(L3) - Carbohydrate Metabolism Flashcards
What cell types exclusively use glucose as their fuel source?
L3 S8
- RBCs
- Brain (non-starvation)
What are the different types of glucose transporters, where are they found and what are their affinities?
L3 S10-11 LO1
GLUT1:
- found in all cells; especially high in RBCs and brain
- high affinity (Km: 1mM)
GLUT2:
- found in liver and pancreas
- low specificity (Km: 10mM)
GLUT3:
- found in neurons
- high affinity (Km: 1mM)
GLUT4:
- found in skeletal muscle, adipose tissue, and heart
- intermediate affinity (Km: 5mM)
- INSULIN REGULATED vesicle fusion
What is the net yield of glycolysis per molecule of glucose?
L3 S13 LO1
- 2 ATP
- 2 NADH
- 2 Pyruvate
What is the first phase of glycolysis and what occurs during it?
Investment
-use 2 ATP to trap glucose
Net reaction:
Glucose + 2 ATP -> fructose 1,6-BP
What does hexokinase do?
L3 S14 LO1
Converts glucose to glucose 6-P using ATP
Found in all cells
Inhibited by glucose-6P (feedback inhibition)
What does glucokinase do?
L3 S14 LO1
Converts glucose to glucose 6-P using ATP
Found only in the liver and pancreas
No feedback inhibition by glucose 6-P
What does phosphofructokinase do?
L3 S14
RATE LIMITING
Converts fructose 6-P to fructose. 1,6-BP
Inhibited by ATP and citrate
What is the second phase of glycolysis and what occurs during it?
L3 S15 LO1
Splitting
-goes from 1 6C molecule to 2 3C molecules
Net reaction:
-Fructose 1,6-BP -> 2 Glyceraldehyde 3-P
What does aldolase do?
L3 S15 LO1
Splits fructose 1,6-BP into DHAP and G3P
What does triose phosphate isomerase do?
L3 S15
Interconverts DHAP and G3P
G3P is used in next step of glycolysis
What is the third phase of glycolysis and what occurs during it?
L3 S16 LO1
Recoup/payoff
- 4ATP and 2NADH are generated
- pyruvate is generated
Net reaction:
-2 G3P + 4 ADP + 2 NAD+ -> 2 Pyruvate + 4 ATP + 2 NADH
What does glyceraldehyde 3-P dehydrogenase do?
L3 S16 LO1
Converts G3P to 1,3-BPG
Generates NADH
What does phosphoglycerate kinase do?
L3 S16 LO1
Converts 1,3-BPG to 3-phosphoglycerate
Generates ATP
What does pyruvate kinase do?
L3 S16 LO1
Converts phosphoenolpyruvate to pyruvate
Generate ATP
What are the regulated steps of glycolysis?
L3 S19 LO1
- hexokinase/glucokinase
- phosphofructokinase-1
- pyruvate kinase
How is hexokinase/glucokinase regulated?
L3 S20-21 LO1
Hexokinase is inhibited by G6P
Glucokinase is minimally affected by G6P
How is PFK-1 regulated?
L3 S22-23 LO1
Insulin actives phosphatases which activates PFK-2’s kinase activity and activates PFK-1
Glucagon activates PKA which activates PFK-2’s phosphorylase activity and inactivates PFK-1
What is Tarui disease?
L3 S24 LO1
GSD VII
Deficiency in PFK-1 (rate limiting enzyme of glycolysis)
How is pyruvate kinase regulated?
L3 S25 LO1
Activated by F1,6BP and insulin (activation of phosphatases)
Inhibited by ATP and glucagon (activation of PKA)
What are the possible fates of G6P?
L3 S27-28
- Glycolysis (pyruvate)
- Glycogen synthesis (glycogen)
- Pentosephosphate pathway (ribose)
How do defects in glycolysis affect RBCs?
L3 S31-32 LO1
Glycolysis is only means of ATP production for RBCs
Failure of glycolysis leads to hemolytic anemia.
What is Fanconi-Bickel syndrome?
L3 S37 LO1
Mutation in GLUT2 transporter (liver and pancreatic β cells
Results in inability to take up glucose efficiently in those cells
What steps of glycolysis must be bypassed in gluconeogenesis?
