EXAM 1 Flashcards

(187 cards)

1
Q

AT 37℃≈ …?

ΔG°’ ➙ [B]/[A]

A

37℃≈ -6log Keq

ΔG°’ [B]/[A]
0 1
-6 10
-12 100
6 0.1
12 0.01

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2
Q

name the energy compounds that are substantially higher energy than ATP vs roughly comparable

A

higher energy:

✩ Phosphoenolpyruvate (PEP)
✩ 1,3-Bisphosphoglycerate (1,3 BPG)

roughly comparable to ATP:

✫Phosphocreatine (P-creatine)
✫ Thioester bonds ( ex. in Acetyl-CoA)
✫ UDP-Gluc
✬ other NTP

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3
Q

List the most oxidized to most reduced form of carbon

A
  • Carboxylic Acid
  • Aldehyde ( or Ketone)
  • Alcohol (Alkene)
  • Alkane
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4
Q

Draw structure of ATP

A

Slide 24 of lecture 1

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5
Q

Draw structure of 1,3 BPG

A

slide 28 of lec 1

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6
Q

Draw PEP —> Pyruvate

A

slide 27 of lec 1

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7
Q

Acetyl CoA contains___, which is a ____

A

Pantothenic acid, vitamin

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8
Q

What vitamin is found in the nicotinamide part of NADH and what is the deficiency of it called?

A

Niacin; Pellegra

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9
Q

Draw the structure of NAD+ and NADH?

A

Slide 46 of lec. 1

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10
Q

What vitamin is FADH2 made out of?

A

Riboflavin

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11
Q

Which steps in glycolysis are irreversible and serve as regulatory points?

A

✪ hexokinase (step 1)
✪phosphofructokinase-1 (step 3)
✪pyruvate kinase (step 10).

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12
Q

T/F glycolysis occurs in the mitochondria

A

FALSE. It occurs in the cytoplasm of the cell.

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13
Q

What is the first step of glycolysis?

A

the phosphorylation of glucose to form glucose-6-phosphate, catalyzed by the enzyme hexokinase.

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14
Q

Which enzyme is responsible for converting glucose-6-phosphate into fructose-6-phosphate?

A

The enzyme phosphoglucose isomerase

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15
Q

What is the role of phosphofructokinase-1 (PFK-1) in glycolysis?

A

PFK-1 is a key regulatory enzyme in glycolysis that catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate

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16
Q

What are the end products of glycolysis?

A

2 molecules of pyruvate, 2 molecules of NADH, and a net gain of 2 ATP molecules.

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17
Q

How does glycolysis contribute to anaerobic respiration?

A

In anaerobic conditions, pyruvate produced from glycolysis can be converted into lactate (in animals) or ethanol (in yeast) to regenerate NAD+, allowing glycolysis to continue producing ATP.

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18
Q

What is the fate of pyruvate after glycolysis under aerobic conditions?

A

Under aerobic conditions, pyruvate is transported into the mitochondria and converted into acetyl-CoA, which enters the citric acid cycle (Krebs cycle) for further energy production.

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19
Q

What happens in the fourth step of glycolysis, and which enzyme is responsible?

also state which one is a ketose and which one is an aldehyde

A

fructose-1,6-bisphosphate is cleaved into two three-carbon molecules: glyceraldehyde-3-phosphate (GAP)
(aldehyde)
and dihydroxyacetone phosphate (DHAP). (ketose)

The enzyme responsible is aldolase (*and Triose phosphate Isomerase)

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20
Q

T/F aldolase alone converts fructose-1,6-bisphosphate to GAP + DHAP

A

FALSE; it needs Triose Phosphate Isomerase as well

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21
Q

Describe the fifth step of glycolysis and the enzyme involved.

A

conversion of dihydroxyacetone phosphate (DHAP) into glyceraldehyde-3-phosphate (GAP).

