Metabolism Flashcards
name the 3 GLUT transporters
- GLUT1: blood-brain barrier, erythrocytes
- GLUT2: liver, pancreas b-islet cells, small intestine
- low affinity for glucose, bidirectional - GLUT4: muscle, adipose (insulin-regulated)
- exercise can induce expression
reaction and regulation of:
first irreversible step of glycolysis
glucose ==> glucose-6-phosphate
via hexokinase (muscle, adipose, RBC) or glucokinase (liver, pancreatic beta-cells)
hexokinase: not regulated by insulin, low Km and low Vmax
glucokinase: induced by insulin; inhibited by F6P and glucose; high Km and high Vmax
reaction and regulation of:
second irreversible step of glycolysis
rate-limiting step
fructose-6-phosphate ==> fructose 1,6-bisphosphate
via phosphofructokinase-1 (PFK-1)
inhibited by: ATP, citrate
activated by: AMP, fructose 2,6-bisphosphate
F2,6-bisphosphate is on/off switch for glycolysis
reaction and regulation of:
third (last) irreversible step of glycolysis
phosphoenolpyruvate (PEP) ==> pyruvate
via pyruvate kinase
inhibited by: ATP
activated by: AMP, fructose 1,6-bisphosphate
2 ATP generated
Cori cycle
glycolysis: glucose ==> pyruvate ==> lactate
gluconeogenesis: lactate ==> pyruvate ==> glucose
via lactate dehydrogenase
first irreversible reaction of gluconeogenesis
pyruvate ==> oxaloacetate
via pyruvate carboxylase
activated by: acetyl CoA (signals FA oxidation is taking place)
requires biotin as cofactor
this reaction also replenshes OAA for TCA cycle
second irreversible step of gluconeogenesis
oxaloacetate ==> phosphoenolpyruvate (PEP)
via phosphoenylpyruvate carboxykinase (PEPCK), rate-limiting step
cytosol (malate shuttle) and mitochondrial (lactate-pyruvate shuttle) PEPCK isozymes
inhibited by: insulin
activated by: glucagon
third irreversible step of gluconeogenesis
fructose-1,6-phosphate ==> fructose-6-phosphate
via fructose 1,6-bisphosphatase (FBP)
activated by: glucagon, low AMP, high ATP, low F26BP
fourth irreversible step of gluconeogenesis
glucose-6-phosphate ==> glucose
via glucose-6-phosphatase
only expressed in liver and kidney
inhibited by insulin
activated by glucagon
glycerol ==> glycerol-3-phosphate
product used in gluconeogenesis
catalyzed by glycerol kinase
hydrolysis of triacylglycerols ==> glycerol
other substrates for gluconeogenesis
besides pyruvate
- glycerol (TAGs hydrolysis)
- lactate (anaerobic glycolysis by muscle/RBCs)
- amino acids (glucogenic)
Cahill cycle
glucose-alanine cycle
liver: alanine ==> pyruvate ==> glucose
muscle: glucose ==> pyruvate ==> alanine
mechanism for:
alcoholic hypoglycemia
the metabolism of ethanol in the liver results in a massive increase in NADH
NADH drives pyruvate ==> lactate
by impairing the conversion of lactate to pyruvate, gluconeogenesis is impeded
irreversible step between glycolysis and TCA cycle
pyruvate ==> acetyl CoA
via pyruvate dehydrogenase complex (PDC)
deficiency in PDC causes lactate acidosis due to pyruvate being shunted to lactate; brain is particularly sensitive to acidosis
1st step of TCA cycle
irreversible step
acetyl CoA ==> citrate
via citrate synthase
citrate is an inhibitor of glycolysis
citrate can also be used for FA synthesis
2nd step of TCA cycle
reversible step
citrate ==> isocitrate
via aconitase
3rd step of TCA cycle
irreversible step
isocitrate ==> alpha-ketoglutarate
via isocitrate dehydrogenase
NAD+ ==> NADH
4th step of TCA cycle
irreversible step
alpha-ketoglutarate ==> succinyl CoA
via alpha-ketoglutarate dehydrogenase
NAD+ ==> NADH
5th step of TCA cycle
reversible
succinyl CoA ==> succinate
via succinate thiokinase
GDP ==> GTP
6th step of TCA cycle
reversible step
succinate ==> fumarate
via succinate dehydrogenase
FAD ==> FADH2
7th step of TCA cycle
