L10: Glycolysis Flashcards
lactose composed of
- galactose
- glucose
sucrose composed of
- glucose
- fructose
where are starches degraded?
- salivary amylase in mouth first
- pancreatic amylase in small intestine
small saccharides are degraded by
- glycosidases attached to the intestine
- sucrase, lactase
what happens to sugars like glucose, galactose, and fructose?
- transported into intestinal cells
- then exported into the circulation
GLUT 1
- present in most cell types, including fetal tissues
- responsible for basal glucose transport in most cell types
- Km lower than normal glucose levels
- all cells can efficiently extract glucose from serum
GLUT 2
- present in liver and pancreatic beta cells
- transports only when glucose levels are high
- Km is high
- bidirectional transporter in liver
what does the liver usually use for energy?
- fatty acid breakdown
GLUT 3
- present mostly in neurons and the placenta
GLUT 4
- present in muscle and fat cells
- the number of transporters increases in presence of insulin
- promotes ability of tissues like muscle to get glucose
is glucose anaerobic or aerobic?
- facultatively anaerobic
- can run in presence or absence of oxygen
where does glycolysis occur?
- cytoplasm
step 1 of glycolosis
- glucose -> glucose-6-phosphate
- via hexokinase
- requires ATP
- traps glucose in the cell because G-6-P cannot pass through membrane due to negative charge of phosphate tail
step 2 of glycolysis
- glucose-6-phosphate -> fructose-6-phosphate
- via phosphoglucose isomerase
step 3 of glycolysis
- fructose-6-phosphate -> frucose-1,6-bisphosphate
- via PFK-1
- requires ATP
step 4 of glycolysis
- fructose-1,6-bisphosphate -> glyceraldehyde-3-phosphate and DHAP
- via aldolase
step 5 of glycolysis
- DHAP -> glyceraldehyde-3-phosphate
- via triode phosphate isomerase
- GAP can generate ATP but DHAP cannot
step 6 of glycolysis
- GAP -> 1,3-bisphosphoglycerate
- via glyceraldehyde-3-phosphate dehydrogenase
- NAD+ reduced to NADH
step 7 of glycolysis
- 1,3-bisphosphoglycerate -> 3-phosphoglycerate
- via phosphoglcyerate kinase
- ATP is formed
step 8 of glycolysis
- 3-phosphoglycerate -> 2-phosphoglycerate
- via phosphoglyceromutase
NAD+ derived from
- niacin or vitamin B3
FAD derived from
- riboflavin or vitamin B2
step 1 of fructose metabolism
- fructose -> fructose-1-P
- by fructokinase
- requires ATP
step 2 of fructose metabolism
- fructose-1-P -> glyceraldehyde and DHAP
- via aldolase B
step 3 of fructose metabolism
- glyceraldehyde -> glyceraldehyde-3-phosphate
- via triose kinase
- uses ATP
fructose intolerance cause
- defect in aldolase B
result of fructose intolerance
- fructose-1-phosphate accumulates in liver and kidney and cannot exit cell
- depletes ATP pools since utilization of fructokinase requires ATP
- also inhibits glycogen phosphorylase and glycogen breakdown
reductions in aldolase B result in
- decreased glucose
symptoms of fructose intolerance
- lactic acidosis
- hypoglycemia
- nausea
- convulsions
- jaundice
- symptoms get worse with ingestion of honey, juice, fruit
cause of essential fructosuria
- defect in fructokinase
symptoms of fructosuria
- asymptomatic
- can compensate in other ways
result of fructosuria
- no accumulation of fructose in cells, since it can exit cell
- unlike fructose-1-phosphate
function of lactase
- cleaves galactose from lactose
where do we get most of our galactose?
