biochem - feast/starve cycle Flashcards
brain derives energy from…
glucose and ketone bodies only
cannot use FA
glucose levels for
- normal
- renal threshold
- diabetic coma
- overnight fast
- hypoglycemia
-normal 8 mM
-renal threshold at 10mM –> glucosuria, excess urination
-diabetic coma 60 mM
-overnight = 5 mM
-
after a meal glucose from where 0-4 hrs up to 24 hrs starting at 8 hrs
gut
liver glycogen
gluconeogenesis - dominant process at 16 hrs
insulin
polypeptide secreted by beta cells in pancreas in response to elevated blood glucose
SIGNALS well fed state and promotes increased transport of glucose into adipose and muscle, glycogen synthesis, de novo TG synthesis, deposition of fat, and protein synthesis
-inhibits breakdown of fat, protein, and glycogen
glucagon
made from alpha cells in pancreas in response to low blood glucose, low insulin
signals fasting state and promotes glycogenolysis, lipolysis, and gluconeogenesis
where is there no glucagon receptor (so no effect on)?
muscle
in pancreas glucose binds and causes
glucagon to go down, and insulin to go up
liver fat production
in liver glucose can be converted to triacylglycerols and packged into VLDLs and released into blood –> FAs of VLDLs are stored in adipose tissue
intestinal triacylglycerol absorption
packaged into chylomicrons and secreted into lymph into blood
insulin activates which transporter?
GLUT4 on muscle and fat tissue
RBCs require
glucose
oxidize it to pyruvate and lactate
no mitochondria
what vessel transports aa and glucose to liver
hepatic portal vein
in liver, what activates... 1- glucose transport 2-glycogen storage 3-glycogen breakdown 4-FA synthesis 5- FA oxidation 6-glycolysis 7 - gluconeogenesis
1 - insulin and glucagon both have no effect on transport
2 - insulin activates glycogen storage
3 - glucagon activates glycogen breakdown
4 - insulin activates FA synthesis
5 - glucagon activates FA oxidation
6 - insulin activates glycolysis
7 - glucagon acivates gluconeogenesis
in adipose, what inhibits
1- glucose transport
2 - TG deposition
3- TG mobilization
1 - glucagon inhibits glucose transport in fat
2 - glucagon inhibits TG deposition in fat
3 - insulin inhibits TG mobilization; glucagon ACTIVATES TG mobilization
in muscle, what enzyme works? what is its effect on... glucose transport glycogen synthesis glycogen breakdown protein synthesis protein breakdown
insulin only
activates - glucose transport, glycogen synthesis, protein synthesis
inhibits - glycogen breakdown and protein breakdown
TGs of chylomicrons and VLDL
where are each produced? and where are they digested/by what?
chylomicrons are made from dietary fat and VLDL is made from glucose in liver
digested in capillaries by lipoprotein lipase to form FAs and glycerol –> stored by adipose as TGs
as blood glucose decreases…insulin? and glucagon?
insulin decreases and glucagon increases –> stimulating release of stored fuels into blood
when in fasting state, the liver…
supplies glucose and KB to the blood
it maintains blood glucose via glycogenolysis and gluconeogenesis and makes ketone bodies from FAs of adipose
2 ketone bodies?
B-hydroxybutyrate
acetoacetate
ketone bodies have a _____ ______ effect
protein sparing
what happens 2-3 hrs after a meal to release glucose into blood
glycogenolysis - glycogen is broken down;
glycogen stores deplete within 30 hrs
what happens 4-6 hrs after a meal?
gluconeogenesis
gluconeogenesis carbon sources
lactate from RBCs or exercising muscle
glycerol from TGs of adipose breakdown
AAs (alanine) from muscle protein
propionate from oxidation of odd chain FAs
ketone body formation
adipose tissue breaks down TGs in response to rising glucagon
FAs and glycerol are released
B oxidation converts the FAs to acetyl coA which is used in liver to make KBs
muscle release ____ in fasting state
aa
the carbons are used for gluconeogenesis and the nitrogen is converted to urea
in starvation…
muscles decrease use of KBs so KB [ ] in blood goes up and brain can use them for energy so that it requires less glucose
gluconeogenesis slows down which spares muscle protein and produces less urea than an overnight fast!
body uses mostly fat when in starvation
two places where gluconeogenesis occur?
liver and kidney cortex
cori cycle
cycling of Lactate produced by red blood cells during anaerobic respiration in the muscles back into glucose.