reversible step
fumarate ==> malate
via fumarase
8th (final) step of TCA cycle
reversible step
malate ==> oxaloacetate
via malate dehydrogenase
NAD+ ==> NADH
irreversible steps of TCA cycle
3 steps
- acetyl CoA ==> citrate, via citrate synthase
- isocitrate ==> alpha-ketoglutarate, via isocitrate dehydrogenase
- alpha-ketoglutarate ==> succinyl CoA, via a-ketogluarate dehydrogenase
ATP-generating steps of TCA cycle
5 steps
- isocitrate dehydrogenase, NADH
- alpha-ketoglutarat dehydrogenase, NADH
- succinate thiokinase, GTP
- succinate dehydrogenase, FADH2
- malate dehydrogenase, NADH
mechanism behind
glycogen synthesis
glucose-6-phosphate ==> glucose-1-phosphate ==> …
glycogenin catalyzes addition of first glucose
glycogen synthase adds subsequent glucose molecules, creating a(1->4) bonds
branching enzyme adds a(1->6) bond to create branches
mechanism behind
glycogenolysis in lysosome
glycogen ==> glucose
via acid maltase (aka lysosomal a(1->4) glucosidase
where: heart, skeletal muscle, CNS
mechanism behind
glycogenolysis in liver
glycogen ==> glucose-1-phosphate
via glycogen phosphorylase, which cleaves a(1->4) bond
4-C branch ==> glucose + glucose-1-phosphate
via debranching enzyme
glucose-6-phosphate ==> glucose
via glucose-6-phosphatase (also last step in gluconeogenesis)
cellular locations of glycolysis, TCA cycle, gluconeogenesis, ETC
glycolysis: cytoplasm
TCA cycle: mitochondrial matrix
gluconeogenesis: cytoplasm
ETC: inner mitochondrial membrane
ETC complex I
“NADH dehydrogenase”
NADH goes to complex I and gets oxidized to NAD+; 2e- goes to coenzyme Q (coenzyme Q gets reduced)
ETC complex II
“succinate dehydrogenase”
FADH2 goes to complex II and gets oxidized to FAD; 2e- goes to coenzyme Q (coenzyme Q gets reduced)
ETC complex III
“cytochrome bc1”; “coenzyme Q-cytochrome c reductase”
2e- from coenzyme Q transferred to cytochrome c (cyt c gets reduced);
4H+ transferred to intermembrane space
ETC complex IV
“cytochrome c oxidase”
reduces O2 ==> H2O;
2H+ pumped into intermembrane space
ETC complex V
“ATP synthase”
ADP + Pi ==> ATP
2.5 ATP per NADH;
1.5 ATP per FADH2
Rotenone inhibits
ETC complex I (NADH dehydrogenase)
CoQ becomes oxidized
rotenone block can be bypassed by adding succinate
Antimycin a inhibits
ETC complex III (coQ-cytc reductase)
Complex I becomes reduced, cytochrome c becomes oxidized
antimycin a block can be bypassed by adding ascorbate (vitamin C), which provides e- through cytochrome c
Cyanide, CO, azide inhibit
ETC complex IV
all ETC components become reduced
ETC/ox-phos uncouplers
aspirin, DNP (2,4-Dinitrophenol), brown fat (thermogenin)
reduced proton gradient and increased oxygen consumption → electron transfer continues but ATP synthesis stops → production of heat
Oligomycin inhibits
ATP synthase
proton gradient becomes too steep for ETC to continue
fatty acid activation
FA ==> fatty acyl CoA
via **fatty acyl CoA synthetase **
LC fatty acyl CoA transport into mitochondria for oxidation requires carnitine shuttle
VLC fatty acyl CoA synthetase only found in peroxisomes
fatty acid beta-oxidation (even # chains)
fatty acyl CoA ==> acetyl CoA + remaining FA CoA chain (2 C less) + FADH2 + NADH
acetyl CoA goes to TCA cycle
fatty acid beta-oxidation (odd # chains)
propionyl CoA (3-C chain) ==> 4-C chain ==> succinyl CoA
via propionyl CoA carboxylase
fatty acid omega-oxidation
produces dicarboxylic cacids
occurs in endoplasmic reticulum
minor process that occurs more often when beta-oxidation is impeded
branched chain fatty acid alpha-oxidation
ex: phytanic acid (plants)
propionyl CoA ==> succinyl CoA ==> TCA cycle
ketone bodies
D-beta-hydroxybutyrate;
acetoacetate
ketone bodies ==> 2x acetyl CoA ==> TCA
