Chapter 9- Carbohydrate Metabolism I Flashcards
what drives glucose entry into most cells
concentration (in peripheral blood its supposed to be 5.6mM– between 4 and 6mM)
glucose transporters
GLUT 1 GLUT 2**** GLUT 3 GLUT 4**** ****Most important b/c located in specific cells and are highly regulated
GLUT 2
low affinity transporter in hepatocyes (liver cells) and pancreatic cells.
in the hepatic portal vein (from spleen to liver) and captures excess glucose for storage, unless blood needs it… then it continues to the liver and goes into peripheral circulation.
GLUT 2 and glucokinase
serve as glucose sensor for insulin release
GLUT 4
in adipose tissue and muscle and responds to glucose concentration in peripheral blood. insulin stimulates movement of additional GLUT 4 transporters to the membrane by a mechanism involving exocytosis. these transporters will be saturated when blood glucose levels are a bit higher than normal.
type 1 and type 2 diabetes mellitus
1: insulin is absent and cannot stimulate the insulin receptor.
2: receport becomes insensitive to insulin and fails to bring GLUT 4 transporters to the cell surface
* glucose rises in both cases*
compare/contrast GLUT 2 and GLUT 4
GLUT 2 (liver/pancreas, Km = 15, not responsive to insulin but it acts as a glucose sensor to cause release of insulin in pancreatic B-cells) GLUT 4 (adipose/muscle, Km = 5, responsive to insulin)
how does insulin promote glucose entry into cells?
GLUT 4 is saturated when glucose levels are only slightly above 5mM, so glucose entry can only be increased by increasing the number of transporters. Insulin promotes the fusion of vesicles containing preformed GLUT 4 with the cell membrane.
which cells are capable of performing glycolysis?
every cell. even red blood cells because no mitochondria are required.
glycolysis
cytoplasmic pathway that converts glucose into 2 pyruvates. (releases a bit on energy through 1 phosphorylation and 1 redox reaction).
*in the liver glycolysis is part of the process by which excess glucose is converted to fatty acids for storage.
5 important enzymes in glycolysis
- hexokinase and glucokinase
- phosphofructokinases (PFK-1 and PFK-2)
- glyceraldehyde-3-phosphate dehydrogenase
- 3-phosphoglycerate kinase
- pyruvate kinase
rate-limiting enzyme for glycolysis
PFK-1
rate-limiting enzyme for fermentation
lactate dehydrogenase
rate-limiting enzyme for glycogenesis
glycogen synthase
rate-limiting enzyme for glycogenolysis
glycogen phosphorylase
rate-limiting enzyme for gluconeogenesis
fructose-1,6-bisphosphatase
rate-limiting enzyme for pentose phosphate pathway
glucose-6-phosphate dehydrogenase
first step in glucose metabolism for any cell
transport glucose across cell membrane and phosphorylate it by kinase enzymes to “trap” it in the cell
hexokinase
phosphorylates glucose to form glucose-6-phophate “trapping” it in the cell. low Km. inhibited by its own product. irreversible process.
glucokinase
phosphorylates and “traps” glucose in liver and pancreas cells, and works with GLUT 2 as part of the glucose sensor in B-islet cells. high Km. in liver cells its induced by insulin. irreversible process.
PFK-1
phosphorylates fructose 6-phosphate to fructose 1,6-bisphosphate using ATP. inhibited by ATP, citrate, and glucagon. activated by AMP, product, and insulin. irreversible process.
PFK-2
mainly in liver. activates PFK-1 and allows cells to override inhibition caused by ATP so glycolysis can continue even when cell is energetically satisfied.
glyceraldehyde-3-phosphate dehydrogenase
generates NADH while phosphorylating glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate. reversible process.
