The Liver and gluconeogenesis

Question 1

Phsiological circulating glucose concentration

Average fasting glucose concentration

Answer 1

3. 9-6.2 mM

4. 4-5.0 mM

Question 2

Roles of Glucose

Answer 2

Source of Energy

Source of carbon for other sugars and glycoconjugates-
mannose, galactose, glucuronic acid

Source of pentose sugar for synthetic reactions (DNA)

Source of NADP- needed for synthetic reactions and drug mechanisms

Question 3

Advantages of having glucose-

Answer 3

Water soluble so no carrier required

Can cross the blood-brain barrier

Can be oxidised anaerobically

Question 4

Disadvantages of having glucose

Answer 4

Relatively low yield of ATP per mole compared to fatty acids

Osmotically active

in high concentration can directly damage cells/ lead to accumulation of toxic-by products

Question 5

Pathways involving glucose in skeletal muscles

Answer 5

Glycolysis—> Anaeorobic muscle contraction

Glycolysis/TCA —-> energy

glycogenesis—-> Energy store for muscle contraction

Question 6

Pathways involving glucose in Heart/Brain

Answer 6

glycolysis/TCA —> energy

Question 7

Pathways involving glucose in adipose tissue

Answer 7

Glycolysis —> production of glycerol phosphate for TAGs

FED STATE

Question 8

Pathways involving glucose in erthrocyte

Answer 8

Glycolysis—> energy

Pentose Phosphate—> NADPH

Question 9

Pathways involving glucose in liver

Answer 9

glycolysis/TCA cycle —> Production of acetyl CoA

Pentose phosphate—-> NADPH, pentose

Glycogen Synthesis/glycogenolysis—> Glucose storage for other tissues

Gluconeogenesis—> Glucose for other tissues

Question 10

Sources of Blood glucose

Answer 10

Diet
Liver glycogen
Liver gluconeogenesis

Question 11

Gluconeogenesis

Answer 11

When carbohydrate concentration low in the blood plasma

Glucose is synethesised from non carbohydrate sources

• other monosaccharides
• lactate
• Glycerol
• Glucogenic amino acids

Question 12

Gluconeogenesis is not simply the reverse of Glycolysis

Answer 12

Hexokinase
phosphofructokinase
Pyruvate kinase

Instead…

Glucose- 6-phosphate
fructose-1,6-phosphate
Pyruvate kinase, PEP carboxykinase

Question 13

How is gluconeogenesis regulated

Answer 13

Mobilisation of substrate- glycerol from fat breakdown
and amino acid from protein breakdown

Activation of enzymes-

G6 pase, fructose-1,6-phosphate, Pyruvate kinase, PEP carboxykinase

Acetyl CoA activates pyruvate carboxylase

Question 14

Which hormones maintain blood glucose

Answer 14

Insulin, glucagon, adrenaline, glucose ALL signal and coordinate liver, adipose, muscle tissue

Question 15

Insulin

Answer 15

anabolic hormone- synthesis and storage

Question 16

Glucagon

Answer 16

catabolic hormone- degradation of stored fuel

Question 17

Metabolic effects of insulin- liver

Answer 17

Inhibits gluconeogenesis

Activation of glycogen synthesis- glycogen synthase activated

Increase in FA and lipid assembly

Increase in aa uptake and protein synthesis

Question 18

Liver Fed state

Answer 18

glucose—> glc-6-P—>glc-1-P—> glycogen

glucose—> glc-6-P—>pyruvate—> acetyl CoA—> FA—> fatty acid

Question 19

Metabolic effects of Insulin- Muscle

Answer 19

increase in glucose uptake by GLUT 4

increase in aa uptake - protein synthesis

activation of glycogen synthesis- glycogen synthase activates

Question 20

Muscle- Aerobic

Answer 20

glucose–> glc-6-P

glycogen—> glc-1-P—> glc-6-P

glc-6-P—> pyruvate—> acetyl CoA—TCA, Ox Phos—> ATP

Question 21

Metabolic effects of glucagon

Answer 21

Increase in blood glucose—> increase in glycogenolysis and increase in gluconeogenesis

Increase in circulating fatty acid and ketone bodies–> increase in adipose tissue lysis, increase in fatty acid oxidation in the liver and ketone body formation

Increase in plasma amino acids—> increase in uptake for gluconeogenesis

Question 22

Liver- fasting state

Answer 22

Glycogen—> glc-1-P—> glc-6-P—> glucose
Fat—> FA—> acetyl CoA—> pyruvate—> glc-6-P—> glucose

Lactate—> pyruvate —> glc-6-P—> glucose

Question 23

Brain: fasting and fed state

Answer 23

glucose—> glc-6-P—>pyruvate—> acetyl CoA—>TCA, OX PHOS—> ATP

Question 24

Erythrocyte: FED FASTING

Answer 24

glucose—> glc-6-P—>pyruvate—>Lactate