concept 1d part1 Flashcards
glucose entry into a cell
into most cells it is driven by concentration
is independent of sodium, unlike absorption from digestive tract
normal concentration in peripheral blood is 5.5 mM (range 4-6)
glucose transporters
GLUT 1 GLUT 2 GLUT 3 GLUT 4 2 and 4 are the most significant bc they are located in specific cells and are highly regulated
GLUT 2
low-affinity transporter
in hepatocytes (liver) and pancreatic cells
captures excess glucose from blood after a meal
primarily for storage
when glucose concentration drops below Km for the transporter (~15mM) most glucose leaves the liver and enters circulation
GLUT 4
in adipose tissue and muscle
responds to the glucose concentration in peripheral blood
stored in cytoplasm and when increased insulin triggers exocytosis and transporters move to the membrane
Km is ~5mM so transporter is saturated when blood glucose is a bit higher than normal
type 1 diabetes
insulin is absent and cannot stimulate the insulin receptors
blood glucose rises, leading to immediate and long-term symptoms
type 2 diabetes
receptors become insensitive to insulin and fail to bring GLUT 4 transporters to the cell surface
blood glucose rises, leading to immediate and long-term symptoms
diabetes symptoms
immediate- increased urination, increased thirst, ketoacidosis
long term- blindness, heart attacks, strokes, nerve damage
glycolysis
cytoplasmic pathway that converts glucose into 2 pyruvate
releasing energy captured in 2 substrate-level phosphorylations and 1 oxidation reaction
occurs under both aerobic and anaerobic conditions
energy carrier is NADH
5 enzymes of glycolysis
hexokinase and glucokinase phophofructokinases (PFK-1 and PFK-2) glyceraldehyde-3-phosphate dehydrogenase 3-phosphoglycerate kinase pyruvate kinase
hexokinase
converts glucose to glucose-6-phosphate in the first step of glycolysis, molecule is then trapped inside the cell
present in most tissues
low Km, reaches maximum velocity of low glucose concentration
inhibited by glucose 6-phosphate
glucokinase
converts glucose to glucose-6-phosphate in the first step of glycolysis, molecule is then trapped inside the cell
found only in the liver and pancreatic beta-islet cells
high Km, acts on glucose proportionally to its concentration
in the liver it is induced by insulin
phosphofructokinases-1 (PFK-1)
rate-limiting enzyme and main control point in glycolysis
fructose 6-phosphate is phosphorylated to fructose 1,6-biphosphate using ATP
inhibited by ATP and citrate
activated by AMP
in hepatocytes insulin stimulates and glucagon inhibits by indirect mechanism w/ PFK-2
phosphofructokinases-2 (PFK-2)
converts a tiny amount of fructose 6-P to fructose 2,6-biphosphate (F2,6-BP)
F2,6-BP activates PFK-1
activated by insulin and inhibited by glucagon
found mostly in the liver
glyceraldehyde-3-phosphate dehydrogenase
catalyzes an oxidation and addition of inorganic phosphate (Pi) to glyceraldehyde 3-P
results in high-energy intermediate 1,3-biphosphateglycerate
also reduction of NAD+ to NADH
3-phosphoglycerate kinase
transfers high-energy phosphate from 1,3-biphosphoglycerate to ADP
forms ATP and 3-phosphoglycerate, an example of substrate-level phosphorylation
substrate-level phosphorylation
ADP is directly phosphorylated to ATP using a high-energy intermediate
not dependent on oxygen, unlike oxidative phosphorylation
only means of ATP generation in anaerobic tissues
pyruvate kinase
catalyzes a substrate-level phosphorylation of ADP using high-energy substrate phosphoenolpyruvate (PEP)
activated by fructose 1,6-biphosphate from PFK-1 reaction
this is a feed-forward activation
feed-forward activation
meaning that the product of an earlier reaction stimulates, or prepares, a later reaction
fermentation
conversion of pyruvate to either ethanol and carbon dioxide (yeast) or lactic acid (animal cells)
happens in the absence of oxygen
result is replenishing NAD+
animal fermentation
pyruvate to lactic acid
key enzyme is lactate dehydrogenase
oxidizes NADH to NAD+, replenishing the oxidized coenzyme for glyceraldehyde-3-phosphate dehydrogenase
yeast cell fermentation
pyruvate (3C) to ethanol (2C) and carbon dioxide (1C)
results in replenishing of NAD+
intermediates of glycolysis
dihydroxyacetone phosphate (DHAP)
1,3-biphosphoglycerate (1,3-BPG)
phosphoenolpyruvate (PEP)
dihydroxyacetone phosphate (DHAP)
used in hepatic and adipose tissues
triacylglycerol synthesis
formed from fructose 1,6-bisphosphate
isomerized to glycerol-3-phosphate, then converted to glycerol which is the backbone of triacylglycerols
1,3-bisphosphate
high-energy intermediate
used to generate ATP by substrate-level phosphorylation, only ATP gained in anaerobic respiration
phosphoenolpyruvate
high-energy intermediate
used to generate ATP by substrate-level phosphorylation, only ATP gained in anaerobic respiration
