GLUT 2: low-affinity in hepatocytes and pancreatic cells (high Km) ; fx only when glucose concentrations are high
GLUT 4: adipose and mscle; rate of glucose transport increased by insulin; Km is lower; responds when glucose just a tad above normal
Muscle stores excess glucose as __, and adipose tissue requires glucose to form __, which is converted to glycerol phosphate to store incoming fatty acids as __
gycogen
DHAP
triacylglycerols
In the liver, glycolysis is part of the process by which __
excess glucose is converted to fatty acids for storage
hexokinase and glucokinase
phosphorylate glucose to trap it in the cell
hexokinase
low Km
inhibited by glucose-6-phosphate
glucokiase
high Km
located in hepatocytes and pancreatic beta-islet cells
induced by insulin
Phosphofructokinase-1
rate-limiting enzyme
fructose-6-phosphate is phosphorylated to fructose 1,6-bisphosphate
inhibited by: ATP and citrate; glucagon
activated by: cAMP; insulin
Insulin activates __, which converts a tiny amount of __ to __, which activates __.
PFK-2
fructose-6-phosphate
fructose-2,6-bisphosphate
PFK-1
Glucagon inhibits __, lowering __ and thereby inhibiting __.
PFK-2
F2,6-BP
PFK-1
By activating __, it allows these cells to override the inhibition caused by ATP so that glycolysis can continue, even when the cell is energetically satisfied.
PFK-1
Gylceraldehyde-3-phosphate dehydrogenase
catalyzes an oxidation and addition of inorganic phosphate to its substrate, glyceraldehyde 3-phosphate, which results in production of a high energy intermediate 1,3-bisphosphoglycerate and reduction of NAD+ to NADH
3-phosphoglycerate kinase
transfers phosphate from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate
Pyruvate kinase
catalyzes the substrate-level phosphorylation of ADP using the high-energy substrate PEP
activated by fructose 1, 6-bisphosphate from PFK-1 reaction
Key fermentation enzyme in mammals
lactate dehydrogenase (oxidizes NADH to NAD+)
DHAP
used in hepatic and adipose for triacylglycerol synthesis
can be isomerized to glycerol 3-phosphate
1,3-bisphosphoglycerate and phosphoenolpyruvate
high-energy intermediates used to generate ATP by substrate-level phosphorylation
Irreversible enzymes
Glucokinase
hexokinase
PFK1
pyruvate kinase
Red blood cell glycolysis
uses bisphosphoglycerate mutase, which produces 2,3-bisphosphoglycerate (2,3-BPG) from 1,3-BPG
adapatations to high altitudes (low pO2)
increased respiration
increased oxygen affinity for hemoglobin
increased rate of glycolysis
increased [2,3-BPG] in RBC (over a 12-24 hour period)
normalized oxygen affinity for hemoglobin restored by increased level of 2,3-BPG
increased hemoglobin (over days to weeks)
How can galactose enter the pathway?
Phosphorylated to galactokinase, trapping it in cell.
The resulting galactose 1-phosphate is converted to glucose 1-phosphate by galactose-1-phosphate uridyltransferase and an epimerase
How does fructose enter the pathway?
fructose converted to frucose 1-phosphate by fructokinase. Then, glyceraldehyde and DHAP convert it to aldolase B.
PDH complex
irreversible
cannot convert acetyl-CoA to pyruvate or to glucose
activated by insulin (liver)
Three fates of pyruvate
1) conversion to acetyl-CoA by PDH
2) coversion to lactate by lactate dehydrogenase
3) Conversion to oxaloacetate by pyruvate carboxylase
Explain glycogen granules.
