Glucogenesis/lysis, gluconeogenesis, cori cycle

What is glycogenesis?

a process that converts excess glucose into glycogen in the liver and muscles

What is glycogen synthase stimulated by?

insulin

what is phosphorylase stimulated by?

glucagon (liver) and epinephrine (muscle)

What happens during glycogenesis?

After a meal, the pancreas releases insulin, which converts excess glucose to glycogen. Glucose molecules are added to the glycogenin chain by an a-1,4 bond, making the chain grow. When a growing chain reaches at least 11 glucose molecules, an enzyme transfers part of the chain to an a-1,6 bond

Key enzyme in glycogenesis

Glycogen synthase. Regulated by covalent modification (insulin)

Major storage sites of glycogen

Liver (100g)

Muscle (500g)

Galactose-1-phosphate uridyltransferase (GALT)

an enzyme catalyzing the second step of converting galactose to glucose. Deficiency of GALT causes galactosemia

Branching in glycogenesis

After a long chain of glucose molecules is produced (with a-1,4 bonds), branching enzymes add a glucose chain, about 7 units, to the growing chain, creating a-1,6 glycosidic bonds

What is glycogenolysis

A process to break down glycogen into individual glucose molecules in liver and muscle

What happens in glycogenolysis?

Either in fasting or exercising, glucagon or epinephrine is released and the terminal glucose from glycogen is hydrolyzed as glucose-1-phosphate by phosphorylase. G1P is rearranged to G6P by PG mutase.

How does glycogenolysis continue in the liver?

G6P converts to glucose by G6 phosphatase

How does glycogenolysis continue in the muslces?

G6P enters glycolysis due to lack of G6 phosphatase. Debranching enzyme hydrolyzes a-1,6 bond in the process.

Describe liver glycogen

• stimulated in fasting when BG decreases

• glucagon is secreted and glycogen breaks down to glucose

• glucose enters blood to raise BG to feed brain and RBC

Describe muscle glycogen

• stimulated when exercising

• Epinephrine is secreted

• glycogen breaks down to glucose

• glucose is used to fuel exercising muscle

• muscle does not have enzyme to turn G6P to glucose, so it flows to glycolysis

Gluconeogenesis

synthesis of glucose from non-CHO precursors to maintain blood glucose level in prolonged fasting or exercise

Non-CHO precursors used in gluconeogenesis

• lactate from muscle (cori cycle)

• amino acids from muscle protein (except leucine and lycine)

• glycerol from lypolysis

Lactate in gluconeogenesis

Produced with vigorous muscle exercise when oxygen is limited. It 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 in gluconeogenesis

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

Glycerol in gluconeogenesis

Released in adipocytes as a result of fat hydrolysis. Glycerokinase phosphorylates glycerol to glycerol-3-P which then converts to DHAP, entering gluconeogenesis

Gluconeogenesis is a unique pathway to the _______

liver. it does not happen in the muscle because of the lack of G6 phosphatase

Pyruvate carboxylase

reduces pyruvate to oxaloacetate and oxidizes ATP to ADP. requires biotin as a coenzyme

enzymes in step 1 of glycolysis

glycolytic: glucokinasen
gluconeogenic: G6 phosphatase

enzymes in step 3 of glycolysis

glycolytic: phosphorylase

gluconeogenic: fructose-1,6-biphosphotase

Enzymes in step 10 of glycolysis

glycolytic: pyruvate kinase

gluconeogenic: pyruvate carboxylase and PEP carboxylase

Importance of gluconeogenesis

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

• after 22 hours, 64% of glucose comes from gluconeogenesis

• after 42 hours, up to 80% of glucose from gluconeogenesis

How much of the glucose produced by the liver is used by the brain?

70%

Hexose monophosphate shunt

Pathway produces NADPH and Ribose 5-P that will be used in other biological reactions

Location of hexose monophosphate shunt

cytosol

Where is NADPH used?

Used for FA synthesis and other biosynthetic pathways

What is ribose-5-phosphate used for?

serves as foundation for DNA and RNA synthesis

Key enzyme in hexose monophosphate shunt

transketolase

3 parts of a nucleotide

phosphate group, pentose sugar, nitrogenous base