Biochem #9 Flashcards
1
Q
glucose entry into the cells is driven by ____
A
concentration
2
Q
what are the names of the glucose transporters?
A
GLU 1-4
3
Q
GLUT 2
A
low-affinity transport in hepatocytes and pancreatic cells.
Captures glucose in the hepatic portal vein from the intestine
Km of GLUT 2 is high ~ 15mM
Liver will pick up extra glucose and store it preferentially after a meal.
Along with the glycolytic enzyme glucokinase, it is a glucose sensor for insulin release.
First order kinetics
4
Q
GLUT 4
A
in adipose tissue and muscle and responds to glucose concentration in peripheral blood.
Rate of glucose transport is increased by insulin
Km is ~5mM, so these are saturated at just over normal blood glucose levels.
Zero order kinetics, when a person has high glucose concentration, transports will only permit a constant rate of glucose.
• Can increase how much a cell takes in by increasing the # of transporters on the surface.
Basal levels of transport occur in all cells independently of insulin, transport rate increases in adipose tissue and muscle when insulin levels rise.
• Muscle: store as glycogen
• Adipose: glucose dihydroxyacetone phosphate (DHAP) glycerol for triacylglycerols.
5
Q
Does GLUT 2 or GLUT 4 have higher affinity for glucose?
A
GLUT 4, lower Km
6
Q
how is glucose stored differently in muscle vs. adipose tissue
A
muscle: glycogen
adipose: triglycerol
7
Q
what are the phases of fasting?
A
- glycogenolysis immediately
- gluconeogensis: intermediate to late fasting
- liver cells producing more glucose (little glucokinase activity)
8
Q
what is the average blood glucose in peripheral cells?
A
5.6 mM
9
Q
what cells carry out glycolysis?
A
All cells can carry out glycolysis, even red blood cells with their hemoglobin (it is actually their only way to get ATP).
10
Q
difference between glycogenolysis and glycogenesis
A
Glycogenolysis: breakdown of glycogen
Glycogenesis: creation of glycogen
11
Q
how much ATP is yielded from glycolysis alone from one molecule of glucose?
A
2 ATP (1 per pyruvate)
12
Q
kinase
A
attaches P
13
Q
phoshatase
A
removes P
14
Q
glycolysis
A
a cytoplasmic pathway that converts glucose into two pyruvate molecules, releasing a modest amount of energy capture in two substrate-level phosphorylation and one oxidation reaction.
15
Q
where does glycolysis take place?
A
cytosol
16
Q
what do hexokinase and glucokinase do?
A
glucose ==> glucose 6-phosphate
Attaching a P group makes the glucose not able to leave the cell once it has entered.
17
Q
where is hexokinase found?
A
widely distributed in tissues and is inhibited by glucose 6-phosphate as well.
18
Q
where is glucokinase found?
A
found only in liver and pancreatic Beta cells.
Induced by insulin.
19
Q
what is the rate limiting step of glycolysis?
A
phosphofructokinase I
20
Q
what can override the inhibition of ATP on PFK-1?
A
PFK 2 and the production of fructose 2,6-bisphosphate
21
Q
what are the fates of pyruvate?
A
gluconeogenesis, citric acid cycle, fermentation, fatty acid synthesis
22
Q
difference between yeast and humans fermentation
A
o When oxygenation is poor (like during strenuous exercise in skeletal muscle), most cellular ATP is generated by anaerobic glycolysis, and lactate production increases.
o In yeast cells, fermentation results in the conversion of pyruvate to ethanol and carbon dioxide while it also replenishes the NAD+.
23
Q
what are the irreversible steps of glycolysis?
A
- glucokinase/hexokinase
- PFK-1
- pyruvate kinase
24
Q
what decreases the affinity of hemoglobin for oxygen in erythrocytes?
A
2,3-BPG
25
how does galactose integrate into glycolysis?
produced from breaking down lactose (produces glucose and galactose)
o Source of galactose is lactose
Hydrolyzed to glucose and galactose by lactase in duodenum.
o Galactose reaches the liver via the hepatic portal vein.
o Transported to other tissues, phosphorylated by galactokinase which keeps it in the cell.
o Then, galactose 1-phosphate is converted to glucose 1-phosphate by galactose-1-phosphate uridyltransferase and epimerase.