The enzyme involved is triose phosphate isomerase. (it has to catch up :0 )

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22
Q

T/F every reaction of glycolysis requires Oxygen

A

FALSE; none of the reactions require O2

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23
Q

T/F Taking large amounts of vitamin B1 can enhance athletic performance by stimulating pyruvate decarboxylase and thus reducing feedback inhibition of pyruvate kinase.

A

FALSE; PYRUVATE DECARBOXYLASE DOES NOT OCCUR IN THE LIVER!!!

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24
Q

T/F Hexokinase is the primary enzyme in liver that converts glucose to glucose-6-P

A

FALSE; Hexokinase does NOT occur in the liver, that is GLUCOKINASE

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25
What is the sixth step of glycolysis, and which enzyme catalyzes the reaction?
oxidation of GAP to 1,3-bisphosphoglycerate. This step is catalyzed by **glyceraldehyde-3-phosphate dehydrogenase** and involves the reduction of NAD+ to NADH
26
What occurs during the seventh step of glycolysis, and what enzyme is responsible?
1,3-bisphosphoglycerate is converted into 3-phosphoglycerate. The enzyme **phosphoglycerate kinase** catalyzes this reaction, which generates ATP from ADP.
27
What enzyme catalyzes the eighth step of glycolysis, and what is the product?
The eighth step involves the conversion of 3-phosphoglycerate to 2-phosphoglycerate. The enzyme responsible is **phosphoglycerate mutase.**
28
Describe the ninth step of glycolysis and the enzyme involved.
The ninth step is the dehydration of 2-phosphoglycerate to phosphoenolpyruvate (PEP). The enzyme involved is **enolase**
29
What is the final step of glycolysis, and which enzyme catalyzes it?
conversion of phosphoenolpyruvate (PEP) to pyruvate. This step is catalyzed by **pyruvate kinase** and results in the production of ATP.
30
Compare Hexokinase vs Glucokinase in terms of: usage, location, Km, capacity, mechanism, and how much glucose it takes
**usage** Hexokinase: Gluc. Fruct. or Mannose Glucokinase: Glucose ONLY **location** Hex: typical cell Gluc: Liver **Km** Hex: 0.1 mM Gluc: 10 mM portal vein: 5 mM **capacity** Hex: Low capacity Gluc: High capacity **mechanism** Hex: Direct feedback regulation by G6P Gluc: Diff. regulatory mechanism (after G6P goes to glycogen n fat) **how much?** Hex: v. polite! takes only as much glucose as needed Gluc: Stores excess gluc, but doesn't compete w/ other tissues
31
What carbons from Fructose-1,6-bisphosphate turn into DHAP and GAP
C4=C3 C5=C2 C6=C1
32
Why is pyruvate kinase named that way?
Even though it is irreversible (in vivo), it can still go the opposite direction ONLY **in vitro**. So it is the enzyme named for reverse reaction (that doesn't occur in living cells)
33
Lactate Dehydrogenase
reduces pyruvate to lactate using NADH -reversible
34
Hexokinase/Glucokinase (allosteric regulation)
✮ Glucose 6 phosphate inhibits Hexo ✬ Fructose 6 phosphate inhibits Gluco
35
Phosphofructokinase-1 (PFK-1) (allosteric regulation)
**Activated by:** ❁AMP: Signals low energy status, promoting glycolysis. ❁Fructose-2,6-bisphosphate **Inhibited by:** ❁ATP: Indicates high energy status, slowing down glycolysis. ❁Citrate: Reflects a high level of TCA cycle intermediates, reducing glycolysis. (found in mitochondria!!)
36
Pyruvate Kinase (allosteric regulation)
**Activated by:** ✪Fructose-1,6-bisphosphate ✪ AMP **Inhibited by:** ✪ATP: Indicates sufficient energy levels. ✪Alanine: A building block for protein synthesis, suggesting that resources should be diverted from glycolysis. ✪ Acetyl-CoA
37
Aerobic vs Anaerobic Glucose Metabolism
**Aerobic** Gluc--> 6 CO2 ATP gluc ≈ 38 Max flux: 1 Max Energy Output: 38 **Anaerobic** Gluc--> 2 lactate ATP gluc = 2 Max flux: 100 Max energy Output: 200 ** ≈3 ATP/ Gluc if starting from Glycogen
38
