Carbohydrate Metabolism Flashcards
Purpose of glycolysis
- metabolize 1 molecule of glucose to 2 molecules pyruvate
- generate 2 molecules ATP
- Anaerobic process
- fructose, galactose, and other sugars can also be used
Glycolysis location
the cytoplasm of all cell types - usually a precursor rxn
- RBC do not have mitochondria, so they rely solely on glycolysis
- glucose is the only fuel the brain uses under non-starvation conditions
Carbohydrate sources in diet
- monosaccharides (glucose, fructose, galactose)
- disaccharides - sucrose (gluc+fruc) and lactose (gluc+galac)
- polysaccharides - starches (from plants) and glycogen (animals)
- De novo synthesis (gluconeogenesis in liver)
Glucose transporters
GLUT1-4
GLUT1: all cell types (esp brain and RBC, high affinity)
GLUT2: Liver (low affinity-all digested nutrients go to liver first so it doesn’t need high affinity)
GLUT3: Main transporter in neurons (high affinity)
GLUT4: Skeletal muscle, heart, and adipose tissue (INSULIN DEPENDENT)
GLUT4
Insulin dependent glucose transporter
- GLUT4 is sequestered in vesicles
- when insulin binds, it signals for vesicles to fuse with membrane, incorporating GLUT4 and allowing more glucose to enter cell for glycolysis
Km
inversely proportional to the affinity (high affinity = low Km and vice versa)
3 phases of glycolysis
Investment (uses 2 ATP at different steps)
Splitting (6-C molecule splits into 2x 3C molecules)
Recoup/Payoff (4 ATP molecules formed - NET: 2 ATP, 2 NADH, 2 pyruvate)
Investment phase
- phosphorylation of glucose to G6P
- Regulatory step of glycolysis - traps glucose in the cell - uses ATP
- Enzymes (hexokinase-all cells, glucokinase-liver and pancreatic B cells) - Isomerization of G6P to F6P (by phosphoglucose isomerase)
- Phosphorylation of F6P to fructose 1,6-bisphosphate (F1,6BP) **Rate limiting step
Rate limiting step of glycolysis
phosphorylation of F6P to fructose 1,6-bisphosphate
Enzyme: PFK1 (phosphofructokinase 1)
Hexokinase
investement phase of glycolysis - phosphorylates glucose to glucose-6-phosphate
- uses 1 ATP
- inhibited by glucose-6-phosphate (neg. feedback mech)
ALL CELL TYPES
Glucokinase
- phosphorylates glucose to G6P - in liver and pancreatic B cells
- uses 1 ATP
- propelled by: glucose, fructose 1-p, insulin
- inhibited by: glucagon, Fructose 6-P (next step in pathway)
Phosphofructokinase-1
- phosphorylates F6P to fructose 1,6-bisphosphate (F1,6BP)
- uses 1 ATP
- rate limiting step of glycolysis
- propelled by: AMP, Fructose 2,6BP
- inhibited by: ATP (don’t need more), Citrate
Aldose A
Cleaves F1,6BP to 2x 3C molecules
- DHAP and G3P
- then triose phosphate isomerase favors G3P –> 2 G3P
Glyceraldehyde 3P dehydrogenase (GAPDH)
phosphorylates G3P
- Yields 2 NADH
produces 1,3BPG
Phosphoglycerate Kinase
converts 1,3BPG to 3PG
Yields 2ATP
Pyruvate Kinase
forms pyruvate
Yields 2ATP
Irreversible step
3 irreversible steps glycolysis
Catalysts: Hexokinase/glucokinase (gluc to G6P), phosphofructokinase 1 (makes bisphosphate, rate limiting step), pyruvate kinase (makes pyruvate) Activity Influenced by: -ATP/AMP (energy status) -glucose (feeding status) -insulin and glucagon (hormone status)
Daddy molecules
insulin and glucagon
- insulin stimulates a phosphatase (removes P), fed
- glucagon stimulates a kinase (phosphorylates), fasting
Tarui disease
- deficiency in PFK-1
* PFK-1 catalyzes rate limiting step of Glycolysis, so deficiency means that glycolysis is decreased
Glucose-6 phosphate
precursor for pentose phosphate pathway
- also used in galactose metabolism, glycogen synthesis, uronic acid pathway
Regulation of glycolysis during exercise
during exercise - ATP is decreased, slightly more AMP, which stimulates PFK1 –> makes bisphosphate at a higher rate which stimulates pyruvate kinase –> makes pyruvate (either makes CO2 + H2O moderate exercise or lactate in a sprint)
- this would be during muscle fiber contraction, glycolysis activated to meet energy requirements
Disorders of glycolysis
most result with hemolytic anemia, because RBC need glycolysis for energy.
Type 1 Diabetes
hyperglycemia (glycolysis disorder)
loss of pancreatic B cells (likely from immune destruction) causes severe insulin deficiency (GLUT4 not signaled into PM and glucose does not get in cell, stays in blood)
- some potential causes include mutations in GK, mitochondiral tRNA genes, averrant conversion of proinsulin to mature insulin, defective insulin receptor, pancreatitis, pancreatic carcinoma, trauma, infection, etc
Type 2 diabetes
hyperglycemia (glycolysis disorder)
- insulin resistance that progresses to loss of B cell function
- (GLUT4 not signaled into PM and glucose does not get in cell, stays in blood)
- insulin not activating pathway/signaling cascade for glycogen synthesis
- some potential causes include mutations in GK, mitochondiral tRNA genes, averrant conversion of proinsulin to mature insulin, defective insulin receptor, pancreatitis, pancreatic carcinoma, trauma, infection, etc
Hemolytic Anemia
premature destruction of RBCs (glycolysis disorder)
- clinical markers - elevated lactate dehydrogenase, unconjugated bilirubin
- accumulation of intracellular Na causes swelling and lysis cell death
Fanconi-Bickel syndrome
autosomal recessive (glycolysis disorder)
- mutation in GLUT2 transporter (liver, pancreatic V cell)
- unable to take up glucose, fructose, and galactose
- hepatomegaly, tubular nephropathy, abdominal bloating, resistant rickets
Gluconeogenesis
- synthesis of new glucose from different sources (can be carbohydrate sources or non-carbohydrate sources)
- occurs in liver, kidneys, and small intestine (not every cell type)
- not a reversal of glycolysis