The Liver and Glucose Homeostasis

Question 1

what are the functions of the liver

Answer 1

stores glycogen and breaks it down to release glucose
synthesise glucose from non-carbs
dominates surplus amino acids
synthesise fatty acids
synthesise ketone bodies
aids in cholesterol elimination
stores fat soluble vitamins
major site for metabolism/elimination of drugs/toxins

Question 2

what is the fuel for metabolism

Answer 2

All processes that keep the body functioning require energy (ATP)
Derived from oxidation of 3 main body fuels
Glucose (stored as glycogen)
Long chain fatty acids (stored as triacylglycerol)
Amino acids (mainly in proteins)
Obtained intermittently from meals, energy for body processes required continuously

Question 3

how is the fuel for metabolism used

Answer 3

First requirement is store fuels when abundant
Second is to release in a controlled way during postabsorptive period, during exercise or increased demand (eg illness or starvation)

Question 4

Roles of liver and adipose tissues in handling of dietary fuels

Answer 4

After a meal
Immediate absorptive events eg immediate fate of dietary compounds, liver and adipose tissues mainly take up materials (import)
Post-absorptive events eg between meals, cells of liver and adipose tissue export

Question 5

what are the main energy stores

Answer 5

proteins for amino acids
glycogen for glucose
triacylglycerols for fatty acids

Question 6

how is glucose the energy major substrate

Answer 6

Constantly replenished in blood to prevent hypoglycaemia via liver (glycogen breakdown and gluconeogenesis) and diet

Question 7

how is glucose needed for brain

Answer 7

Most vulnerable to hypoglycaemia as cerebral cells derive energy predominantly from aerobic metabolism of glucose

Question 8

why is glucose needed for the brain

Answer 8

Store glucose in sig amounts or synthesise it
Metabolise substrates other than glucose or ketone bodies
Extract sufficient glucose for needs from extracellular fluids at low conc because glucose entry to brain is not facilitated by hormones

Question 9

Mechanisms controlling blood glucose (increase)

Answer 9

gluconeogenesis (synthesis from non-carbs)
glycogenolysis (mobilise liver stores)
inc by glucagon, catecholamines, cortisol and growth hormones

Question 10

Mechanisms controlling blood glucose (decrease)

Answer 10

glycolysis (oxidise glucose by peripheral tissues)
glycogen and fat synthesis (convert glucose to glycogen and fat)
dec by insulin

Question 11

sources of blood glucose

Answer 11

glucose absorbed from intestine for 2-3 hours after meal
glycogen degraded between meals, lasts for 12-24 hours
during sleep or food deprivation there is inc reliance on gluconeogenesis

Question 12

Hormonal control of blood glucose

Answer 12

Blood glucose varies relatively little throughout day and night despite changes in food intake, mainly controlled by fluctuations in circulating levels of insulin and glucagon
Alterations in the ratio in blood essential to maintain blood glucose

Question 13

Blood glucose in homeostasis

Answer 13

inc - insulin released from B cells in pancreas so its turned to glycogen, fat or energy
dec - glucagon from a cells in pancreas so glycogen converted to glucose by gluconeogenesis

Question 14

Entry of glucose into cells from blood

Answer 14

Glucose entry into cells is major and important metabolic effect of insulin
Polar – needs to cross lipid membrane, active or passive

Question 15

Glucose transport into tissues

Answer 15

Glucose enters cells by facilitated diffusion eg carrier-mediated process with glucose entering cells down conc gradient
Entry involves a family of glucose transporter proteins with are structurally related but encoded by different genes that are expressed in tissue specific manner
All cells express at least 1 Glut as certain level of glucose uptake required

Question 16

Glut 1

Answer 16

Glut 1 found in many tissues eg erythrocytes, muscle, brain, kidney, colon, placenta, foetal tissue

Question 17

Glut 2

Answer 17

Glut 2 found in liver and pancreatic b cells

Question 18

Glut 3

Answer 18

Glut 3 found in brain

Question 19

Glut 4

Answer 19

Glut 4 found in skeletal muscle, adipose tissue (insulin-sensitive)

Question 20

Glut 5

Answer 20

Glut 5 found in SI, fructose transporter

Question 21

Glucose transport by tissue type

Answer 21

Different affinity for glucose, uptake determined by concentration of glucose in blood
High affinity (Glut 1 and 3) take up irrespective of conc in blood, low affinity (Glut 2 and 4) more affected (only take up when high to conserve for other tissues)

Question 22

Insulin regulation of glucose entry into tissues

Answer 22

Glut 4 in cytoplasm of cells (respond to insulin), all others in membrane to control entry

Question 23

Immediate cellular effects of insulin

Answer 23

Immediate effects – inc rate of glucose uptake in muscle and adipocytes
Modulate activity of enzymes involved in glucose metabolism
These effects occur in mins, do not require protein synthesis, occur at insulin conc of 10 -9/10

Question 24

long-lasting cellular effects of insulin

Answer 24

Inc expression of liver enzymes that synthesis glycogen
Inc expression of adipocyte enzymes that synthesise triacylglycerols
Inhibit lipolysis in adipose tissue
Function as growth factor for some cells eg fibroblasts
These effects
Occur in several hours, cont exposure to insulin, 10-8M

Question 25

Pentose phosphate pathway – another important use of glucose

Answer 25

Cytosolic pathway present in all cells
Branches from glycolysis at G6P
Two products
Ribose phosphate – used to synthesise RNA and DNA
NADPH – used for reductive biosynthesis and maintain redox balance of cell

Question 26

how does the pentose phosphate pathway vary between cells

Answer 26

Tissues involve biosynthesis (eg liver, adipose tissues) are rich in PP enzymes
Less active, PP intermediates (glyceraldehyde-3-phosphate and fructose-6-phosphate) are recycled back into glycolysis

Question 27

Tissue specific glucose metabolism

Answer 27

Muscle and heart – glycolysis, TCA, ETC
Excess glucose to glycogen
Some G6P for PP, pyruvate interchangeable with lactate
Liver – same as above but can used Acetyl CoA to make fat
Brain – all aerobic, no lactate
No glycogen as can’t store, some PP
RBCs – anaerobically = lactate, no mitochondria, some PP
Adipose tissue -
Glycolysis
Excess acetyl CoA to fat