central protein core with polyglucose chains radiating outward to form a sphere
composed entirely of linear chains and have the highest density of glucose near the core
branched chains are more dense at periphery, allowing more rapid release of glucose on demand
Glycogenesis
synthesis of glycogen granules
begins with core protein glycogenin and glucose addition begines with glucose 6-phosphate, which is converted to glucose 1-phosphate
uridine diphosphate permits integration into glycogen chain by glycogen synthase
glycogen synthase
rate limiting enzyme of glycogen synthesis and forms alpha-1,4 glycosidic bond found in linear glucose chains of the granule
glycogen synthase is stimulated and inhibited by __
stimulated by glucose 6-phosphate and insulin
inhibited by epinephrine and glucagon
Branching enzyme
introduces alpha-1,6-linked branches into the ranule
hydrolyzes one alpha-1,4-bonds to release oligoglucose
breaks alpha-1,4 bond adjacent to the branch point and moves the small oligoglucose chain that is released to teh exposed end of the other chain
form a new alpha-1,4-bond
hydrolyzes the alpha-1,6-bond, releasing the single residue at the branch point as free glucose
Gluconeogenesis
the production of glucose from other biomolecules; carried out by the liver and kidney
The liver maintains glucose levels in blood during fasting through either __ or __.
glycogenolysis
gluconeogenesis
Gluconeogenesis or glycogenolysis stimulated or inhibited by...?
stimulated by glucagon and epinephrine
inhibited by insulin
During fasting, what happens?
glycogen reserves drop dramatically in the first 12 hours, during which time gluconeogenesis increases. After 24 hours, it represents the sole source of glucose
Important substrates for gluconeogenesis are
glycerol 3-phosphate
lactate
glucogeneic amino acids
glucogenic amino acids
can be converted into intermediates that feed into gluconeogenesis
ketogenic amino acids
converted into ketone bodies, which can be converted into alternative fuel, particularly during periods of prolonged starvation
True or False:
It is possible to convert acetyl-CoA back to glucose
False: it is not
Lactate is converted to pyruvate by __. Alanine is converted to pyruvate by __. Glycerol 3-phosphate is converted to DHAP by __
lactate dehydrogenase
alanine aminotransferase
glycerol 3-phosphate dehydrogenase
Important enzymes of gluconeogenesis
pyruvate carboxylase
PEPCK
fructose-1,6-bisphophatase
glucose-6-phosphatase
pyruvate carboxylase
mitochondrial enzyme activated by acetyl CoA and produces OAA
PEPCK
induced by glucagon and cortisol
acts to raise blood sugar levels
converts OAA to PEP in a reaction that requires GTP
Fructose 1,6 bisphosphatase
key control point of gluconeogenesis and represents rate limiting step of the process
reverse the action of PFK-1, the RLS of glycolysis, by hydrolyzing phosphate from fructose 1,6-bisphosphate to produce fructose 6-phosphate
activated by ATP
inhibted by AMP
Glucose-6-phosphatase
converts glucose-6-phosphate into glucose
Alanine is the major __, but almost all amino acids are also __
glucogenic amino acid
glucogenic
Gluconeogenesis requires expenditure of ATP that is provided by __.
Beta-oxidation of fatty acids
hepatic gluconeogenesis always dependent on Beta-oxidation of fatty acids in the liver
Extended periods of low blood sugar are usually accompanied by __
serving as a source of ribose 5-phosphate for nucleotide synthesis
Parts of the PPP pathway
begins with glucose 6-phosphate, ends with ribulose 5-phosphate, and is irreversible
produces NADPH and involves the important rate limiting enzyme glucose-6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase (G6PD)
G6PD is induced by insulin because the abundance of sugar entering the cell under insulin stimulation will be shunted into both fuel utilization pathways (glycolysis and aerobic respiration) as well as fuel storage pathways
The shunt is also inhibted by its product, NADPH, and is activated by one of its reactants, NADP+
Second part of the pathway
represents series of reversible reactions that produce an equilibrated pool of sugars for biosynthesis, inclduign ribose 5-phosphate for nucleotide synthesis
NADPH acts as an __
electron donor in a number of biochemical reactions; ptent reducing agent
Cells require NADPH for:
biosnthesis
assisting in celular bleach production in certain white blood cells
maintenance of a supply of reduced glutathione to protect against reactive oxygen species