What is going on in your muscles vs liver when you're running for your life?
Muscles (can be anaerobic): Is doing *Glycolysis* ☞Glycogen➙ Gluc (➙G6P) ➙ Pyruvate ➙Lactate Liver (Aerobic): is doing *Gluconeogenesis* ☞ Lactate ➙ Pyruvate➙ Gluc ➙Glycogen (liver then pulls lactic acid levels down)
39
When running for life, an enzyme like PFK1 would be turned on or off in muscles/ liver?
muscles: ON liver: OFF (don't want to do glycolysis)
40
Draw lactate fermentation mechanism
slide 53 of lec 2
41
What is the disease name of TPP deficiency? Name the vitamin and the people who get it
*BeriBeri *Vitamin B1 *People who eat only white rice and alcoholics
42
Draw the Thiazolium ring of TTP
slide 58 of lec 2
43
Do humans have PDC?; why or why not?
NO; bc if we did this, we would have a hangover after we worked out (acetylaldehyde is why we have hangovers) **Vigorous exercise ⥇ Ethanol ** Acetaldehyde is toxic
44
Do humans have Alcohol Dehydrogenase?
YES!! (reversible) ➥ can turn ethanol into acetaldehyde ➤ Destroys ethanol made by intestinal bacteria ➤ Exogenous EtOH → **acetaldehyde** → hangover ➤ form of ADH partially determines susceptibility to aerodigestive cancers
45
What drug inhibits the reaction of Acetaldehyde⇢Acetate? Why would you want to do that?
disulfiram "Antabuse". This is used to treat alcoholism, as it gives you a massive hangover
46
____is a competitive inhibitor of ADH ____ is a competitive inhibitor of Ethylene Glycol (antifreeze)
*Fomepizole * Ethanol
47
PET scans use___
2'-[¹⁸F] fluoro-2-deoxyglucose → Glucose analog that can be phosphorylated but not further metabolized → ¹⁸F decays by omitting a positron
48
In liver, Fructokinase converts:
Fructose + ATP → F**1**P +Pi
49
What enzyme is used in the reaction 1.Ethanol⇢Acetaldehyde and 2.Acetaldehyde⇢Acetate? where are they found?
1. Alcohol Dehydrogenase (Cytosol) 2. Acetaldehyde Dehydrogenase (Acetate)
50
Warburg effect
Cancer cells oftern convert glucose☞lactate instead of oxidative phosphorylation even when oxygen is present
51
lactate DH function
reduces pyruvate to lactate using NADH reversible cori cycle
52
What symptoms come from TTP (Vit B1) deficinecy?
*Pain *Paralysis *Wasting *Heart Failure
53
✦What is the function of PFK-2 in the regulation of F6P and F2,6BP? ✧What is the function of F2,6BPase in the regulation of F6P and F2,6BP?
✦PFK-2 catalyzes the conversion of F6P to F2,6BP. ✧F2,6BPase catalyzes the conversion of F2,6BP back to F6P.
54
In an anabolic pathway, where do you get the energy you need to proceed the reaction
NADPH
55
what is the reaction that occurs between NAD+ and NADH ?
dehydrogenase reaction
56
pyruvate decarboxylase requires
thiamine pyrophosphate (TPP)
57
Hexokinase/Glucokinase (*hormonal regulation*)
✦ **insulin** stimulates/ activates HK & GK (indicates high blood glucose levels) ✧ **Glucagon** inhibits HK & GK (indicates low blood glucose levels)
58
Phosphofructokinase (*Hormonal regulation*)
✦ ** insulin** *stimulates* PFK II & *inhibits* F2,6BPase (glycolysis) ✧ **Glucagon** *stimulates* F2,6BPase and *inhibits* PFKII (GNG)
59
Pyruvate Kinase (*Hormonal regulation*)
✦ Insulin stimulates (dephosphorylase of PK) ✧ Glucagon inhibits (by phosphorylation of PK)
60
in ___, fructokinase converts:
liver; Fructose + ATP➔ F1P + Pi
61
Draw fructose metabolism
lec 2, slide 81
62
phosphofructokinase (PFK1) is also strongly activated by___? explain how
F2-6,BP PFK-2 is responsible for the production of (F2,6BP), which is a potent allosteric activator of PFK-1. F2,6BP enhances the activity of PFK-1, thus stimulating glycolysis, and it inhibits the enzyme F1,6-BPase, which is involved in gluconeogenesis (PFK2 --activates--> F2,6BP--activates--> PFK1 ➥ inhibits F1,6BPase (F1,6BP is a product of it)
