Flashcards in Carbohydrate Metabolism Deck (45):
Can glucose cross cell membrane, why?
No, it is too large and polar to be able to cross. It therefore requires the use of GLUTs (glucose transporters) that are located on the cell membrane or special case in a GLUT vesicle.
ubiquitous (found everywhere), high affinity (low Km) for glucose, used mainly in RBCs and brain. Facilitated diffusion.
Low affinity (high Km) for glucose, main transporter in liver. In a fed state, there is a surplus of glucose going through the liver, therefore the affinity of GLUT2 doesn't have to be that high. Facilitated diffusion
Main glucose transport in neurons, also has a high affinity (low Km) for glucose. Facilitated diffusion
Glucose transporter present in skeletal muscle, heart and adipose tissue. This transporter is INSULIN DEPENDENT/regulated by insulin. Facilitated diffusion. Found in vesicles within cytosol of cell. When insulin binds to a surface receptor, it signals the GLUT4 vesicle to fuse with the plasma membrane, now creating channels available for glucose uptake.
Fed state > Insulin released > GLUT4 binds to membrane > glucose uptake.
Transports glucose and fructose through the cell membranes. Facilitated diffusion
anaerobically: 2 pyruvate, 2 NADH, 2 ATP >> if continue 2 pyruvate are reduced to 2 lactate (muscle cells during exercise or red blood cells).
aerobically: pyruvate can be completely oxidized, or intermediates can go to other pathways.
three phases of glycolysis
1) investment: includes first three enzyme catalyzed reactions in glycolysis, uses 2 ATP.
2) Splitting: in two rxns the split of 1 6C molecule to 2 3C
3) Payoff: 4 ATP produced, 2 NADP produced.
What step of glycolysis traps glucose inside the cell
The first rxn in glycolysis phosphorylates glucose to G6P, which "traps" it inside the cell. All cells use HEXOKINASE to catalyze this rxn. The liver and pancreatic beta cells use GLUCOKINASE to catalyze this phosphorylation. This is a regulatory step
First regulatory step of glycolysis and what regulates it
The first regulatory step of glycolysis is the first rxn in glycolysis. Hexokinase or glucokinase use 1 ATP to phosphorylate glucose to G6P. G6P inhibit this step (feedback inhibition), Glucagon inhibits (excess glucose, stop making energy), Fructose 6-P inhibits, Glucose fructose 1-P and Insulin (fed state, make energy from food) activate this pathway. Hexokinase has high affinity for glucose, glucokinase has low affinity > mostly used after eating when glucose levels are elevated so affinity doesn't have to be very high
Enzymes with different structures, but the same function.
Rate limiting step of glycolysis, the enzyme of this step and regulators
The third rxn phosphorylates F6P to F1,6BP through the enzyme PHOSPHOFRUCTOKINASE-1. PFK-1 is positively regulated (continue through glycolysis) via AMP (more ATP needs to be generated -- hungry) and F2,6BP (product of side/parallel rxn) and high insulin/low glucagon (fed state). PFK is negatively regulated (slow/stop glycolysis) via ATP (have enough energy) or citrate (intermediate of TCA cycle).
glycolysis step that produces NADH
the 6th rxn of glycolysis converts G3P to 1,3BPG by using glyceralaldehyde 3-P dehydrogenase to reduce NAD+ to NADH (makes 2 NADH since theres 2 G3P).
Last regulatory step of glycolysis, enzyme and how it is regulated
The last rxn in glycolysis converts phosphoenolpyruvate (PEP) to pyruvate via PYRUVATE KINASE. Insulin and Fructose-1,6BP positively regulate PK (increase activity, has glucose, wants to make energy). Glucagon, ATP and ALANINE negatively regulate PK (has enough energy stored, slow glycolysis and PEP enters gluconeogenesis).
hexo: located everywhere, low Km, high affinity, low Vmax, glucose and other intermediates can be substrate, inhibited by G6P. glucokinase: located in liver and pancreatic beta, high Km, low affinity, high Vmax, glucose in the only substrate, not inhibited by G6P (but by glucagon)
Fed state ??????
and opposite is hungry (glucagon)
high insulin, stimulates protein phosphatase which dephosphorylates PK making it active allowing it to phosphorylate PEP to pyruvate.
G6P use in pathways other than glycolysis
Pentose phosphate pathway >> makes ribose for DNA/RNA and NADPH for those pathways, eventually used in galactose metabolism, glycogen synthesis
Pyruvate use in pathways other than glycolysis
transformed into oxaloacetate which is used in gluconeogenesis
converted to alanine for gluconeogenesis or protein synthesis
oxidized to acetly CoA and CO2 in TCA
reduced to lactate >> Cori cycle
glycolytic enzyme disorders often result in...
ineffective glycolysis = hemolytic anemia
Causes of type 2 diabetes
enzyme mutations, unable to convert proinsulin to insulin, defective insulin receptor, pancreatitis, pancreatic carcinoma
GSD VII: PFK-1 deficient > exercise induced muscle cramps/weakness, hemolytic anemia, jaundice,
creates glucose from carbohydrates (pyruvate) in liver, kidney and SI when blood glucose levels are low and glycogen stores are depleted. Not direct reversal of glycolysis. Uses lactate, AA and glycerol as precursors. Bypasses irreversible steps of glycolysis using different enzymes.