26
how does fructose integrate into glycolysis?
produced from breaking down sucrose (produces glucose and fructose)
o Fructose is found in honey and fruit and as part of the disaccharide sucrose.
o Sucrose broken down by sucrase in the duodenum, monosaccharides are absorbed through the hepatic portal vein.
o Liver phosphorylates fructose via fructokinase and traps it in the cell.
o Aldolase B cleaves fructose 1-phosphate into glyceraldehyde and DHAP (downstream of rate limiting step in glycolysis which is why a very sugary drink provides quick source of energy)
27
glycogen
branched polymer of glucose
28
where does glycogen storage mainly occur?
liver and skeletal muscle
29
glycogenesis
: the synthesis of glycogen granules.
o Starts with glucose 6-phosphate glucose 1-phosphate UDP-glucose integrated into glycogen.
o Glycogen synthase: the rate limiting enzyme of glycogen synthesis and forms an alpha-1,4 glyosidic bond found in the linear glucose chains of the granule.
Stimulated by glucose 6-phosphate and insulin.
o Branching Enzyme (glycosyl alpha-1:alpha-1,6 transferase): responsible for introducing the alpha 1,6 linked branches into the granule as it grows.
Glycogen synthesis keeps adding forward while branching enzyme adds a branch.
30
glycogen synthase
the rate limiting enzyme of glycogen synthesis and forms an alpha-1,4 glyosidic bond found in the linear glucose chains of the granule.
Stimulated by glucose 6-phosphate and insulin.
31
linkages in regular glycogen synthesis vs. branch
regular: 1,4
branch: 1,6
32
glycogenolysis
process of breaking down glycogen
o Rate limiting enzyme is glycogen phosphorylase.
o Glycogen Phosphorylase: breaks alpha-1,4 glyosidic bonds, releasing a glucose 1-phosphate from the periphery of the granule.
cannot break alpha-1,6 bonds so it stops near branches.
33
debranching enzyme
: a two-enzyme complex (1 transfers the alpha 1,4 to new branch and one removes the glucose monomer present at the branch) that deconstructs the branches in glycogen that have been exposed to glycogen phosphorylase.
o Takes off and moves the branch to the extending chain
o One remaining glucose left that has an alpha-1,6 bond, this is broken and releases a free glucose.
34
what is the only time ever that a free glucose is released directly?
debranching enzyme last glucose on the chain connected with 1,6 linkage that has to be taken off.
35
____ are used in glycogen synthesis
glycosidic bonds
36
what is the main contributor of gluconeogenisis?
liver
37
what are the important substrates for gluconeogenisis?
o Glycerol 3-phosphate (from stored fats, triacylglycerols, in adipose tissue)
Converted to DHAP by glycerol-3-phoshpate dehydrogenase
o Lactate (from anaerobic glycolysis)
Converted to pyruvate via lactate dehydrogenase
o Glucogenic amino acids (from muscle proteins)
Alanine is converted to pyruvate by alanine aminotransferase
Glucogenic amino acids: all except leucine and glycine, can be converted into intermediates that feed into gluconeogenesis
Ketogenic amino acids: can be converted into ketone bodies which can be used as fuel during prolonged periods of starvation.
38
what are the important substrates for gluconeogenisis?
o Glycerol 3-phosphate (from stored fats, triacylglycerols, in adipose tissue)
Converted to DHAP by glycerol-3-phoshpate dehydrogenase
o Lactate (from anaerobic glycolysis)
Converted to pyruvate via lactate dehydrogenase
o Glucogenic amino acids (from muscle proteins)
Alanine is converted to pyruvate by alanine aminotransferase
Glucogenic amino acids: all except leucine and glycine, can be converted into intermediates that feed into gluconeogenesis
Ketogenic amino acids: can be converted into ketone bodies which can be used as fuel during prolonged periods of starvation.
39
glucogenic amino acids
all except leucine and lysine, can be converted into intermediates that feed into gluconeogenesis
40
ketogenic amino acids
can be converted into ketone bodies which can be used as fuel during prolonged periods of starvation. Leucine and lysine.
41
what are the important enzymes in gluconeogenesis
o 1. Pyruvate Carboxylase: mitochondrial enzyme that is activated by acetyl-CoA (from Beta-oxidation)
Oxaloacetate is the product.
Acetyl-CoA comes from fatty acid breakdown in this case
Acetyl-CoA activates pyruvate carboxylase and inhibits pyruvate dehydrogenase.
o 2. Phosphoenolpyruvate Carboxykinase (PEPCK): in the cytoplasm, induced by glucagon and cortisol.
