glycolysis Flashcards
glycolysis involves a sequence of reactions that metabolizes:
1 molecule of glucose to 2 molecules of pyruvate and generates 2 molecules of ATP
under aerobic conditions, pyruvate is
completely oxidized generating much more ATP
aerobic system is more efficient than anaerobic
complete oxidation is more energy efficient than
anaerobic glycolysis
sources of glucose in diet:
disaccharides (especially sucrose and lactose)
starch
glycogen
in mammals:
glucose is the only fuel that brain uses under
glucose is the only fuel that ______ cells can use
conditions of non-starvation
red blood
pyruvate and lactate can be salvaged and resynthesized to glucose via
gluconeogenesis
glucose uptake occurs via protein transporters called
glucose transporters (GLUTs)
GLUT 1
ubiquitous but expressed highly in brain, RBCs, cornea, placenta, and cancer cells
high affinity
unregulated
GLUT 2
main transporter in liver (also pancreas)
low affinity
unregulated
GLUT 3
main transporter in neurons
high affinity
unregulated
GLUT 4
present in skeletal muscle, heart, and adipose tissue
insulin dependent
largest GLUT transporter
GLUT 2
smallest GLUT transporter
GLUT 1/3
location of glycolysis
occurs in cytoplasm of eukaryotic cells
two stages of glycolysis
1.
2.
- trapping of glucose and its cleavage into 2 interconvertible 3-carbon molecules
- generation of ATP
first stage of glycolysis begins with:
ends with
the phosphorylation of glucose
the isomerization of dihydroxyacetone phosphate to glyceraldehyde 3-phosphate (GAP)
trapping of glucose (through GLUTs) and preparation phase:
ATPs consumed:
ATPs generated:
2 ATPs consumed
no ATPs generated
strategy of stage 1 is to:
and form a compound that can be readily cleaved into:
trap the glucose in the cell
2 phosphorylated 3-carbon units
stage 1 step 1
ATP:
enzyme:
glucose phosphorylated to glucose-6-phosphate (G6P)
ATP is consumed
enzyme: hexokinase (in all tissues) and glucokinase (in liver)
stage 1 step 2
ATP:
enzyme:
G6P isomerized to fructose-6-phosphate (F6P)
no ATP
enzyme: phosphoglucoisomerase
stage 1 step 3
ATP:
enzyme:
F6P phosphorylated to fructose-1,6-bisphosphate (F1,6BP)
ATP is consumed
enzyme: phosphofructokinase (rate limiting enzyme of glycolysis)
stage 1 step 4
ATP:
enzyme:
F1,6BP broken down to glyceraldehyde-3-phosphate (G3P/GAP) and dihydroxyacetone phosphate (DHAP)
no ATP
enzyme: aldolase
stage 1 step 5
ATP
enzyme:
DHAP isomerized to G3P (GAP)
no ATP
enzyme: triose phosphate isomerase
second stage of glycolysis:
energy harnessed in _____ used to form _____
GAP
ATP
stage 2 step 1
NAD+
enzyme:
oxidative phosphorylation of GAP to form 1,3-bisphosphoglycerate (1,3-BPG)
NAD+ reduced to NADH
enzyme: glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
NADH contains
a pair of “high energy” electrons
sent to ETC, plays role in oxidative phosphorylation
stage 2 step 2
ATP:
enzyme:
1,3 BPG is converted to 3-phosphoglycerate (3-PG)
ADP is phosphorylated to form ATP
enzyme: phosphoglycerate kinase
stage 2 step 3
ATP
enzyme:
3-PG is converted to 2-phosphoglycerate (2-PG)
no ATP
enzyme: phosphoglycerate mutase
stage 2 step 4
water:
enzyme:
2-PG is dehydrated to form phosphoenolpyruvate (PEP)
water is formed
enzyme: enolase
stage 2 step 5
ATP:
enzyme:
PEP is converted from unstable enol to pyruvate, a stable ketone
ATP is formed
enzyme: pyruvate kinase
this step is irreversible
pyruvate can be reduced to
lactate, with the generation of NAD+
pyruvate can be oxidized aerobically via the
citric acid cycle after first undergoing an oxidative decarboxylation to form acetyl CoA and producing CO2
yeast and some other microorganisms can convert pyruvate to
ethanol
fermentation
pyruvate –> lactate produces NAD+ that can be used in what step of glycolysis?