Would chose to breakdown 1) glycogen stores/lactate/other carbs(galactose/fructose) 2) fat/glycerol 3) proteins/alanine
glycolysis vs gluconeogenesis
gluconeogenesis uses: pyruvate carboxylase (PC), phosphoenolpyruvate carboxylkinase (PEPCK), F1,6BPhatase, G6Phatase
PC enzyme gluconeogenesis
converts pyruvate to oxaloacetate so it can pass from inner mitochondrial space to cytosol. it is found on mito membrane. OAA is converted to malate in mito, malate transferred through the membrane via malate shuttle and reoxidized to OAA in cytosol. Pyruvate carboxylase uses biotin cofactor.
Rate determining step of gluconeogenesis
converting F1,6BP to fructose 6P via FRUCTOSE 1,6-BISPHOSPHATASE. this enzyme is activated by cortisol and citrate (TCA intermediate). Inhibited by AMP and F26BP
Glucose 6-phosphatase location and function
Located on lumen of ER, the G6Ptase converts G6P to glucose. G6P transported into ER and converted to glucose which is then transported into cytosol by GLUT 7
on ER lumen and transports glucose from lumen into cytosol in final step of gluconeogenesis
in RBC and exercising muscle: moves lactate (produced by anaerobic glycolysis) into blood supply and then into liver for gluconeogenesis
Fructose-1,6-bisphosphatase deficiency and its results on gluconeogenesis
similar to Tarui, but for gluconeogenesis. presents infancy. hypoglycemia, lactic acidosis, ketosis, apnea
Von Gierke disease
GSD1a: glucose 6 phosphatase deficiency = can't take final phosphate of of G6P in gluconeogenesis so unable to produce free glucose. Hepatomegaly, lyperlipidemia,
GLUT 2 mutation
Fanconi-Bickel syndrome: can't uptake glucose, fructose or galactose. Autosomal recessive disorder leads to hepatomegaly, resistant rickets. Treated with a special diet.
converts glucose to fructose via sorbitol intermediate. Cells without sorbitol dehydrogenase will accumulate sorbitol >> water influx >> swelling >> cataracts
Doesn't rely on PFK-1 so the rate determining step of glycolysis is skipped >> faster metabolism >> easier converted into fat >> less healthy
GALT (glucose 1P uridyltransferase) is the rate limiting step
glucose 1P uridyltransferase: galactitol accumulates >> liver failure/sepsis/bleding
PPP (pentose phosphate pathway)
the purpose is to create ribose used in DNR/RNA and NADPH used for biosynthesis. occurs in cytosol. Has an oxidative and nonoxidative phase.
Oxidative: G6P dehydrogenase (RATE LIMITING STEP) G6PD deficiency results in hemolytic anemia
non-oxidative: ribose is creates from ribulose and an isomerase. other glycolysis/gluconeogenesis metabolites are also created. Reversible reactions.
What is glycogen
large glucose storage molecules when excess glucose in in body. has a 1,4 glycosidic bonds between linear sections and a1,6 glycosidic bonds at branch points. connected to a protein primer/glycogenin at the reducing end. non-reducing ends are added glucose at C4-OH
where is glycogen stored
in the liver and muscle as granules (enzymes necessary + glycogen)
liver glycogen regulates BLOOD glucose
Muscle glycogen provides fuel for physical activity
process of making and extending glycogen molecules from glucose units.
glucose still trapped in cell by phosphorylating to G6P > G1P > UDP-glucose
rate determining step of glycogenesis
GLYCOGEN SYNTHASE transfers glucose from UDP-glucose to the non-reducing (4C-OH of glucose) by forming a1,4 glycosidic bond
How does glycogen branch
GLYCOSYL 4:6 TRANSFERASE breaks linear 11 glucose chain and attaches a 7 glucose chain to the 4th glucose away from previous branch or core protein.
Rate limiting step is GLYCOGEN PHOSPHORYLASE which cleaves glucose residues until within 4 glucoses from branch point.
the Debranching enzyme releases the glucoses of the branch until the last one until glucosidase cuts the final glucose off the branch leaving a new linear glycogen chain to be degraded by GLYCOGEN PHOSPHORYLASE
regulation of Glycogen Synthase
dephosphorylated is the active form and phosphorylated is the inactive form