Exam 2 Flashcards
1
Q
Primary functions of carbohydrates
A
- dietary source of calories
- energy storage (starch/glycogen)
- inter cell signaling pathways
- structure - bacterial cell walls; exoskeleton
2
Q
Classification
A
- number of carbons
2. most oxidized carbon (aldose or ketose)
3
Q
Maltose
A
Glucose + Glucose (alpha 1-4)
4
Q
Sucrose
A
Fructose + Glucose
5
Q
Lactose
A
Galactose + Glucose (beta 1-4)
6
Q
Polysaccharide
A
more than 12 monosaccharides
- glycogen (branched polysaccharide)
- homopolysaccharide or heteropolysaccharide
7
Q
Isomer
A
Same chemical formula
8
Q
Epimer
A
Same chemical formula and differ around only one of the carbons
9
Q
Enantiomer
A
Mirror Images of one another (D and L forms)
10
Q
Stereoisomer
A
Not mirror images (alpha and beta forms)
11
Q
Mutarotation
A
interconverting between alpha and beta forms
12
Q
Oligosaccharide
A
3-12 monosaccharides
13
Q
Equilibrium of D glucose
A
36% alpha - less than 1% linear - 64% beta
14
Q
Cyclization of Sugars
A
alcohol attacks carbonyl carbon. Draw Mechanism
15
Q
Most common enantiomer of glucose
A
D
16
Q
Carbohydrates attached to non-sugar molecules
A
glycosides
N-glycosidic linkage
O-glycosidic linkage
17
Q
Enzymes that catalyze the hydrolysis of glycosidic bonds
A
Glycosidases
- membrane-spanning enzymes found in the brush border of enterocytes (apical, luminal surface)
18
Q
Maltase
A
alpha 1-4 of maltose and maltotriose
19
Q
Isomaltase
A
alpha 1-6 of isomaltose
20
Q
Sucrase
A
alpha 1-2 of sucrose
21
Q
Lactase
A
beta 1-4 of lactose
22
Q
Trehalase
A
alpha 1-1 in trehalose (fungi)
23
Q
First step in digestion
A
alpha-amylase in mouth hydrolyzes random glycosidic bonds
Beta and disaccharides typically survive this step
24
Q
Primary digestive enzymes
A
Endoglycosidases Glycosidases (amylase) Disaccharidases
25
Endoglycosidases
release oligosaccharides
26
Why can't humans digest cellulose
Do not have beta 1-4 endoglycosidases
27
Digestion after mouth
alpha amylase is halted by the low acidity in the stomach
28
Digestion after stomach
bicarbonate from pancreas neutralizes upper intestinal tract and pancreatic alpha amylase is able to continue with digestion
29
Final site of digestion
mucosal lining of upper jejunum (brush border)
| - mucosal cell membrane-bound enzymes
30
Where does most of the absorption of dietary carbohydrates occur?
upper intestine (duodenum) and jejunum
31
What transports galactose and glucose into mucosal cells
SGLT1
| - cotransport with sodium, which participates in sodium potassium pump
32
Transport of fructose into mucosal cells
GLUT-5
33
Lactose intolerance
lactase deficiency
- bacteria in gut ferment unhydrolyzed lactose
- H2 oral tolerance test
- 2 and 3 carbon metabolites
34
Intolerance to sucrose
isomaltase-sucrase deficiency
35
Enzyme that transports glucose, galactose, and fructose to circulation
GLUT-2
36
racemases
interconverts between D and L enantiomers
37
end product of aerobic respiration
pyruvate
38
where does aerobic respiration typically occur
mitochondria
39
end product of anaerobic respiration
lactate
| - commonly seen in RBCs
40
what is GLUT-4 and where is it typically found
glucose transporter, found in adipose tissue and muscle
| - major insulin-responsive transporter
41
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
42
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)
43
what is the purpose of glycolysis
produce ATP
44
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)
45
what is GLUT-1 and where is it typically found
glucose transporter, found in most tissues
46
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
47
SGLT-1
Na+/glucose co-transporter
- present on apical side of intestinal brush border membrane cells.