63
What enzyme is deficient in Johnny, causing him to dislike sweets?
Johnny has a deficiency in fructose-1-phosphate aldolase (F1P aldolase), also known as aldolase B.
64
What happens to fructose in Johnny’s body due to the lack of F1P aldolase?
Fructose is converted into fructose-1-phosphate (F1P), which accumulates due to the lack of F1P aldolase
65
How does the accumulation of F1P affect ATP and AMP levels? (why Johnny may not like sweets)
The accumulation of F1P leads to depletion of Pi, which reduces ATP production and increases AMP levels.
66
What effect does increased AMP and decreased ATP have on glycolysis? (johnny n sweets)
Increased AMP and decreased ATP stimulate glycolysis, leading to increased production of pyruvate and lactate, causing lactic acidosis.
67
How does the buildup of F1P affect blood glucose levels?
The depletion of Pi blocks glycogen breakdown, leading to low blood glucose levels (hypoglycemia).
68
What long-term effects can occur due to F1P accumulation in the body? (johnny n sweets)
Over time, the accumulation of F1P and associated metabolic disruptions can lead to liver and kidney damage, and in extreme cases, it can be fatal
69
What metabolic product causes Johnny to feel unwell after consuming sweets?
Johnny feels unwell because of the accumulation of lactate, which leads to lactic acidosis and a drop in blood pH.
70
Why is Pi depletion significant in Johnny’s metabolic disturbance?
Pi depletion limits ATP synthesis and blocks glycogen breakdown (glycogen → G1P), causing energy imbalances and low blood glucose.
71
How does fructose-1-phosphate (F1P) affect glucose metabolism?
Fructose-1-phosphate (F1P) facilitates glucose uptake by activating glucokinase, enhancing glucose's entry into glycolysis.
72
What are the downstream products of fructose metabolism that are rapidly produced due to the bypass of PFK-1? Answer:
Pyruvate and lactate are the downstream products rapidly produced due to the bypass of PFK-1.
73
What role does insulin play in fructose metabolism?
Insulin activates some glycolytic enzymes, enhancing glucose metabolism, but fructose largely bypasses these regulatory effects due to its detour around PFK-1.
73
How does fructose metabolism contribute to fat production?
Fructose metabolism increases pyruvate production, which is converted to acetyl-CoA. Excess acetyl-CoA is diverted to fatty acid synthesis, contributing to fat buildup.
74
Draw Galactose metabolism
Lec 2, slide 89
75
Galactosemia
*Galactokinase deficiency * buildup Gal→ galactinol→ cataracts
76
GAL-1-P uridylyl transferase deficiency
❆ Gal-1-P→ toxic byproducts ❆ cataracts, liver damage, mental retardation ❆ can be fatal even on low gal diet
77
UDP-4-epimerase deficiency
✭ Gal-1-P & UDG Gal → toxic byproducts ✭ cataracts, liver damage, mental retardation ✭ less severe with low gal diet
78
draw mannose mechanism and explain what is happening
lec 2, slide 92 *Mannose, which differs from glucose in stereochemistry at carbon 2, is converted to mannose-6-P by hexokinase and then to F6P by an isomerase
79
T/F; glycerol can also enter glycolysis pathway? explain how or how not
*Glycerol is produced in substantial amounts during degradation ➥ **Glycerol kinase (*liver*)** * Glycerol + ATP → Glycerol-3P + ADP – Irreversible ➥ **Glycerol-3P DH** * Glycerol-3P + NAD+ → DHAP + NADH
80
Draw the Pentose Phosphate Pathway
Lec 2, slide 95
81
T/F, the top section of PPP makes 2 NADH
FALSE; it makes 2 NAD**P**H G6P→ 5C sugar-P
82
bottom section interconverts 3what type of sugars?
3C-7C sugars; NOT 2
83
The top part of PPP is ____, while the bottom section is____.
irreversible (only operates when cell needs to make NADPH); reversible
84
