Exam 2 Flashcards
Primary functions of carbohydrates
- dietary source of calories
- energy storage (starch/glycogen)
- inter cell signaling pathways
- structure - bacterial cell walls; exoskeleton
Classification
- number of carbons
2. most oxidized carbon (aldose or ketose)
Maltose
Glucose + Glucose (alpha 1-4)
Sucrose
Fructose + Glucose
Lactose
Galactose + Glucose (beta 1-4)
Polysaccharide
more than 12 monosaccharides
- glycogen (branched polysaccharide)
- homopolysaccharide or heteropolysaccharide
Isomer
Same chemical formula
Epimer
Same chemical formula and differ around only one of the carbons
Enantiomer
Mirror Images of one another (D and L forms)
Stereoisomer
Not mirror images (alpha and beta forms)
Mutarotation
interconverting between alpha and beta forms
Oligosaccharide
3-12 monosaccharides
Equilibrium of D glucose
36% alpha - less than 1% linear - 64% beta
Cyclization of Sugars
alcohol attacks carbonyl carbon. Draw Mechanism
Most common enantiomer of glucose
D
Carbohydrates attached to non-sugar molecules
glycosides
N-glycosidic linkage
O-glycosidic linkage
Enzymes that catalyze the hydrolysis of glycosidic bonds
Glycosidases
- membrane-spanning enzymes found in the brush border of enterocytes (apical, luminal surface)
Maltase
alpha 1-4 of maltose and maltotriose
Isomaltase
alpha 1-6 of isomaltose
Sucrase
alpha 1-2 of sucrose
Lactase
beta 1-4 of lactose
Trehalase
alpha 1-1 in trehalose (fungi)
First step in digestion
alpha-amylase in mouth hydrolyzes random glycosidic bonds
Beta and disaccharides typically survive this step
Primary digestive enzymes
Endoglycosidases Glycosidases (amylase) Disaccharidases
Endoglycosidases
release oligosaccharides
Why can’t humans digest cellulose
Do not have beta 1-4 endoglycosidases
Digestion after mouth
alpha amylase is halted by the low acidity in the stomach
Digestion after stomach
bicarbonate from pancreas neutralizes upper intestinal tract and pancreatic alpha amylase is able to continue with digestion
Final site of digestion
mucosal lining of upper jejunum (brush border)
- mucosal cell membrane-bound enzymes
Where does most of the absorption of dietary carbohydrates occur?
upper intestine (duodenum) and jejunum
What transports galactose and glucose into mucosal cells
SGLT1
- cotransport with sodium, which participates in sodium potassium pump
Transport of fructose into mucosal cells
GLUT-5
Lactose intolerance
lactase deficiency
- bacteria in gut ferment unhydrolyzed lactose
- H2 oral tolerance test
- 2 and 3 carbon metabolites
Intolerance to sucrose
isomaltase-sucrase deficiency
Enzyme that transports glucose, galactose, and fructose to circulation
GLUT-2
racemases
interconverts between D and L enantiomers
end product of aerobic respiration
pyruvate
where does aerobic respiration typically occur
mitochondria
end product of anaerobic respiration
lactate
- commonly seen in RBCs
what is GLUT-4 and where is it typically found
glucose transporter, found in adipose tissue and muscle
- major insulin-responsive transporter
what is GLUT-2 and where is it typically found
glucose transporter, found in liver, pancreatic beta cells, basolateral side of brush border membrane of intestine, and kidneys
what is GLUT-3 and where is it typically found
glucose transporter, found in neurons, with lower levels in other tissues (NOT IN SKELETAL MUSCLE)
what is the purpose of glycolysis
produce ATP
two types of transport
facilitated - moves down a concentration gradient
co-transport - moves with Na+ against the concentration gradient (requires energy) (epithelial cells of intestine and renal tubules)
what is GLUT-1 and where is it typically found
glucose transporter, found in most tissues
what is GLUT-5 and where is it typically found
glucose transporter, apical side of intestinal brush border membrane cells, sperm, and fructose-metabolizing tissues
- SPECIFIC FOR FRUCTOSE
SGLT-1
Na+/glucose co-transporter
- present on apical side of intestinal brush border membrane cells.
