Carbohydrate Metabolism

Question 1

What is Metabolic homeostasis?

Answer 1

The process of maintaining optimal metabolite concentrations and managing chemical energy reserves in tissues

Question 2

What is Catabolism ?

Answer 2

The degradative phase of metabolism; releases energy

Question 3

What is Anabolism (biosynthesis) ?

Answer 3

The building phase of metabolism: requires energy

Question 4

What is the Blood glucose ideally kept at ?

Answer 4

~4.5mM (70−100 mg/100mL), with some fluctuation occurring after a meal

Question 5

What is the brain most vulnerable ?

Answer 5

Hypoglycaemia as cerebral cells derive their energy predominantly from aerobic metabolism of glucose

Question 6

When the brain is vulnerable to hypoglycaemia, it cannot ?

Answer 6

• store glucose in significant amounts or synthesise glucose
• metabolise substrates other than glucose or ketone bodies
• extract sufficient glucose for their needs from the extracellular fluids at low concentrations because glucose entry into the
  brain is not facilitated by hormones

Question 7

Blood glucose varies relatively little over 24hr despite changes in food intake. Controlled by ?

Answer 7

Changes in circulating levels of insulin and glucagon

Question 8

Alterations in the ratio of

insulin:glucagon within the blood are essential for ?

Answer 8

The maintenance of blood glucose

Question 9

When is Glucose absorbed from the intestine ?

Answer 9

2-3 hours following a meal

Question 10

When is Glycogen degraded?

Answer 10

Between meals and and lasts for 12-24 hours

Question 11

During sleep/extended food deprivation there is a gradual dependence on ?

Answer 11

De novo glucose

synthesis by gluconeogenesis as glycogen stores are depleted

Question 12

Blood glucose is under strict homeostatic control, by two main hormones ?

Answer 12

Insulin and Glucagon

Question 13

Insulin stimulates ?

Answer 13

Glucose uptake and storage when levels are high

Question 14

Glucagon stimulates ?

Answer 14

Breakdown of stores/synthesis when levels are low

Question 15

How does glucose enter the cells ?

Answer 15

by facilitated diffusion i.e. it is a carrier-mediated process with glucose entering the cells down its concentration gradient

Question 16

How is the entry of glucose mediated ?

Answer 16

Entry mediated by a family of glucose transporter proteins (Gluts) which are structurally related but encoded by different genes that are expressed in tissue specific manner

Question 17

Explain GLUT 1 in detail and where it is found ?

Answer 17

• Found everywhere - all mammalian tissues
• Constitutive glucose transporter: basal glucose uptake
• High affinity (1mM), low capacity: glucose continually taken up at steady rate irrespective of the blood glucose concentration

Question 18

Explain GLUT 2 in detail and where it is found ?

Answer 18

• Found in the liver and pancreatic beta cells
• Low affinity (15-20mM), high capacity: rate of glucose entry is proportional to the glucose concentration
• High plasma glucose leads to accelerated glucose entry.
• Low affinity prevents glucose entering the liver when blood glucose is low, allowing glucose to preferentially enter brain and red blood cells

Question 19

Explain GLUT 3 in detail and where it is found ?

Answer 19

• Found mostly in the brain

- Supplements GLUT 1 in tissues with high energy demands

Question 20

Explain GLUT 4 in detail and where it is found ?

Answer 20

• Found in the skeletal muscle and adipose tissue
• Affinity ~5mM, therefore controlled by the blood glucose concentration.
• Insulin-dependent: increases the number of transporters on the plasma membrane (so high
  uptake when high blood glucose)

Question 21

Explain GLUT 5 in detail and where it is found ?

Answer 21

• Found in the small intestine

- This is a fructose transporter by facilitating fructose absorption by moving the sugar down a chemical gradient

Question 22

What is Glycogen ?

Answer 22

Polysaccharide storage form of glucose; mainly in liver and muscle

Question 23

What is difference between the way Liver glycogen and Muscle glycogen are used ?

Answer 23

Liver glycogen is used to maintain plasma glucose levels between meals, whereas muscle glycogen is used for contraction

Question 24

How is glycogen synthesised and degraded ?

Answer 24

• Glycogen is synthesised via glycogenesis

- Degraded via glycogenolysis, producing glucose-1-phosphate (G1P)

Question 25

In the liver, what can G1P be converted to ?

Answer 25

Free glucose via G6P and exported into the bloodstream to maintain plasma glucose levels

Question 26

Where is the G6P isolated ?

Answer 26

In the ER lumen, which allows use of concentration gradients for glucose and G6P to control flux out of the liver

Question 27

Which has a greater tissue content, the liver or muscle ?

Answer 27

The tissue content of glycogen is higher in liver than muscle

Question 28

Which has a greater muscle storage capacity, the liver or muscle ?

Answer 28

Muscle because of greater muscle mass

Question 29

Why does the liver contain less glycogen than is required?

Answer 29

To sustain glucose metabolism for 24 hours therefore require de novo synthesis by gluconeogenesis (We require 200g glucose/day)

Question 30

When can glycogen stores rise ?

Answer 30

After meal

Question 31

When do the glycogen stores fall ?

Answer 31

Between meals as glucose is released from glycogen to help maintain blood glucose levels

Question 32

After a meal, what is there an increase in ?

Answer 32

After a meal there is an increase in blood glucose; between meals it stabilises

Question 33

What happens overnight to the glycogen stores ?

Answer 33

Overnight glycogen

stores are mobilised to help maintain blood glucose levels, with increasing glucose coming from gluconeogenesis

Question 34

Explain the metabolism in the fed state (Liver) ?

Answer 34

• High concentrations of nutrients leads to an increase in the I:G ratio
• High blood glucose enters the liver and is converted to glycogen and triacylglycerols which are secreted as VLDL. Some enters TCA cycle
• Lactate returning from red blood cells and muscle, and glycerol from peripheral tissues, are also
  converted to triacylglycerols
• Excess amino acids entering from the gut are converted to pyruvate and metabolised via the TCA for energy or converted to triacylglycerols

Question 35

Explain the metabolism in the fed state (Muscle) ?

Answer 35

• Glucose enters the muscle via insulin-stimulated Glut 4 and is converted to glycogen or metabolised to produce acetyl CoA and energy
• Fatty acids entering muscle via chylomicrons and VLDL are oxidised by beta-oxidation to acetyl CoA to produce energy to support contraction
• Amino acids are incorporated into proteins

Question 36

Explain the metabolism in the fed state (Adipose tissue and Brain) ?

Answer 36

• Glucose enters adipose tissue by insulin-dependent Glut 4 and is converted via glycolysis and PDH into acetyl CoA and then to fatty acids and triacylglycerol
• Fatty acids enter from VLDL and chylomicrons and are converted to triacylglycerol
• Glycerol released from TAGs is returned to liver for re-use
• Brain takes up glucose via Glut 1 & 3 transporters and metabolises it oxidatively by
  glycolysis and the TCA cycle to produce energy