How does NADH and NADPH differ?
NADH: * mainly in oxidized form (NAD+) * removes 2 e- during “fuel” metabolism NADPH: * mainly in reduced form (NADPH instead of NADP+) * adds 2e- during biosynthesis & detox of free radicals
85
G6PDH is ____ and inhibited by high concentrations of____? *what does G6P--> 6-phosphogluconolactone look like?
**irreversible; NAD**P**H *ring form of aldehyde⇨ ring form of carboxylic acid=lactone
86
T/F you should put fructose on an IV drip for better hydration
FALSE; fructose is primarily metabolized on the liver, and rapid or excessive fructose infusion can overwhelm the liver's metabolic capacity.
87
T/F; hydrolysis of lactone occurs only enzymatically
FALSE; it occurs both enzymatically and non enzimatically
88
T/F, 3 to 7 carbon sugars on PPP can be reversibly inter-converted without any pieces left over.
TRUE! 2 carbon metabolism is different
89
how is xylulose similar to fructose in PPP?
C#2 of xylulose has =O and -OH of C#3 is "flipped to the other side" just like in fructose
90
How does NADPH acts as an antioxidant?
* Inactivates peroxides etc. * Reduces free radical damage
91
G6P DH is a major source of ??? ✦ what are the results of inactive G6P DH?
NADPH ✧Inactive G6P DH: * ↑↑ peroxides * Lipid and protein damage * RBC lysis etc. * Embryo death
92
How does G6PD deficiency affect sensitivity to free radicals?
G6PD deficiency increases sensitivity to free radicals, especially from sources like fava beans and antimalarial drugs (such as primaquine), which lead to increased peroxide levels.
93
What is the consequence of increased peroxide levels in people with G6PD deficiency?
Increased peroxide levels can lead to red blood cell lysis, resulting in anemia.
94
Is anemia caused by G6PD deficiency permanent?
No, the anemia is transient; the body eventually produces new red blood cells with higher G6PD levels.
95
Where is G6PD deficiency most common, and why?
G6PD deficiency is most common in regions where malaria is endemic, such as the Middle East and Africa. The deficiency offers partial protection against malaria, which provides a selective advantage in these areas.
96
Xyl5P also activates___ in___?
PFK**2** in liver ➥ after high carb meal Pentose P pathway backs up ↑Xyl5P ↑F2,6BP ↑glycolysis ↑ Acetyl-CoA ↑FAT synthesis
97
Why do cancer cells require large amounts of NADPH?
Cancer cells require large amounts of NADPH to fuel their anabolic processes, neutralize oxidative stress, synthesize essential biomolecules, and maintain rapid proliferation. NADPH supports both biosynthetic needs and antioxidant defense mechanisms, enabling cancer cells to thrive under conditions that would normally be harmful to regular cells
98
Which tumor suppressor inhibits G6P DH in cancer cells?
p53
99
What additional action does p53 have in relation to glycolysis?
p53 increases levels of TIGAR (an enzyme that acts as an F2,6BPase), reducing glycolysis.
100
How does TIGAR affect glycolysis and the Warburg effect?
Answer: TIGAR reduces the level of F2,6BP, which decreases glycolysis, thus inhibiting the Warburg effect.
101
Why are glycogen and gluconeogenesis important for maintaining blood glucose levels?
Glycogen stores and gluconeogenesis are essential because humans use approximately **160 grams of glucose per day**, with the brain consuming **75%**. Glycogen provides a reservoir of glucose, and gluconeogenesis in the liver and kidneys ensures glucose availability during fasting or low-carb diets.
102
How much glucose can the human body store in glycogen and body fluids?
The body fluids contain about 20 grams of glucose, while glycogen stores can provide 180-200 grams.
103
What is the role of glycogen in the liver during fasting or exercise?