Converts OAA to PEP in a reaction that involves GTP
o 3. Fructose-1,6-Bisphosphatase: in the cytoplasm, rate limiting step of gluconeogenesis.
Reverses the action of PFK-1
Inhibited by F2,6-BP
Converts fructose 1,6-bis P to fructose 6-P
o 4. Glucose-6-Phosphatase: found only in the lumen of the ER in liver cells.
There is none in skeletal muscle which means that muscle glycogen cannot serve as a source of blood glucose and rather is for use only within the muscle.
42
Hepatic gluconeogenesis is always dependent on ______ in the liver and glucose produced by hepatic gluconeogenesis ____
Beta-oxidation of fatty acids
| does not represent an energy source for the liver.
43
Acetyl-CoA can be converted into _____ as an alternate fuel source.
ketone bodies
Extended periods of low blood sugar are accompanied by high levels of ketone in the blood.
44
cori cycle
glucose is converted to lactate in red blood cells (to regenerate NAD+ for anaerobic glycolysis), and lactate is converted to glucose in liver cells (to remove the acidic lactate from the blood).
45
where does the pentose phosphate pathway occur?
occurs in the cytoplasm of all cells
46
what does the pentose phosphate pathway produce?
o 1. Production of NADPH
o 2. Souce of ribose 5-phosphate for nucleotide synthesis.
• There is also easy interconversion between the sugars and certain intermediates in the glycolysis pathway.
47
what are the functions of NADPH
o Acts as an electron donor
o 1. Biosynthesis of fatty acids and cholesterol
o 2. Bactericidal activity
o 3. Protect against reactive oxygen species by maintaining supply of glutathione (reducing agent that can help reverse radical formation before damage is done to the cell).
Protect from free radical oxidative damage caused by peroxides.
48
what is the normal glucose concentration in blood
5.6 mM (between 4-6)
49
what are the sensors for insulin release in beta islet cells of the pancreas?
GLUT 2 glucose receptor and glucokinase
50
compare the location of GLUT 2 and GLUT 4
GLUT 2: hepatocytes and pancreatic cells
| GLUT 4: adipose tissue and muscle cells
51
compare the Km of GLUT 2 and GLUT 4
GLUT 2: 15 mM
| GLUT 4: 5 mM
52
compare diabetes type I and type II
type I: insulin is absent and cannot stimulate the insulin receptor
type II: insulin receptor is insensitive to insulin and does not bring GLUT 4 receptor to surface
53
Is GLUT 2 responsive to insulin?
no, but in addition to glucokinase, it acts as a glucose sensor which causes insulin release.
54
what is the only way red blood cells get energy?
glycolysis
55
where does glycolysis occur?
cytoplasm
56
how does not having mitochondria help red blood cells?
gives them more volume to host more hemoglobin (oxygen carrier)
does not use up the oxygen that it is supposed to be transporting.
57
are there any diseases that completely knockout an enzyme in glycolysis?
no, because it is so important in every cell of the body, lack of being able to carry out glycolysis is incompatible with life.
58
what does phosphorylating glucose into glucose-6 phosphate do once it enters the cell?
prevents it from leaving back thru the transporter.
59
what increases glucokinase activity?
insulin
60
what decreases hexokinase activity?
glucose-6 phosphate product (negative feedback)
61
what inhibits PFK-1?
ATP and citrate
62
what activates PFK-1?
AMP and fructose-2,6-bisphosphate (in hepatocytes)
63
what process overrides high ATP levels in liver cells to continue glycolysis?
fructose 2,6 bisphosphate production by PFK-2
64
where does PFK-2 function?
liver, continues glycolysis so its metabolites can be used for the production of glycogen, fatty acids, and other storage molecules rather than just being burned to produce ATP.
65
substrate-level phosphorylation
ADP is directly phosphorylated to ATP using a high energy intermediate
66
what activates pyruvate kinase?
F16BP
67
how does the body adapt to high altitude?
- increased respiration
- increase oxygen affinity for hemoglobin initially
- increase rate of glycolysis
- increased 2,3 BPG in RBC over 12-24 hours
- normalized oxygen affinity for hemoglobin restored by increased 2,3 BPG
- increased hemoglobin (over few days to weeks)
68
2,3 BPG binds allosterically to hemoglobin and ____ affinity for oxygen
decreases
69
does 2,3 BPG bind to HbF?