3-phosphoglycerate kinase
performs a substrate-level phosphorylation, transferring a phosphate from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate. reversible process.
pyruvate kinase
performs another substrate-level phosphorylation, transferring a phosphate from phosphoenolpyruvate (PEP) to ADP, forming ATP and pyruvate. activated by fructose 1,6-bisphosphate. irreversible process.
feed-forward activation
product of an earlier reaction of glycolysis stimulates a later reaction in glycolysis
Lactate dehydrogenase
Oxidizes NADH to NAD+, replenishing oxidized coenzymes for glyceraldehyde-3-phosphate dehydrogenase and reduces pyruvate to lactate
main result of fermentation
replenishing NAD+
3 intermediates of glycolysis used for other purposes
- dihydroxyacetone phosphate (DHAP) used in hepatic and adipose tissue for triacylglycerol synthesis.
2/3. 1,3-bisphosphoglycerate (1,3-BPG) and phosphoenolpyruvate (PEP) are high energy intermediates used to generate ATP by substrate level phosphorylation. only ATP gained in anaerobic respiration
3 irreversible processes of glycolysis
How Glycolysis Pushes Forward the Process: Kinases
Hexokinase, Glucokinase, PFK-1, Pyruvate Kinases
how many net ATP results from glycolysis
2
bisphosphoglycerate mutase
red blood cells have this. produces 2,3-BPG in glycolysis (which binds allosterically to B-chains of HbA and decreases its affinity to oxygen).
mutases
enzymes that move a functional group from one place in a molecule to another
what does exercise do to the pO2 curve?
RIGHT shit (exercise is the RIGHT thing to do)
what does 2,3-BPG do?
binds to hemoglobin and decreases its affinity for O2
how do monosaccharides reach the liver?
hepatic portal vein
3 important enzymes in galactose metabolism
- lactase: breaks up (hydrolyzes) lactose into glucose and galactose (first enzyme used in galactose metabolism)
- galactokinase: adds phosphate to galactose to trap it in the cell
- galactose-1-phosphate uridyltransferase: turns galactose 1-P into glucose 1-P
epimerases
enzymes that catalyze the conversion of one sugar epimer (diastereomers) to another
3 important enzymes in fructose metabolism
- sucrase: breaks up sucrose into glucose and fructose (fructose can also come straight from fruits and honey)
- fructokinase: phosphorylates fructose in the liver to trap it in the cell
- Aldolase B: cleaves fructose-1-P into DHAP and glyceraldehyde
what happens to pyruvate at the end of glycolysis
- conversion to acetyl-CoA by PDH for citric acid cycle (if ATP is needed) or fatty acid synthesis (if enough ATP)
- conversion to lactate by lactate dehydrogenase (anaerobic respiration)
- conversion to oxaloacetate by pyruvate carboxylase (to enter gluconeogenesis when there is a build up of acetyl-CoA)
pyruvate dehydrogenase
in liver. activated by insulin. turns pyruvate into acetyl-CoA using NAD+ and CoA. it also releases CO2 (actually a complex of enzymes carrying out multiple reactions in succession). inhibited by acetyl-CoA
importance of thiamine
pyruvate cannot be converted into acetyl-CoA without thiamine (vitamin B1)
where do glycogen synthesis and degradation occur?
mainly in liver (broken down to maintain constant level of glucose in blood) and skeletal muscle (broken down to provide glucose to muscle during vigorous exercise). glycogen is stored in cytoplasm as granules
steps in glycogenesis
synthesis of glycogen granules
- hexokinase phosphorylates glucose to glucose-6-phosphate
- phosphoglucomutase moves phosphate from 6 position to 1 position.
BRANCHING ENZYME - glucose 1-phosphate is converted to UDP-glucose (catalyzed by enzyme UDP glucose pyro phosphorylase… 2 phosphates are lost in process)
- UDP-glucose is converted to glycogen using enzyme GLYCOGEN SYNTHASE
glycogen synthase
rate-limiting enzyme of glycogen synthesis and forms a-1,4 glycosidic bond found in linear glucose chains of glycogen granules.