- SPECIFIC FOR GLUCOSE
what are the two phases of aerobic glycolysis?
- energy investment
2. energy generation
definition of glycolysis
the formation of 2 molecules of pyruvate or lactate from one molecule of glucose with the net production of 2 ATPs (and 2 NADH)
how many ATP are used during the energy investment phase of glycolysis?
2
how many ATP are generated during the energy generation phase of glycolysis?
4
how many NADH are generated during the energy generation phase of glycolysis?
2
What is the primary enzyme that phosphorylates fructose
fructokinase
typically hexokinase is too saturated with glucose to deal with fructose
is fructose insulin-dependent or insulin independent
insulin independent
where is fructose found as a free monosaccharide
fruits, honey, HFCS
what is the important role of galactose
cell structural
does fructose initiate insulin secretion
no
where is fructokinase primarily found?
liver (where majority of dietary fructose is processed), kidney, small intestine
how does fructose enter the cell
GLUT-5
what compound does fructose become when phosphorylated by fructokinase?
fructose 1-phoshpate
what compound does fructose become when phosphorylated by hexokinase?
(rarely happens)
fructose 6-phosphate
which basic group of enzymes is responsible for breaking the hexose form of the monosaccharides into the triode form?
aldolase
which aldolase catalyzes the reaction from fructose 1-phosphate to glyceraldehyde?
aldolase B
how is glyceraldehyde (from fructose 1-phosphate) converted to glyceraldehyde 3-phosphate to continue in the glycolytic pathway?
glyceraldehyde kinase
what is the primary rate-limiting step in glycolysis that is avoided by fructose metabolism (beginning with fructokinase)?
conversion of glucose 6-phosphate (or fructose 6-phosphate) to glucose 1,6-bisphosphate
which enzyme converts glucose 6-phosphate to glucose 1,6-bisphosphate?
phosphofructokinase
what is hereditary fructose intolerance?
caused by a deficiency or mutation in aldolase B enzyme. This results in a buildup of fructose 1-phosphate, which inhibits Aldolase A (much bigger deal)
the inhibition of aldolase A results in a decrease in ATP production by inhibiting glycolysis and gluconeogenesis
Mannose
- key component of glycoproteins
- very little is consumed in the typical diet
- converted to mannose 6-phosphate by hexokinase
- converted to fructose 6-phosphate by phosphomannose isomerase
- continues along glycolysis pathway
pylol
sugar alcohol
what is the significance of pylon in carbohydrate metabolism
it is an alternate method for metabolizing sugars. (converting them to a sugar alcohol by reducing the aldehyde group)
which enzyme produces sorbitol from glucose
aldose reductase
what happens after glucose is converted to sorbitol by aldose reductase?
it is oxidized by sorbitol dehydrogenase to fructose
- this is done in specific tissues only
where is the enzyme aldose reductase found
lens and retina
peripheral nerves (Schwann cells)
kidney
placenta
where is the enzyme sorbitol dehydrogenase found?
liver
ovaries
seminal vescicles
which cells specifically prefer fructose as their carbohydrate substrate?
sperm cells
How is sorbitol significant in hyperglycemia?
extremely high blood glucose levels lead to increased sorbitol production (if enough NADPH is present) because glucose can enter the specific tissue types described here in an insulin-independent manner. The sorbitol builds up in the lens and nerve cells because sorbitol is not very membrane-permeable. Osmotic effect causes water to flow into the cells, causing swelling.
- associated with inflammation, cataract formation, peripheral neuropathy, microvascular damage.
