric regulator of glycogen synthase and glycogen phosphorylase.
Glycogen Phosphorylase Regulation in Muscle vs Liver
___ is the substrate used to make glycogen.
UDP-glucose is the substrate used to make glycogen.
This is because glucose must be chemically activated in order to be coupled to an elongating glycogen molecule.
Debranching of glycogen