- SPECIFIC FOR GLUCOSE
48
what are the two phases of aerobic glycolysis?
1. energy investment
| 2. energy generation
49
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)
50
how many ATP are used during the energy investment phase of glycolysis?
2
51
how many ATP are generated during the energy generation phase of glycolysis?
4
52
how many NADH are generated during the energy generation phase of glycolysis?
2
53
What is the primary enzyme that phosphorylates fructose
fructokinase
| typically hexokinase is too saturated with glucose to deal with fructose
54
is fructose insulin-dependent or insulin independent
insulin independent
55
where is fructose found as a free monosaccharide
fruits, honey, HFCS
56
what is the important role of galactose
cell structural
57
does fructose initiate insulin secretion
no
58
where is fructokinase primarily found?
liver (where majority of dietary fructose is processed), kidney, small intestine
59
how does fructose enter the cell
GLUT-5
60
what compound does fructose become when phosphorylated by fructokinase?
fructose 1-phoshpate
61
what compound does fructose become when phosphorylated by hexokinase?
(rarely happens)
| fructose 6-phosphate
62
which basic group of enzymes is responsible for breaking the hexose form of the monosaccharides into the triode form?
aldolase
63
which aldolase catalyzes the reaction from fructose 1-phosphate to glyceraldehyde?
aldolase B
64
how is glyceraldehyde (from fructose 1-phosphate) converted to glyceraldehyde 3-phosphate to continue in the glycolytic pathway?
glyceraldehyde kinase
65
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
66
which enzyme converts glucose 6-phosphate to glucose 1,6-bisphosphate?
phosphofructokinase
67
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
68
Mannose
- key component of glycoproteins
- very little is consumed in the typical diet
1. converted to mannose 6-phosphate by hexokinase
2. converted to fructose 6-phosphate by phosphomannose isomerase
3. continues along glycolysis pathway
69
pylol
sugar alcohol
70
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)
71
which enzyme produces sorbitol from glucose
aldose reductase
72
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
73
where is the enzyme aldose reductase found
lens and retina
peripheral nerves (Schwann cells)
kidney
placenta
74
where is the enzyme sorbitol dehydrogenase found?
liver
ovaries
seminal vescicles
75
which cells specifically prefer fructose as their carbohydrate substrate?
sperm cells
76
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.
77
How is galactose typically consumed in the diet, and how is it converted to its monosaccharide form
lactose
| beta-galactosidase enzyme cleaves
78
which enzyme phosphorylates galactose to commit it to metabolism?
galactokinase
- becomes galactose 1-phosphate
79
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
80
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
81
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
82
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)
83
what makes up high fructose corn syrup
55% fructose, 45% glucose
84
which mechanisms control the flow of intermediates through the metabolic pathways?
1. substrate availability
2. allosteric activation or inhibition
3. covalent modification of enzymes
4. induction/repression of enzyme synthesis
- also consider types of transporters
85
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
86
how is glucose an allosteric effector of metabolism?
1. elevated glucose stimulates the release of glucokinase from the glucokinase regulatory protein (in the nucleus), which allows it to more rapidly carry out metabolism.
2. glucose inhibit liver glycogen phosphorylase (so glycogen is not broken down - glycogenolysis)
87
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
88
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
89
enzymes that are induced at the transcriptional level by glucose
pyruvate kinase (liver)
acetyl CoA carboxylase (fatty acid synthesis regulatory enzyme)
fatty acid synthase
90
Pasteur effect
in the presence of oxygen, lactate production is reduced
91
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
92
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)
93
In normal cells, what does issues with ECM attachment cause?
increase is ROS production, which leads to anoikis (protective mechanism from metastasis)
94
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"
95
what do p53 and KISS1 do?
p53 is a tumor suppressor and KISS1 is a metastasis suppressor. Both promote mitochondrial oxidation
96
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
97
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