L3 S42 LO2
Hexokinase/glucokinase
-bypassed by glucose 6-phosphatase
Phosphofructokinase
-bypassed by fructose 1,6-bisphosphatase
Pyruvate kinase
-bypassed by PEP carboxylase and pyruvate carboxylase
What factors regulate glycolysis and gluconeogenesis?
L3 S44 LO2
High energy signals (ATP, glucagon) inhibit glycolysis and stimulate gluconeogenensis
Low energy signals (ADP/AMP, insulin) stimulate glycolysis and inhibit gluconeogenesis
What does pyruvate carboxylase do?
L3 S45 LO2
Converts pyruvate to oxaloacetate
What does malate dehydrogenase do?
L3 S46 LO46
Converts mitochondrial oxaloacetate into malate which can leave the mitochondria
Malate is converted back into oxaloacetate in the cytoplasm
What does phsophoenolpyruvate kinase do?
L3 S47 LO2
Converts oxaloacetate to PEP using GTP
What does fructose 1,6-bisphosphatase do?
L3 S47 LO2
RATE LIMITING
Converts fructose 1,6-bisphosphatase to
fructose 6-P
What does glucose 6-phosphatase do?
L3 S47 LO2
Dephosphorylates G6P to glucose
ONLY found in liver, kidneys, SI, and pancreas
What is GLUT7?
L3 S48 LO2
Removes glucose from the ER after being produced by glucose 6-phosphatase
What is the Cori cycle?
L2 S49 LO2
Links lactate production in muscles and RBCs to glucose production in liver
What is Von Gierke disease?
L3 S54 L2
GSD1a
Deficiency in glucose 6-phosphatase
Results in inefficient release of glucose from the liver and build of of stored glycogen in liver
What is the significance of fructose metabolism on glycolysis?
L3 S63 LO3
Fructose enters glycolysis as G3P, after rate limiting step. High consumption of fructose is linked to obesity because of this.
What is the significance of galactosemia?
L3 S65 LO3
Due to deficiency in galactose 1-P uridyltransferase (GALT) that results in accumulation of galactose.
Excess galactose is converted to galactitol which can accumulate in the eyes leading to cataracts
What is the rate limiting step of the PPP?
L3 S69-70 LO4
Glucose 6-phosphate dehydrognase
What is the first step of the PPP?
L3 S68 LO4
Oxidative phase
Contains rate limiting step
Produces NADPH and ribulose 6-phosphate
What is the second step of the PPP?
L3 S68 LO4
Non-oxidative
Products shunt to glycolysis/gluconeogenesis or nucleotide synthesis
What are the main products of PPP and what are they used for?
L3 S73 LO4
Ribose 5-P:
-used in nucleotide synthesis
NADPH:
-Used as a reducing agent in anabolic reactions
What are the non-reducing and reducing ends of glycogen?
L3 S75 LO5
Reducing:
- 1’ end
- connected to glycogenin
- does not grow
Non-reducing:
- 4’ end
- site for growth and shortening
What is phosphoglucomutase?
L3 S79 LO5
Converts glucose 6-P into glucose 1-P
What does UDP-glucose pyrophosphorylase do?
L3 S79 LO5
Converted glucose 1-P into UDP-glucose, the building block of glycogen
What does glycogen synthase do?
L3 S80 LO5
RATE LIMITING glycogen synthesis
Forms α-1,4 glycosidic bonds elongating glycogen
What does glucosyl 4:6 transferase do?
L3 S80 LO5
Takes roughly 7 glucose chain from glycogen and adds it onto the side of the chain via a 1,6 glycosidic bond
What does glycogen phosphorylase do?
L3 S82 LO5
RATE LIMITING glycogenolysis
Breaks glycogen from non-reducing end into glucose 1-P
What does debranching enzyme do?
L3 S83 LO5
Removes distal 3 of 4 remaining glucose of a branch and adds to end of chain
What does α-1,6-glucosidase do?
L3 S83 LO5
Cleaves last glucose of branch generating a glucose
How do fed and fasting states regulate glycogenesis and glycogenolysis?
L3 S87 LO5
Fed state:
- high insulin and glucose
- trigger dephosphorylation of glycogen synthase (activating) and glycogen phosphorylase (inactivating)
Starving state:
- high glucagon, low glucose
- triggers phosphorylation of glycogen synthase (inactivating) and glycogen phosphorylase (activating)