No, allows transplacental passage of oxygen
70
how does glucagon regulate PFK-1 activity?
decreases it as glucagon indicates that glucose needs to be released into the blood, not broken down.
71
what is the main role of fermentation?
it regenerates the coenzymes needed in glycolysis.
72
coenzymes vs, cofactors
Coenzymes are organic molecules and quite often bind loosely to the active site of an enzyme and aid in substrate recruitment, whereas cofactors do not bind the enzyme.
73
epimerase
catalyzes the conversion of one sugar epimer to another
74
compare primary and secondary lactose intolerance
primary: hereditary deficiency of lactase
secondary: occurs at any age due to gastrointestinal disturbances that cause damage to the intestinal lining where lactase is found
75
what type of enzyme is lactase?
brush border enzyme of the duodenum
76
what type of enzyme is sucrase?
brush border enzyme of the duodenum
77
is hexokinase related to fructose at all?
yes, it can convert fructose to fructose 1 phosphate (just slower than fructokinase can)
78
what activates pyruvate dehydrogenase in the liver? What inhibits it?
insulin
| acetyl-CoA
79
what is unique about pyruvate dehydrogenase
it is a complex of enzymes that act in succession.
80
what syndrome is thymine deficiency a cause of?
Wernicke-Korsakoff syndrome
81
in a straight glycogen molecule where is the most dense region of glucose? Branched? Which allows more rapid release of glucose?
core
periphery
branched/periphery
82
what is the difference between glycogen storage in the liver and skeletal muscle?
glycogen is used to in the liver to break down and supply glucose to the blood when needed.
glycogen in skeletal muscle is broken down and used during intense exercise.
83
starch
long, alpha linked chains fo glucose
84
what is the name of the core protein that is used for glycogenisis?
glycogenin
85
what is the name of the glycosidic bond in linear glucose?
alpha 1-4 glycosidic bond
86
describe steps of the glycogen branching enzyme
cuts a 1,4 linkage, transfers the oligoglucose unit and attaches it with an alpha 1,6 linkage to create a branch, glycogen synthase extends both ends now.
87
how does a phosphorylase differ from a hydrolase?
phosphorylase breaks bonds using an inorganic phosphate instead of water
88
what activates glycogen phosphorylase in the liver and in the skeletal muscle?
glucagon in the liver
| AMP and epinephrine in skeletal muscle
89
what is the only time during glycogenesis that a free glucose is released?
the last glucose attached to the alpha 1,6 glycosidic linkage via branching
90
isoform
slightly different versions of the same protein (such glycogen storage enzymes in the liver vs. the muscle)
91
what two organs carry out gluconeogenesis
liver and kidney (smaller amount)
92
can fatty acids be broken down to glucose?
yes, odd number C fatty acids can
93
what enzyme converts alanine to pyruvate
alanine aminotransferase
94
where is glucose-6 phosphate found?
only in the lumen of the ER of liver cells.
95
hepatic gluconeogenesis is always dependent on _______ in the liver and the glucose that is produced _____
beta oxidation of fatty acids in the liver
| is not for energy use by the liver.
96
gluconeogenesis requires ____ to occur
acetyl CoA from beta oxidation
97
under what physiological conditions should the body carry out gluconeogenesis?
low blood glucose, fasting for >12 hours.
98
what activates and inhibits the pentose phosphate pathway?
activates: insulin, NADP+
inhibits: NADPH (which is a product)
99
NADH vs. NADPH
NADH: NAD+ is high energy electron acceptor: electron transport chain, energy carrier
NADPH: NADPH is electron donor: biosynthesis of fatty acids and cholesterol, cellular bleach production (immune system), protect against reactive oxygen species (maintenance of supply of glutathione)
100
what can ribose-5-phosphate be used for?
can be coupled to a nitrogenous base to form a nucleotide.
101
glutathione
supply is maintained by NADPH, it is a reducing agent that can help reverse radical formation before damage is done to the cell.
102
where does gluconeogenesis occur?
both the cytoplasm and the mitochondria
103
what do red blood cells, the brain, and the pancreas have in common with regards glucose during a fast?
they need a constant supply from the blood
| whereas the liver and somewhat the kidney can produce it through gluconeogenesis
104
citrate inhibits which part of glycolysis
PFK-1 activity
105
if a cell is energetically satisfied, will there be more NADH or NAD+?
NADH
106
in fasting, does glycogenolysis or gluconeogenesis occur first
glycogenolysis