The lactate produced by the muscle anaroebic glycolysis (glucose to lactate to produce atp) is cycled into the liver through the blood. In the liver it is converted to pyruvate by lactate dehydrogenase. The pyruvate is then cycled back into glucose by gluconeogenesis (using atp) and recycled back into the blood for use by red blood cells and muscles.
The Cori Cycle is significant two fold; it is neccesary to prevent lactic acidosis and in the conservation of oxygens being carried by erythrocytes(red blood cells). Because erythrocytes do not contain mitochondria, any aerobic respiration they would undertake would require the use of the oxygen they are transporting, which would negate the transport.
major gluconeogenesis precursors?
aa
lactate
glycerol
things that cant be converted to glucose
acetyl coA
even chain FAs
KBs
ethanol
how is gluconeogenesis different from glycolysis
not just a simple reversal
3 irreversible steps are bypassed (all are kinases)
the three irreversible steps of glycolysis
glucokinase (glucose + atp –> G6p + adp)
pfk-1 (f1p + atp –> F16BP + adp)
pyruvate kinase (PEP + adp –> pyr + atp)
where is alanine converted to pyruvate?
mito matrix
In gluconeogenesis, pyruvate carboxylase converts….what to what and where?
pyruvate –> oxaloacetate in the mitochondrion
in gluconeogenesis, oxaloacetate is converted to either ____ or _____ by what?
malate by malate dehydrogenase
aspartate by transaminase
in gluconeogenesis, malate/aspartate travel _____ where they_____
to cytosol
reconverted to oxaloacetate
there is no transporter for ____ so ___ is used
oxaloacetate
malate-aspartate shuttle
biotin
cofactor that carries activated CO2 during two step reaction of pyruvate carboxylase
two step reaction of pyruvate carboxylase
and net
E-biotin + ATP + CO2 + H2O –> E-carboxybiotin + ADP + Pi
E-carboxybiotin + pyruvate –> oxaloacetate + E biotin
Net = ATP + pyruvate + CO2 + H20 –> oxaloacetate + ADP + Pi
ATP is driving force
key regulatory enzyme of gluconeogenesis
what does it reqiure?
pyruvate carboxylase
-requires acetyl coA as a positive allosteric activator
what is the positive allosteric activator of pyruvate carboxylase?
acetyl CoA
in live: fasting –> elevated acetyl coa –> gluconeogenesis is activated
PEPCK
phosphoenolpyruvate carboxykinase
converts oxaloacetate to phosphoenol pyruvate (PEP)
first bypass reaction pyruvate to PEP
PEP forms…
is made by
F 1,6 BP by reversal of glycolysis
PEPCK from oxaloacetate
second bypass reaction
F16BP –> fructose 6 phosphate
by fructose 16bisphosphatase
F6p can then become g6p
third bypass reaction
glucose 6 phosphate –> glucose
by glucose 6 phosphatase
importance of glucose 6 phosphatase
allows liver to export glucose
g6p cannot leave cell since it isnt recognized by GLUT transporter
what enzymes are inactive during gluconeogenesis
pyruvvate dehydrogenase
pyruvate kinase
PFK1
glucokinase
–these are the 4 used in glycolysis that are bypassed
—ensures that pyruvate becomes glucose and avoids futile cycle
only sounds of energy during gluconeogenesis to liver?
oxidation of FA
glycolysis is inactive to avoid futile cycle
synthesis of 1 mol glucose requires ____ mol lactate? and ____ mol ATP?
2 mol lactate
6 mol atp
gluconeogenesis starting with aa
aa –> pyruvate —(pyruvate carboxylase)-> OAA
OAA —-(PAP carboxykinase) —->PEP
PEP ——> G3P (glyceraldehyde 3 phosphate)
glycerol –> G3P –> DHAP
DHAP /G3P ——> Fructose 1,6 Phosphate
F16P —(fructose 1,6 bisphosphotase) —-> F6P
F6P —->G6P
G6P —(glucose 6 phosphotase) —-> glucose
