MACRONUTRIENT BIOCHEMISTRY EXAM #4 - KENT STATE UNIVERSITY

Where does glycogenesis take place? Why?

liver (100g) and skeletal muscle (500g); liver utilizes stored glycogen for blood glucose regulation while skeletal muscle utilizes stored glycogen for exercise and local use in each muscle

Overview of the process of glycogenesis

After a meal, pancreas releases insulin, which converts excess glucose to glycogen; glucose molecules are added (alpha-1,4 bond) to glycogenin; when a growing chain reaches 11 glucose molecules, branching enzyme transfers a part of the chain (~6 glucose residues) to add alpha-1,6 bond to growing chains bonded by alpha-1,4 bonds

What is glycogen synthase?

an enzyme that joins together lots of chains of glucose molecules to make glycogen (a molecule used to store energy in animals); activated by insulin

What are the 5 steps of glycogenesis?

1. Glucose to G6P - glucose phosphorylation via hexokinase or glucokinase; this step can be reversed in the liver via *glucose-6-phosphatase* for glucose release into the blood

2. G6P to G1P - isomerization via phosphoglucomutase

3. G1P to UDPG - UTP and Glc-1P utilize G1P uridyltransferase AKA UDP-glucose pyrophosphorylase to become pyrophosphate and UDP-Glucose

4. Addition of glucose to glycogenin - UDP-glucose releases the glucose molecule onto the glycogenin structure releasing UDP attaching glucose and glycogenin (GS activation requires being stimulated by insulin to form glycogen)

5. Branching - repeated actions create long chains of glucose molecules (alpha-1,4 bonds); branching enzymes add a glucose chain (~7 units) to the growing chain creating alpha-1,6 glycosidic bonds

Step 1 of glycogenesis

1. Glucose to G6P - glucose phosphorylation via hexokinase or glucokinase; this step can be reversed in the liver via *glucose-6-phosphatase* for glucose release into the blood

Step 2 of glycogenesis

2. G6P to G1P - isomerization via phosphoglucomutase

Step 3 of glycogenesis

3. G1P to UDPG - UTP and Glc-1P utilize G1P uridyltransferase AKA UDP-glucose pyrophosphorylase to become pyrophosphate and UDP-Glucose

Step 4 of glycogenesis

4. Addition of glucose to glycogenin - UDP-glucose releases the glucose molecule onto the glycogenin structure releasing UDP attaching glucose and glycogenin (GS activation requires being stimulated by insulin to form glycogen)

Step 5 of glycogenesis

5. Branching - repeated actions create long chains of glucose molecules (alpha-1,4 bonds); branching enzymes add a glucose chain (~7 units) to the growing chain creating alpha-1,6 glycosidic bonds

What is glycogenin?

An enzyme that autoglucosylates (7) to form a primer for glycogen​

What is happening to glycolysis and glycogenesis when fasting?

Both processes slow down due to lack of available glucose and G6P

What is the process of glycogenolysis in the liver?

Glycogen phosphorylase cleaves a glucose molecule and utilizes an inorganic phosphate to release a single molecule of glucose from glycogen creating Glucose-1-phosphate; glucose-1-phosphate is then isomerized to glucose-6-phosphate by phosphoglucomutase and later dephosphorylated by Glucose-6-phosphatase becoming glucose before being released into the blood

What is the process of glycogenolysis in the muscle?

Glycogen phosphorylase cleaves a glucose molecule and utilizes an inorganic phosphate to release a single molecule of glucose from glycogen creating Glucose-1-phosphate; glucose-1-phosphate is then isomerized to glucose-6-phosphate by phosphoglucomutase. G6P is then sent off through glycolysis and the TCA cycle to release energy and be utilized by the muscles

Glycogenolysis in the liver summary

Stimulated in fasting ​

BG goes down and pancreas secretes *glucagon* to initiate glycogenolysis

Glucose molecules enter blood to raise BG (brain & RBC)

Glycogenolysis in the muscle summary

Stimulated when exercising ​

The hormone *epinephrine* is released to initiate glycogenolysis

Glucose molecules are not released into circulation but used to fuel exercising muscle (local use)

Muscle does not have enzyme that converts G6P to glucose (G6P phosphatase), so G6P flows down to glycolysis.

What is gluconeogenesis? Details.

Synthesis of glucose from non-carbohydrate precursors (Lactate, AAs except leucine and lysine, and glycerol)

Reversal of glycolysis except at 3 irreversible steps which are bypassed by 4 gluconeogenic enzymes

What are the gluconeogenic enzymes and in which steps are they used?

11. Glucose-6-phosphatase (reverses the 1st step of glycolysis)

9. Fructose-1,6-bisphosphatase. (Reverses the 3rd step of glycolysis)

2. Pyruvate carboxylase (1/2 enzyme reversing 10th step of glycolysis)

3. PEP carboxykinase (2/2 enzyme reversing 10th step of glycolysis)

Lactate from muscle (Cori Cycle) conversion in gluconeogenesis

Lactate is produced during vigorous muscle stimulating exercise when O2 is limited

Lactate then goes out to the blood and converts to pyruvate entering gluconeogenesis in the liver

Regenerated glucose enters into blood and then to muscle (cori cycle)

Amino Acids from muscle protein conversion in gluconeogenesis

After deamination, carbon skeletons form pyruvate or TCA cycle intermediates entering gluconeogenesis

Glycerol from lipolysis conversion in gluconeogenesis

Glycerol is released in adipocytes as a result of fat hydrolysis

Glycerokinase phosphorylates glycerol to glycerol 3-Phosphate which then, converts to DHAP via glycerol-3P DH entering gluconeogenesis​

What is the importance of gluconeogenesis?

Brain uses 70% of the total glucose produced by the liver in fasting

During the first hours of fasting, glycogenolysis is the primary source of glucose

After several hours of starvation, gluconeogenesis and glycogenolysis contribute equally to blood glucose

After 14 hr starvation, about 54% of glucose comes from gluconeogenesis, and this contribution raises to 64% after 22 hours and up to 84% after 42 hours​

When does gluconeogenesis occur?

during periods of prolonged fasting/starvation and vigorous exercise

Where does glucose synthesis take place?

Liver, sometimes small amount in kidney​

During the first 18 to 24 hours of a fast, the vast majority of gluconeogenesis occurs in the liver. In prolonged fasting, kidney participation in gluconeogenesis is increased and is responsible for about 40% of total gluconeogenesis

What is the hexose monophosphate shunt?

Also is called Pentose Phosphate Pathway (PPP)​

Location: cytosol​

This pathway produces NADPH and Ribose 5-P that will be used in other biological reactions​

NADPH* is used for fatty acid synthesis and other biosynthetic pathways​

Ribose 5-phosphate* serves as foundation for DNA and RNA synthesis

What is the Cori Cycle? Where does Cori Cycle metabolism occur?

A process in the liver that regenerates glucose from lactate released by muscles

ATP consumption and production throughout Cori Cycle?

Glucose --> 2 Pyruvate --> 2 Lactate = 2 ATP

2 Lactate --> 2 Pyruvate --> Glucose = -6 ATP equivalents (-4 ATP & -2 GTP)

What is the purpose of the Cori Cycle?

To remove lactate from the muscle and transport it to the liver where it can undergo gluconeogenesis

What is NADPH used for?

fatty acid synthesis and other biosynthetic pathways​

What is Ribose-5-phosphate used for?

foundation for DNA and RNA synthesis