The Liver and Glucose Homeostasis Flashcards
what are the functions of the liver
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
what is the fuel for metabolism
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
how is the fuel for metabolism used
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)
Roles of liver and adipose tissues in handling of dietary fuels
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
what are the main energy stores
proteins for amino acids
glycogen for glucose
triacylglycerols for fatty acids
how is glucose the energy major substrate
Constantly replenished in blood to prevent hypoglycaemia via liver (glycogen breakdown and gluconeogenesis) and diet
how is glucose needed for brain
Most vulnerable to hypoglycaemia as cerebral cells derive energy predominantly from aerobic metabolism of glucose
why is glucose needed for the brain
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
Mechanisms controlling blood glucose (increase)
gluconeogenesis (synthesis from non-carbs)
glycogenolysis (mobilise liver stores)
inc by glucagon, catecholamines, cortisol and growth hormones
Mechanisms controlling blood glucose (decrease)
glycolysis (oxidise glucose by peripheral tissues)
glycogen and fat synthesis (convert glucose to glycogen and fat)
dec by insulin
sources of blood glucose
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
Hormonal control of blood glucose
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
Blood glucose in homeostasis
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
Entry of glucose into cells from blood
Glucose entry into cells is major and important metabolic effect of insulin
Polar – needs to cross lipid membrane, active or passive
Glucose transport into tissues
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
Glut 1
Glut 1 found in many tissues eg erythrocytes, muscle, brain, kidney, colon, placenta, foetal tissue
Glut 2
Glut 2 found in liver and pancreatic b cells
Glut 3
Glut 3 found in brain
Glut 4
Glut 4 found in skeletal muscle, adipose tissue (insulin-sensitive)
Glut 5
Glut 5 found in SI, fructose transporter
Glucose transport by tissue type
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)
Insulin regulation of glucose entry into tissues
Glut 4 in cytoplasm of cells (respond to insulin), all others in membrane to control entry
Immediate cellular effects of insulin
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
long-lasting cellular effects of insulin
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
Pentose phosphate pathway – another important use of glucose
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
how does the pentose phosphate pathway vary between cells
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
Tissue specific glucose metabolism
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
