Carb Metabolism I Flashcards
GLUT2
- hepatocytes and pancreatic cells
- responds to blood traveling through hepatic portal vein
- captures XS gluc for storage
- high Km ~15 mM and when it drops below this gluc bypasses liver and enters peripheral circulation
- serves as a glucose sensor for B-islet cells in pancreas for insulin release
GLUT4
- adipose tissue and muscle and respond to glucose concentration in peripheral blood
- insulin stimulates GLUT4 transporters to move towards membrane
- low Km ~5mM
- takes in XS gluc
how is XS gluc stored in muscle
glycogen
how is XS glucose stored in adipose tissue
DHAP to be turned into glycerol phosphate to store incoming FA as triacylglycerols
glycolysis general outline
- takes place in cytoplasm
- 1 gluc, 2 pyruvate
- 2 substrate level phosphorylations and 1 oxidation rxn
- produced e- carrier NADH to feed into aerobic respiration
- if glycolysis occurs anaerobically less energy
- produces intermediates for other pathways
- part of FA storage pathway
list the 6 important glycolysis enzymes and their roles
1) hexokinase (glucokinase in liver and B-islet): first step, attaches P group from ATP to gluc~>G6P thus trapping it inside, G6P inhibits hexokinase
2) PFK-1: inhibited by ATP and citrate, activated by AMP, F6P~>F1,6-BP, insulin stimulates, glucagon inhibits
3) PFK-2: insulin activates, converts F6P~>F2,6-BP thus activates PFK-1, but glucagon inhibits PFK-2 lowering this product and inhibits PFK-1
4) G3P dehydrogenase: oxidation and Pi addition to G3P forming 1,3-BPG and reduction of NAD+ to NADH
5) 3-PG kinase: 1,3-BPG + ADP~>ATP + 3-PG, high energy intermediate, substrate-level phosphorylation, not dependent on oxygen
6) pyruvate kinase: aerobic glycolysis only, SLP of ADP using PEP, activated by F1,6-BP from the PFK-1 rxn
fermentation
- will take place instead of glycolysis
- lactate dehydrogenase oxidizes NADH to NAD+ replenishing oxidized coenzyme for G3P dehydrogenase
- reduce pyruvate to lactate
- no net loss of carbon
- ensures all NAD+ isn’t used up
DHAP
- glycolysis intermediate
- hepatic and adipose tissues
- triacylglycerol synthesis
- formed from 1,6-BP then turned back into G3P then converted back to glycerol which is backbone of triacylglycerols
1,3-BPG and PEP
- glycolysis intermediates
- generate ATP by SLP
- high energy
- only ATP gained in anaerobic respiration
irreversible enzymes in glycolysis
gluco/hexokinase
PFK-1
pyruvate kinase
glycolysis in erythrocytes
- 2 ATP from 1 glucose
- BPH mutase 1,3-BPH~>2,3-BPG which binds allosterically to HbA and dec oxygen affinity to allow for unloading but still 100% saturation in lungs if not in XS
- allows transplacental oxygen passage from mother to fetus
galactose metabolism
- lactose hydrolyzed to galactose and glucose by lactase which is a brush border enzyme of small intestine
- reaches liver via hepatic portal vein
- phosphorylated by galactokinase trapping it as galactose 1-P~>G1P by galactose 1-P uridyltransferase and an epimerase
fructose metabolism
- sucrose hydrolyzed by brush border enzyme sucrase, fruc and gluc absorbed into HPV
- fructose phosphorylated using fructokinase to trap
- F 1-P~>glyceraldehyde + DHAP by aldolase
- produces products useful in glycolysis, glycogenesis, and gluconeogenesis
pyruvate dehydrogenase
- irreversible
- pyruvate~>acetyl CoA for TCA or FA synthesis
- liver activated by insulin
- needs cofactors: thiamine, pyrophosphate, lipoic acid, CoA, FAD, and NAD+
- inhibited by it’s product acetyl CoA (buildup of which happens during B-oxidation causing pyruvate to be made into OAA for gluconeogen)
glycogen
granules in cytoplasm w protein core
linear has highest density of glucose in core
branched has highest in periphery so that it can release gluc easier
glycogenesis
- synthesis of glycogen granules
- G6P~>G1P~UTP dephosphorylation~>UDP-gluc~UDP lost glycogen synthase used~>glycogen
- glycogen phosphorylase (epi, glucagon, AMP) can then add Pi to make G1P
what is the rate limiting enzyme of glycogenesis
- glycogen synthase
- a1,4glycosidic
- G6P & insulin activated
- Epi and glucagon phosphorylates and deactivates via protein kinase
branching enzyme
hydrolyzes a1,4 glycogen bond to move the glucs to make 1,6 bond
glycogen synthase then extends both branches
glycogenolysis rate limiting enzyme
breaks a1,4glycosidic bond of glycogen releasing G1P from periphery of granule
activated by glucagon in liver
activated by AMP and epi in skeletal muscle to signal need for more glucose
inhibited by ATP
debranching enzyme
glycogen
simply removes the glucoses nearest a a1,4 branch point and moves it to the end of the of another chain
hydrolyzes a1,6 bond releasing that single remaining gluc
gluconeogenesis
liver and kidney
promoted by glucagon and epi
inhibited by insulin
intermediates can be turned into glycolytic intermediates
important substrates for gluconeogenesis
- glycerol-3-P (stored from fats or triacylglycerols)
- lactate (anaerobic glycolysis)
- glucogenic aa (from muscle proteins except leucine and lysine)
is acetyl coa glucogenic
no
glucogenic substances
fructose and galactose in liver
FA w odd C # bc of propionyl-CoA
describe the 4 important enzymes of gluconeogenesis
1) pyruvate carboxylase: mitochondrial enzyme activated by acetyl-CoA from B-oxidation~>OAA TCA intermediate that can’t leave the mitochondria, OAA reduced to malate to get shuttled out
2) PEPCK: induced by glucagon and cortisol, converts OAA to PEP in rxn that requires GTP, PEP continues in the pathway to F1,6-BP, combo of this and pyruvate carboxylase circumvents effects of pyruvate kinase by converting pyruvate back to PEP
3) F1,6-bisphosphatase: rate limiting step, reverses action of of PFK-1, activated by ATP and inhibited by AMP and F2,6-BP
4) G6Pase: lumen of ER in liver cells, free glucose transported out into cytoplasm, absence in skeletal muscle means glycogen is for use within muscle only
pentose phosphate pathway
- cytoplasm of all cells
- produce NADPH and ribose 5-P for nucleotide synthesis
- rate limiting enzyme is G6PDase which is induced by insulin, inhibited by NADPH and activated by NADP+
- forms sugars that can feed back into glycolysis
- transketolase and transaldolase convert glycolytic intermediates into pentoses
NADPH
- electron donor
- potent reducing agent
- oxidized itself