- stimulated by glucose 6-phosphate and insulin
- inhibited by epinephrine and glucagon
branching enzyme
responsible for introducing a-1,6-linked branches into glucose chain granules as it grows.
3 primary enzymes in glycogenolysis
- glycogen phosphorylase (breaks a-1,4 glycosidic linkage (CANT BREAK a1,6-bond, from nonreducing end)–activated by glucagon in liver. in skeletal muscle its activated by AMP and epinephrine. inhibited by ATP
- glycogen debranching enzyme (made up of 2 enzymes that break a 1,4 bond near the branch point and forms a new 1,4 bond, then hydrolyzes the a-1,6 bond leaving a free glucose residue)
- phosphoglucomutase (glucose-1-phosphate to glucose-6-phosphate
isoforms
slightly different versions of the same protein (ex: slightly different in the liver and muscle)
gluconeogenesis
(reversal of glycolysis) metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids (primarily performed by liver)
what promotes and inhibits gluconeogenesis
promoted by glucagon and epinephrine (to raise blood sugar levels)
inhibited by insulin (to lower blood sugar levels)
gluconeogenesis substrates
glycerol 3- phosphate (from stored fats, triglycerides in adipose tissue)
lactate (from anaerobic glycolysis)
glucogenic amino acids (from muscle proteins– all amino acids except for leucine and lysine)
fatty acids with an odd number of carbon atoms
these turn into glucose yet also yield a small amount of propionyl-CoA, which is glucogenic (can be converted to glucose)
pyruvate carboxylase
mitrochondrial enzyme activated by acetyl-CoA. converts pyruvate into oxaloacetate (OAA). when massive amounts of OAA are produced this will eventually lead to glucose production for the rest of the body.
phosphoenolpyruvate carboxykinase (PEPCK)
in cytoplasm is induced by glucagon and cortisol (acts to raise blood sugar levels). converts OAA to phosphoenolpyruvate. requires GTP.
fructose-1,6-bisphosphatase
in cytoplasm is a key control point of gluconeogenesis and is rate-limiting step. hydrolyzes phosphate from fructose 1,6-bisphosphate to produce fructose-6-phosphate.
activated by ATP
inhibited by AMP and fructose2,6-bisphosphate
phosphatases and kinases
they typically oppose each other
glucose-6-phosphatase
found only in lumen of the ER in liver cells. can be used for blood glucose. removes phosphate from glucose — converts glucose 6-phosphate into glucose (opposite of glucokinase and hexokinase)
amino acid glucogenics
converted into citric acid cycle intermediates, then to malate, following the same path from there to glucose
what is hepatic gluconeogenesis dependent on?
B-oxidation of fatty acids in the liver
why would the body need to carry out gluconeogenesis?
fasting for more than 12 hours
Pentose phosphate pathways (PPP)
aka: hexose monophosphate (HMP) shunt. occurs in cytoplasm of all cells.
two major functions: production of NADPH and serving as a source of ribose 5-phosphate for nucleotide synthesis (irreversible).
glucose-6-phosphate dehydrogenase (G6PD)
produces NADPH and is rate-limiting enzyme.
induced by insulin (b/c abundance of sugar entering cell under insulin stimulation will be shunted into glycolysis and aerobic respiration as well as storage (fatty acid synthesis, glycogenesis, PPP) …also activated by NADP+
inhibited by NADPH
hemolysis
rupture or destruction of red blood cells
radical formation and glutathione
H2O2 is a byproduct in aerobic metabolism and can break apart to form OH radicals (attack lipids, including phospholipid bilayer) and O2 radicals damage DNA (which can cause cancer)
Gutathione: reducing agent taht can help reverse radical formation before damage is done to the cell
3 primary functions of NADPH
- biosynthesis of fatty acids and cholesterol
- bleach production in white blood cells (bactericidal activity)
- maintenance of glutathione supply