GAP –> 1,3 BPG
sucrose is a disaccharide of
glucose and fructose
lactose is a disaccharide of
glucose and galactose
fructose and galactose can be converted into
glycolytic intermediates
fructose quickly turned into ______ in times of high energy
fat
what is important about fructose metabolism?
it bypasses the rate limiting step of glycolysis
fructose metabolism:
- fructose –> fructose 1-phosphate via enzyme fructoskinase (ATP –> ADP)
- fructose 1-phosphate –> glyceraldehyde + DHAP via enzyme fructose 1-phosphate aldolase
- glyceraldehyde –> G3P/GAP via enzyme triose kinase
galactose metabolism
- galactose –> galactose 1-phosphate via galactokinase
- galactose 1-phosphate + UDP-glucose –> glucose 1-phosphate via enzyme: galactose 1-phosphate uridyl transferase
- glucose 1-phosphate –> glucose 6-phosphate via phosphoglucomutase
major regulatory enzymes of glycolysis and reactions they catalyze
hexokinase: glucose –> glucose 6-phosphate (ATP –> ADP)
phosphofructokinase (rate-limiting step): fructose 6-phosphate –> fructose 1,6 bisphosphate (ATP –> ADP)
pyruvate kinase: phosphoenolpyruvate –> pyruvate (ADP –> ATP)
glycolysis in at rest muscles (major regulatory enzymes)
glycolysis is inhibited
glucose 6-phosphate inhibits action of hexokinase
high ATP : AMP ratio inhibits PFK and PK
glycolysis in muscles during exercise (major regulatory enzymes)
glycolysis is stimulated
glucose 6-phosphate is continuing on in pathway (does not inhibit hexokinase)
low ATP : AMP ratio activates PFK and PK
goal of glycolysis in muscle
to generate ATP during activity (ATP levels regulate glycolysis)
goals of glycolysis in liver
to maintain blood glucose levels
to provide building blocks for other pathways
glycolysis in liver (major regulatory enzymes)
glucokinase is not inhibited by glucose 6-phosphate (glucose is permanently trapped)
(very little hexokinase in live)
PFK is activated by F-2,6-BP (inhibited by citrate)
PK is regulated by allosteric effectors and covalent modifications (F-1,6-BP activates and ATP inhibits)
hexokinase has a ______ affinity for glucose
high
glucokinase has a ______ affinity for glucose
low
excessive fructose has been linked to
fatty liver, insulin insensitivity, obesity, type II diabetes
actions of fructokinase and triose kinase bypass
hte most important regulatory step in glycolysis (PFK rate limiting step)
fructose-derived G3P and DHAP are processed by
glycolysis to pyruvate and acetyl CoA in an unregulated fashion
excess acetyl CoA (from excess fructose) is converted to
fatty acids which can be transported to adipose tissue to form triacylglycerols, resulting in obesity ; and liver also begins to accumulate fatty acids resulting in fatty liver
activity of fructokinase and triose kinase (from fructose consumption) can deplete the liver of
ATP and inorganic phosphate, compromising liver function
lactose intolerance
inability to metabolize lactose
drinking milk causes disturbances in GI function
lactose intolerance is caused by
deficiency in enzyme lactase (which breaks down lactose to glucose and galactose)
galactosemia
disruption of galactose metabolism
classic galactosemia (most common form)
is an inherited deficiency in galactose 1-phosphate uridyl transferase activity
defects in galactose metabolism results in:
failure to thrive
vomiting/diarrhea after consuming milk
enlargement of liver and jaundice
cataracts
lethargy and retarded mental development
significant elevation of blood-galactose levels and presence of galactose in urine
how do you diagnose defect in galactose metabolism
absence of galactose 1-phosphate uridyl transferase in RBCs
how to you treat defect in galactose metabolism
remove galatose (and lactose) from diet
although elimination of galactose from diet (in patients with defect in galactose metabolism) prevents liver disease and cataract development, many patients still suffer from
CNS malfunction, most commonly a delayed acquisition of language skills
cataracts results from
galactose being unable to enter glycolysis and instead being turned into galactitol
warburg effect (aerobic glycolysis)
rapidly growing tumor cells metabolize glucose to lactate even in the presence of oxygen
visualization of tumor and effectiveness of treatment:
a non-metabolizable glucose analog, 2-F-2-D-deoxyglucose detected by a combination of
positron emission tomography (PET) and computer-aided tomography (CAT)