irreversible enzymes
Hexokinase
Glucokinase
PFK-1
Pyruvate Kinase
How Glycolysis Pushes Forward the Process: Kinase (mnemonic)
glycolysis in erythrocytes
anaerobic glycolysis
only pathway for ATP production, 2 ATP per glucose
bisphosphoglycerate mutase produces 2,3-bisphosphogylcerate (2,3-BPG) from 1,3-BPG in glycolysis
2,3-BPG binds allosterically to beta-chain of hemoglobin A and decreases its affinity for oxygen in tissues
other monosaccahrides used by cells
galactose and fructose can contribute to ATP production by feeding into glycolysis or other metabolic processes
galactose
monosaccharide found in dairy, from disaccharide lactose
lactose
disaccharide found in milk
hydrolyzed to galactose and glucose by lactase in the duodenum
galactose metabolism
transported to the liver though the hepatic portal vein and transported to other tissues
then phosphorylated by galactokinase, trapping it in the cell, resulting in galactose 1-phosphate
that is then converted to glucose 1-phosphate by galactose-1-phosphate uridyltransferase and epimerase, which eventually results in glucose
*important enzymes: galactokinase and galactose-1-phosphate uridyltransferase
epimerase
enzymes that catalyze the conversion of one sugar epimer to another
primary lactose intolerance
caused by hereditary deficiency of lactase
lactose cannot be broken down
secondary lactose intolerance
precipitated at any age by gastrointestinal disturbances that cause damage to the intestinal lining where lactase is found
fructose
monosaccharide found in fruit and honey
sucrose is hydrolyzed by sucrase to form fructose and glucose
fructose metabolism
fructose is absorbed into the hepatic portal vein
liver phosphorylates fructose using fructokinase, trapping it in cell
results in fructose 1-phosphate, which is then cleaved into glyceraldehyde and DHAP by aldolase B
then forms glyceraldehyde 3-P used in glycolysis, glycogenesis, and gluconeogenesis
pyruvate dehydrogenase complex (PDH)
irreversible reaction
converts pyruvate to acetyl CoA for citric acid cycle
in the mitochondria
pyruvate dehydrogenase
in the liver activated by insulin
in the nervous system it is not responsive to hormones
converts pyruvate to acetyl CoA in the mitochondria
large complex of enzymes carrying out multiple reactions in succession, requires cofactors and coenzymes
inhibited by acetyl-CoA
glycogen
branced polymer of glucose
storage form of glucose
synthesis and degradation in the liver and skeletal muscle
stored in the cytoplasm as granules
glycogen granules
have central protein core with polyglucose chains radiating outward to form a sphere
composed entirely of linear chains w/ high density glucose near the core
liver glycogen
is broken down to maintain a constant level of glucose in the blood
muscle glycogen
is broken down to provide glucose to the muscle during vigorous exercise
glycogenesis
synthesis of glycogen granules
begins with core protein glycogenin
glucose addition to a granule begins with glucose 6-phosphate, converted to glucose 1-phosphate
activate by uridine diphosphate
permits integration into glycogen chain by glycogen synthase
glycogen synthase
rate-limiting enzyme of glycogen synthesis
forms alpha-1,4 glycosidic bonds found in linear glucose chains of granule
stimulated by glucose 6-phosphate and insulin
inhibited by epinephrine and glucagon
branching enzymes
responsible for introducing alpha-1,6-linked branches into granule
hydrolyzes one of the alpha-1,4 bonds to release block of oligoglucose, which is then moved and added to different location
this forms an alpha-1,6 bond to create branch
glycogenolysis
process of breaking down glycogen
rate-limiting enzyme is glycogen phosphorylate
glucose 1-phosphate formed by glycogen phosphorylate is converted to glucose 6-phosphate using same mutate as glycogen synthesis
glycogen phosphorylase
breaks alpha-1,4 bonds
releasing glucose 1-phosphate from periphery of granule
can’t break branches
activated by glucagon in liver and AMP and epinephrine in skeletal muscles
debranching enzymes
2 enzyme complex that deconstructs the branches in glycogen that have been exposed by glycogen phosphorylase
breaks alpha-1,4 bond adjacent to branch point and moves small oligoglucose chain that is release to exposed end of chain
forms a new alpha-1,4 bond
hydrolyzes the alpha-1,6 bond releasing the single residue at branch point as free glucose
gluconeogenesis
production of glucose from other biomolecules
carried out by liver and kidneys
helps maintain glucose levels during fasting
promoted by glucagon and epinephrine
inhibited by insulin
important substrates for gluconeogenesis
glycerol 3-phosphate: from stored fats, or triacylglycerols, in adipose tissue
lactate: from anaerobic glycolysis
glucogenic amino acids: from muscle proteins