How is galactose typically consumed in the diet, and how is it converted to its monosaccharide form
lactose
beta-galactosidase enzyme cleaves
which enzyme phosphorylates galactose to commit it to metabolism?
galactokinase
- becomes galactose 1-phosphate
what must happen to galactose before it can enter the glycolytic pathway?
it must be converted to UDP-galactose via the transfer of UDP groups between UDP-glucose and galactose
- catalyzed by GALT
galactose 1-phosphate uridyltransferase
how is lactose synthesized?
consists of beta-galactose and glucose
- synthesized in the golgi by lactose synthase, which transfers galactose from UDP-galactose and releases free UDP
lactose synthase (very general structure)
beta-D-galactosyltransferase (found in many tissues) dimerizes with alpha-lactalbumin (found only in lactating mammary gland - stimulated by prolactin) to form lactose synthase
what else does beta-D-galactosyltransferase do?
in tissues other than mammary glands, it functions in the biosynthesis of N-acetyllactosamine (component of N-linked glycoproteins)
what makes up high fructose corn syrup
55% fructose, 45% glucose
which mechanisms control the flow of intermediates through the metabolic pathways?
- substrate availability
- allosteric activation or inhibition
- covalent modification of enzymes
- induction/repression of enzyme synthesis
- also consider types of transporters
what is the effect of the kinetics of glucokinase vs hexokinase?
glucokinase has a lower affinity and a higher vmax, which means that it can more rapidly produce glucose 6-phosphate (primarily seen in the liver)
- I’m still not 100% sure what structural features lead to the increased vmax
how is glucose an allosteric effector of metabolism?
- elevated glucose stimulates the release of glucokinase from the glucokinase regulatory protein (in the nucleus), which allows it to more rapidly carry out metabolism.
- glucose inhibit liver glycogen phosphorylase (so glycogen is not broken down - glycogenolysis)
how does glucose stimulate transcription of relevant genes?
through glucose-responsive regions of gene promoters (such as ChoREs)
- example is the elevated expression of pyruvate kinase in the liver with elevated glucose levels
ChoRE
carbohydrate response element
- 2 E-box elements separated by 5 nucleotides
- recognized by transcription factors ChREBP (carbohydrate response element binding protein), which dimerizes with Mlx and binds to the E-box
- notably, the effect is not due to glucose itself, but is instead due to compounds generated during glucose metabolism
enzymes that are induced at the transcriptional level by glucose
pyruvate kinase (liver)
acetyl CoA carboxylase (fatty acid synthesis regulatory enzyme)
fatty acid synthase
Pasteur effect
in the presence of oxygen, lactate production is reduced
Some characteristics of cancer cells
- 10-fold increase in glucose consumption
- 2 orders of magnitude more lactate production
- Warburg effect - cancer cells produce lactate even in the presence of oxygen
NOX
NADPH oxidase
- activated by the activation of Ras and by the loss of p53 - typically seen in defective mitochondria.
- increases aerobic glycolysis (characteristic of CA)
In normal cells, what does issues with ECM attachment cause?
increase is ROS production, which leads to anoikis (protective mechanism from metastasis)
what are two examples of pro-metastatic TFs in cancer cells and what do they encourage?
HIF and Snail, promote the diversion to lactate, avoiding oxidative phosphorylation
- “attenuate oxidative metabolism”
what do p53 and KISS1 do?
p53 is a tumor suppressor and KISS1 is a metastasis suppressor. Both promote mitochondrial oxidation
how does FDG enter cells, and what is it used for?
it is used in PET scans, and it enters through GLUT-1 and GLUT-3 channels.
- it is phosphorylated by hexokinase to FDG-6-phosphate, but cannot move further along in the process (because there is no oxygen at the C2).
- uptake depends on both transporter activity and hexokinase activity
which tissues are difficult to diagnose using PET scans?
tissues with poor perfusion, tissues with lots of background noise (prostate)
tumor types that do not exhibit the warburg effect