- from dairy products in the form of lactose
galactose metabolism overview
- galactose broken down into glucose
- uses ATP
classical galactosemia cause
- defect in galactose-1-phosphate uridyltransferase
- second step of galactose metabolism
classical galactosemia result
- accumulate galactose-1-phosphate and galactose
classical galactosemia symptoms
- intellectual disability
- cataracts
- liver disease
classical galactosemia treatment
- reduce lactose consumption
nonclassical galactosemia cause
- defect in galactokinase
non classical galactosemia result
- accumulates galactose only
non classical galactosemia symptoms
- mild
- cataracts
low levels of lactase
- or intestinal injury
- result in abdominal pain, bloating, nausea, flatulence, and diarrhea when consuming lactose-containing products
western Northern Europeans and tribes of subsaharan Africa
- maintain high levels of lactase as adults
- lactose tolerant
congenital lactase deficiency
- rare
- results in severe lactose intolerance in adults
NAD+ regeneration under hypoxic conditions
- pyruvate can oxidize NADH to produce lactate and NAD+
- via lactate dehydrogenase
- unable to form acetyl CoA and generate energy
- results in reduced blood pH and lactic acidosis
- glycolysis still sustained because you donโt have a buildup of pyruvate
NAD+ regeneration under normoxic conditions
- shuttle systems used for transferring reducing equivalents between cytoplasm and mitochondria
chronic alcoholism
- buildup of NADH
- pyruvate will go into lactate instead of TCA
- why alcoholics are often lethargic
cori cycle
- glucose produced in liver taken up by other cells and is converted to lactate and released back into the blood
- lactate taken up and converted back to glucose through gluconeogenesis
glycerol-3-phosphate shuttle
- cytoplasmic glycerol 3-P dehydrogenase transfers electrons from NADH to DHAP โ glycerol 3-P and NAD+
- Glycerol 3-P diffuses into the mitochondrial membrane where a mitochondrial glycerol 3-P dehydrogenase donates the electrons to FAD to form FADH2
- CoQ accepts electrons from FADH2 during oxidative phosphorylation
malate aspartate shuttle
- Cytosolic malate dehydrogenase transfers electrons from NADH to oxaloacetate to form malate
- Occurs in the cytosol
- Regenerates NAD+
- Malate is transferred across mitochondrial membrane in exchange for ๐ผ-ketoglutarate being transported into the cytosol
- In the mitochondria, malate is oxidized to oxaloacetate, generating NADH โ donates electrons for oxidative phosphorylation
- Oxaloacetate is transaminated (TA) to aspartate, which is transported to the cytoplasm and transaminated back to oxaloacetate
inhibition of hexokinase
- inhibited by glucose-6-phosphate
inhibition of PFK-1
- inhibited by high levels of ATP (binds at regulatory site)
- inhibited by citrate from TCA cycle, and low pH
- makes sense because these are both products
stimulation of PFK-1
- stimulated by AMP
- stimulation by fructose-2,6-bisphosphate
- AMP indicates low energy status so need more glycolysis
regulation of the cycle by fructose-2,6-phosphate
- stimulates PFK-1 when glucose levels are high
- inhibits fructose-1,6-bisphosphatase
insulin secreted by
- pancreatic beta cells
- in response to high glucose
- insulin receptor binding triggers signal transduction cascade
glucagon secreted by
- pancreatic alpha cells and epinephrine
- binding to GCPRs stimulates a protein kinase A signal transduction pathway
regulation of fructose-2,6-bisphosphate
- regulated by PFK-2
- kinase
- phosphatase
PFK-2 kinase
- phosphorylates F-6-P to form F-2,6-BP
- stimulates glycolysis
PFK2 phosphatase
- dephosphorylates F-2,6-BP to form F-6-P
- inhibits glycolysis
high glucose levels, insulin, PFK2
- glucose high
- insulin activates phosphoprotein phosphatase
- removes phosphate from PFK2 kinase domain
- increases F-2,6-BP from F-6-P -> glycolysis predominates
pyruvate kinase inhibition
- inhibition by ATP (allosterically)
- inhibited by glucagon
- results in phosphorylation of pyruvate kinase, reducing it
pyruvate kinase stimulation
- stimulated by F-1-6-BP
- insulin stimulates phosphatases dephosphoryate PK and it becomes more active
mature red blood cells
- require glycolysis for ATP
- cannot do anything else
genetic reduction of pyruvate kinase activity
- glycolytic enzyme mutation
- results in death and lysis of red blood cells
- anemia
- tissues with mitochondria are okay because they can generate ATP by oxidative phosphorylation
step 9 of glycolysis
- 2-phosphoglycerate -> phosphoenolpyruvate
- via enolase
step 10 of glycolysis
- phosphoenolpyruvate -> pyruvate
- via pyruvate kinase
