Glycogen & Glucose Metabolism

FSHN 3600

Regulation of Glycogenesis and Glycogenolysis

Glycogenesis occurs in a ___ state and glycogenolysis occurs in the ___ state.

fed, fasted

Regulation of Glycogenesis and Glycogenolysis

In the fasted state, ___ & ___ are the predominant hormones.

glucagon, epinephrine

Regulation of Glycogenesis and Glycogenolysis

____ is in the liver and ___ is in the muscle

glucokinase, hexokinase

Regulation of Glycogenesis and Glycogenolysis

Insulin binds to receptors on ___ cells to stimulate activity of ___.

liver, PP1

Regulation of Glycogenesis and Glycogenolysis

Glucokinase is ___ by insulin.

induced

Regulation of Glycogenesis and Glycogenolysis

(T/F) The Km for hexokinase is much lower than for glucokinase.

T

Regulation of Glycogenesis and Glycogenolysis

Hexokinase is allosterically inhibited by __-__-__.

glc-6-P

Regulation of Glycogenesis and Glycogenolysis

(T/F): Bother liver & muscle tissue express glc-6-P.

F

Muscle does not express glc-6-

Regulation of Glycogenesis and Glycogenolysis

Glycolysis occurs in the ___.

Cytosol

Regulation of Glycogenesis and Glycogenolysis

The hormone ___ regulates three glycolytic enzymes: GK, PFK, and PK.

insulin

Regulation of Glycogenesis and Glycogenolysis

Glycolysis is the process of oxidizing ___ to ___.

glucose, pyruvate

Regulation of Glycogenesis and Glycogenolysis

For every one glucose molecule, ___ pyruvate molecules are generated.

2

Regulation of Glycogenesis and Glycogenolysis

For each glucose molecule, there is a net production of molecules of NADH and __ molecules of ATP

2,2

Glycolysis

What do glucokinase (GK), Phosphofructokinase (PFK) and pyruvate kinase (PK) all have in common?

They’re unidirectional enzymes

Glycolysis

What is the substrate for GK?

glucose

Glycolysis

What is the substrate for PFK?

Fructose-6-P

Glycolysis

What is the substrate for PK?

Phosphoenol pyruvate (PEP)

Glycolysis

What is the product of GK?

Glc-6-P

Glycolysis

What is the product of PFK?

Fructose-1,6-biP

Glycolysis

What is the product of PK?

Pyruvate

What are example of allosteric regulation in glycolysis?

(+) High concentrations of ADP and NAD+ stimulate PFK

(-) High concentrations of NADH and ATP inhibit PFK

TCA Cycle

Which enzymes results in the production of CO2?

What reactions do these catalyze?

Pyruvate dehydrogenase (PDH) — Pyruvate + NAD+ —→ acetyl-CoA + CO2 + NADH

Isocitrate dehydrogenase (IDH) — Isocitrate + NAD+ —→ alpha-ketogluterate + CO2 + NADH

Alpha-ketoglutarate dehydrogenase (alpha-KGDH) — alpha-ketogluterate + NAD+ —→ Succinyl-CoA + CO2 + NADH

What are some examples of allosteric regulation that occur in the TCA cycle?

1. (+) High concentrations of ATP/ADP and NADH/NAD+ stimulate ___, ___, and __-__

2. (-) High concentrations of acetyl-CoA inhibit __

3. (-) High concentrations of citrate inhibit __.

1) PDH, IDH, alpha-KGDH

2) PDH

3) PFK

How many molecules of ATP do NADH and FADH2 yield?

1 FADH2 —→ 2 ATP

1 NADH —→ 3 ATP

Shuttle Systems

What are the two?

Hexose monophosphate shunt (HMS) and Malate-aspartate shuttle

Shuttle Systems

What is the purpose of HMS?

to generate a pentose (ribose) from a hexose to produce NADPH

Shuttle Systems

What is the mechanism of HMS?

NADP is reduced back to NADPH to support reductive process.

Shuttle Systems

What is the purpose of malate aspartate shuttle?

To allow NADH produced in the cytosol from glycolysis to enter the mitochondria to donate its electrons to the ETC.

Shuttle Systems

What is the mechanism of malate-aspartate shuttle?

NADH in the cytosol is oxidized to NAD+ and OAA is reduced to malate. Malate enters mitochondria and reverse reaction occurs. OAA cannot cross mitochondrial membrane so it’s transaminated to aspartate in mitochondria. Aspartate cross the mitochondrial membrane and is transaminated back to OAA in cytosol.

Shuttle Systems

What is the problem with HMS?

Needs NADPH for reductive anabolic reactions and ribose to form DNA/RNA.

Shuttle Systems

What is the problem with malate-aspartate shuttle?

NADH cannot cross the mitochondrial membrane.

What substrates can be used in gluconeogenesis?

NonCHO precursors such as amino acids, lactate, and glycerol.

Where does gluconeogenesis primarily occur?

Liver

Gluconeogenesis

What is pyruvate carboxylase’s substrate & product?

Substrate: pyruvate

Product: OAA

Gluconeogenesis

What is phosphoenolpyruvate’s (PEPCK) substrate & product?

Substrate: OAA

Product: PEP

Gluconeogenesis

What is fructose-1,6-biphosphatase’s substrate & product

Substrate: Fructose-1,6-biP

Product: Fructose-6-P

What is glucose-6-phosphatase’s substrate & product?

Substrate: Glc-6-P

Product: Glucose

An example of protein regulation in gluconeogenesis:

(+) Glucagon induces PC, PEPCK, fructose-1,6-biphosphatase, & glc-6-phosphatase

Hyperglycemia:

high circulating concentrations of glucose

Polyuria:

frequent urination

Polydipsia:

excessive thirst

Advanced glycation end products (AGEs):

prolonged high circulating glucose concentrations causing protein to become glycosylated (CHO added to protein)

Type 1 diabetes:

an autoimmune condition where the immune system destroys the beta cells of the pancreas, resulting in lack of insulin

Type 2 diabetes:

lack of cellular responsiveness to insulin

in muscle and adipose tissue, GLUT4 doesn’t translocate to the cell membrane

Resistant starch:

a broad category of dietary compounds that aren’t digested and absorbed

serves as energy source for gut microbiota

How can NADH cross into the mitochondrial membrane

Malate-aspartate shuttle