Carbohydrate Metabolism I

Question 1

Glucose and glycogen

Answer 1

Constant supply of glucose is required by glucose dependent tissues (brain and RBC);
Dietary glucose is intermittent;
Glucose is highly soluble and osmotically active - cannot be stored;
Glucose is stored as a polymer - glycogen;
Major glycogen stores in skeletal muscle and liver;
Muscle glycogen is used by the tissue itself;
Liver glycogen is used to maintain blood glucose conc (homeostasis);

Question 2

Percentage of skeletal muscle and liver that is glycogen;
Glycogen is made in which state?;
Glycogen reserves last?
Glycogen broken down …

Answer 2

2% of skeletal muscle is glycogen;
10% of liver is glycogen;
Glycogen is made in the fed state;
Glycogen reserves last 24 hours of fasting, first energy reserve;
Glycogen is broken down (glycogenolysis) to form G6P;
Liver removes phosphate and resulting glucose released to circulation;
Skeletal muscle uses G6P (glycolysis) during exercise;

Question 3

Structure of glycogen

Answer 3

Linear chains formed from alpha 1, 4 glycosidic bonds between glucose units;
Branches formed by every 8-10 glucose units by alpha 1-6 glycosidic bonds;
Branched structure allows rapid breakdown;
Forms cytoplasmic granules containing enzymes of glycogen metabolism;

Question 4

Glycogen synthesis

Answer 4

Glucose 6 phosphate converted to glucose 1 phosphate;
Glucose transferred to UTP to form UDP-glucose;
Glycogen synthase creates alpha-1-4 glycosidic bonds to add glucose to a pre-existing glycogen fragment ‘seed’;
In the absense of seed, glucose transferred to glycogenin protein;

Question 5

Reducing and non reducing ends

Answer 5

Reducing end - anomeric carbon (C1) not linked to another glucose - free aldehyde group;
Non-reducing end - anomeric carbon (C1) in glycosidic bond, no free aldehyde group

Question 6

Glycogenolysis

Answer 6

In liver;
Glycogen converted to G6P;
Phosphate removed from G6P to form glucose which is then released into the blood;

Phosphorolysis of alpha 1,4 glycosidic blonds by glycogen phosphorylase using Pi to form G1P;
Stops 4 glycosyl units from branch point - results in limit dextrin;
Debrancing enzyme - moves all but one glucose molecule at branch to end of another chain - cleaves alpha- 1,6 glycosidic bond to yield a glucose;

Question 7

2 products of glucogenolysis and what they are converted to

Answer 7

Glucose 1 phosphate and glucose;
G1P converted to G6P;
Glucose phosphorylated to G6P;
G6P utilised in muscle;
Liver can remove phosphate from G6P (glucose 6 phosphatase) and release glucose to circulation;

Question 8

Regulation of glycogen metabolism

Answer 8

Glycogen is synthesized during the fed state in liver and while resting in muscle;
Allosteric and hormonal regulation of key enzymes;
Avoids futile cycle f synthesis and degradation;
Key regulatory enzymes are glycogen phosphorylase and glycogen synthase;

Question 9

Allosteric regulation of glycogen metabolism

Answer 9

High energy state (Liver):
Glucose high, G6P high, ATP high;
Glycogen phosphorylase inhibited by G6P, ATP, glucose;
Glycogen synthase activated by G6P;
Glycogen synthesis predominates;

Low energy state (Muscle):
Glucose Low, ATP Low, G6P low, muscle AMP high;
Muscle glycogen phosphorylase activated by AMP;
Glycogenolysis predominates;

Question 10

Glycogenolysis and Ca

Answer 10

Glycogenolysis in muscle activated by Ca;
Muscle contraction from increased cytosolic Ca;
Calcium binds to and activates phosphorylase kinase;
Phosphorylase kinase phosphorylated and activates glycogen phosphorylase;

Question 11

Hormonal regulation of glycogen metabolism

Answer 11

Key hormones: insulin, glucagon, adrenaline;
Hormones act through changes to phosphorylation state of enzymes;
Binding of hormones to cell surface receptor triggers intracellular events;
Adrenaline and glucagon act though second messenger - cyclic AMP (cAMP);

Question 12

G-protein coupled receptors

Answer 12

Glucagon and adrenaline bind to G protein coupled receptors (GPCRs);
These are proteins that span the cell membrane;
Binding of hormone trigger conformational change in receptor, transmitted to intracellular domain which allows binding of a G-protein;