Liver & Glucose Homeostasis Flashcards
Biomolecules as energy stores
Fuel Metabolism: Energy for ATP synthesis derived from the oxidation of 3 main body fuels:
- glucose stored as glycogen
- long chain fatty acids stored as
triacylglycerol - amino acids
- obtained intermittently from meals yet
required continuously
What kind of proteins can enter the citric acid cycle?
Deaminated (remove nitrogen)
2 requirements of fuel metabolism:
1) store fuels when abundant
2) release fuels in a controlled way during
the post-absorptive period, during
exercise or starvation
Phases of assimilation:
1) immediate absorptive events
2) post-absorptive events
Phases of assimilation: Immediate absorptive state:
- liver and adipose tissue mainly take up
materials - glycogen
Phases of assimilation: Post-absorptive state:
- mobilisation of reserves of glycogen built up during feeding
Functions of the liver (9):
- store glycogen
- break down glycogen
- deaminates surplus amino acids and
converts amino groups into ammonia and
then urea - synthesise glucose from non-carb
precursors - synthesise ketone bodies and secrete for
fuel for other tissues - aid elimination of cholesterol from the
body and synthesises bile salts from
cholesterol - stores fat soluble vitamins ADEK
- metabolism and elimination of drugs
Ketone bodies:
- produced from fatty acid breakdown
- acetoacetate
- beta-hydroxybutyrate
- acetone
Liver and Ketone Bodies:
- selfless
- synthesise ketone bodies but can not
utilise them as an energy source
hypoglycaemia
low plasma glucose concentration
Glucose metabolism
Glucose metabolism and the Brain:
- the brain is most vulnerable to
hypoglycaemia as cerebral cells derive their
energy predominantly from aerobic
metabolism - Brain can not (3):
- store glucose in significant amounts or
synthesise glucose - metabolise substrates other than glucose
or ketone bodies - extract sufficient glucose for their needs
from extracellular fluids at low concs
because glucose entry into the brain is
not facilitated by hormones
- store glucose in significant amounts or
Why does RBCs need so much glucose?
- no mitochondria present
- can only use glycolysis no oxidative
phosphorylation
Glycogenolysis
mobilisation of liver glycogen stores
Gluconeogensis
glucose syntehsis in liver and kidneys from non-carb precursors eg amino acids, glycerol, lactate
Glycolysis
Oxidation of glucose by peripheral tissues
Mechanisms controlling blood glucose:
Insulin primary mechanism
increase absorption of cells to glucose
Pancreas and Insulin Secretion:
- blood glucose high -> high ATP in beta cells
in the Islets of Langerhans - Closes K+ channels and depolarises
membranes - Voltage gated Ca2+ channels open in
response allowing Ca2+ to flow into the cell
Alpha cells in the Islets of Langerhans (pancreas) secrete
glucagon (alphabetical both first)
Beta cells in the Islets of Langerhans (pancreas) secrete
insulin (alphabetical both second)
Blood glucose varies a lot throught the day and night due to changes in food intake.
True or False?
False
varies relatively little
controlled by fluctuations in circulating levels of insulin or glucose
When dietary glucose intake is low,
glycogenolysis is high
gluconeogenesis is high before eating (mainly night)
Glucose is absorbed from the intestine for how many hours following a meal?
2-3 hours
Glycogen is degraded between meals and lasts for
12-24 hours
Glucose homeostasis
insulin stimulates
the entry of glucose into cells is the major and most important metabolic effect of insulin
How do polar molecules such as glucose enter cells, across a lipid membrane?
Antelded
Glucose enters cells by:
- passive diffusion
- facilitated diffusion
- active transport
facilitated diffusion (down conc grad)
Family of glucose transporter proteins are structurally related but
encoded by different genes that are expressed in a tissue specific manner
Glucose transport into tissues: Glut 1:
- many tissues
- erythorocytes
- muscle
- brain
- kidney
- placenta etc
Glucose transport into tissues: Glut 2:
- liver
- pancreatic beta cells
Glucose transport into tissues:: Glut 3:
- brain
Glucose transport into tissues: Glut 4:
- skeletal muscle
- adipose tissue
**insulin sensitive
Glucose transport into tissues: Glut 5:
- small intestine
- (fructose not glucose transporter)
All cells express at least on isoform of glucose transporter proteins (Gluts).
True or False?
True
a certain level of glucose uptake is an absolute necessity
Glucose transporters
Insulin Regulation of Glucose Entry into Tissues:
- insulin binds to insulin receptor
- causing auto-phosphorylation
- changing conformation of insulin receptor
on the inside of the cell - through cascade reactions results in the
inhibition of lipolysis
Cellular effects of insulin:
Immediate effects:
- increase in the rate of glucose uptake in
muscle and adipocytes
- modulation of activity of enzymes involved
in glucose metabolism
(occur in minutes, does not require protein synthesis, occurs at insulin 10-9 or -10 mols/L)
Long lasting effects:
- increased expression of liver enzymes that
synthesize glycogen
- increased expression of adipocyte
enzymes that synthesize triacylglycerols
- inhibits lipolysis in adipose tissues by
inactivating hormon-sensitive lipase which
mobilises fatty acids from TG stores
- functions as a growth factor for some cells
eg fibroblasts
(occur over several hours, require continous exposure to insulin at 10-8 mol/L)
Pentose Phosphate Pathway
- cytosolic pathway in all cells
- branches from glycolysis at G6P
- Products:
- ribose phosphate: synthesizes RNA/DNA
- NADPH: biosynthesis, maintain redox
balance of cell
Tissues involved in biosynthesis (liver, adipose) are rich in
PPP enzymes (pentose phosphate pathway)
in cells where biosynthetic processes are less active, PPP intermediates are
recycled back into glycolysis
Fate of glucose in muscle and heart
Fate of glucose in Liver
- Glut2
- stored as glycogen, glycolysis to form
pyruvate and then acetyl CoA - some to produce ATP, excess acetyl CoA
used for fat synthesis - some goes through PPP pentose
phosphate pathway to form NADPH to
support fat biosynthesis
Fate of Glucose in the Liver
Fate of glucose in the brain:
- Glut1 & Glut3
- aerobic metabolism to produce energy
- some used in pentose phosphate pathway
to provide NADPH for lipid synthesis
Fate of Glucose in Brain
Fate of Glucose in Adipose Tissue:
- Glut 4
- glycolysis to produce acetyl CoA to produce
ATP or synthesise fats - some used for pentose phsophate
pathway to produce NADPH also required
for fatty acid synthesis
Fate of Glucose in Adipose tissue
Fate of Glucose in Main Body Tissues:
RBCs: Glut 1: glycolysis to lactate to produce energy
- some used in pentose phosphate pathway
to produce NADPH for the maintenance of
reduce glutathione - RBCs do not have mitochondria and
therefore can not oxidise glucose fully via
the TCA cycle and the ETC - must rely on glycolysis of glucose alone for
energy requirements
Fate of Glucose in Main Body Tissues