The liver stores glycogen to maintain stable blood glucose levels (~5mM). During fasting or exercise, glycogen is broken down to provide glucose for the brain and other organs.
104
How to get glucose if you are starving or on a low carb diet?
Fatty acids, but you get little if any glucose Protein→ amino acids → pyruvate et. al → glucose lactic acid → glucose
105
What happens in muscle during strenuous exercise in terms of glycogen metabolism?
Muscles break down their glycogen stores (1-2% glycogen) to quickly mobilize glucose for energy during fight or flight responses or strenuous exercise
106
How is the liver in terms of Glycogen metabolism?
**Liver**: up to 10% glycogen ❁ maintain ≈5 mM blood glucose ∼ brain normally uses only glucose (<2mM → pass out) ❁Liver has ≈ 16-hour supply of glucose ∼Supplement with gluconeogenesis * Amino acids → glucose * Fatty acids → little if any glucose
107
where is brain glycogen mainly stored?
astrocytes
108
How is glycogen in the brain different from glycogen in the liver and muscle?
Glycogen in the brain is rapidly mobilized in oxygen-limited conditions, such as during hypoxia, and it is often not detected because of its rapid use
109
What role does glycogen in astrocytes play in the brain? Answer:
Glycogen in astrocytes helps the brain cope with hypoxia and is also involved in processes like learning and memory.
110
How does glycogen accumulate and mobilize in the brain compared to the liver?
Glycogen levels near neurons decrease while awake and increase during sleep. But during the day when you're eating, glycogen levels rise in liver, whilr go down at night, bc you're releasing glucose
111
Why does brain glycogen play an important role despite being present in small amounts?
Even in small amounts, brain glycogen is important because it provides rapid energy under stress conditions (e.g., hypoxia) and supports cognitive functions like learning and memory.
112
describe the glycogen structure
▶︎has ONE reducing end ▶︎MULTIPLE non reducing ends branched ▶︎12 concentric shel
113
What enzyme is responsible for breaking down glycogen, and what does it produce?
Glycogen phosphorylase is responsible for breaking down glycogen, and it produces glucose-1-phosphate (G1P).
114
What cofactor does glycogen phosphorylase require for its activity?
Vitamin B6 (pyridoxal phosphate) for its activity.
115
How does glycogen phosphorylase remove glucose units from glycogen?
Glycogen phosphorylase removes one glucose unit at a time from the **non-reducing** end of glycogen, provided it is at least 5 units away from a branch point.
116
What is the advantage of using inorganic phosphate (Pi) in the cleavage reaction catalyzed by glycogen phosphorylase?
Using inorganic phosphate (Pi) for cleavage saves ATP because it directly produces G1P instead of requiring an additional phosphorylation step.
117
Why is water excluded from the active site of glycogen phosphorylase?
Water is excluded from the active site to prevent hydrolysis of the glycogen chain, ensuring that glucose is released as G1P instead of free glucose.
118
How is glycogen phosphorylase regulated?
Glycogen phosphorylase is regulated through allosteric regulation and covalent modification. Allosteric effectors like G6P and AMP shift its equilibrium between the T (inactive) and R (active) states. Hormones also regulate it via phosphorylation.
119
What is the role of the debranching enzyme in glycogen metabolism?
The debranching enzyme transfers all but the last glucose unit from a branch to a nearby non-reducing end. It also cleaves the α-1,6 bond of the remaining glucose, releasing it as free glucose.
120
The **debranching** cleaves at ___ bonds while the **branching** cleaves at___
debranching:
121
What is the overall yield of glucose types when glycogen is broken down?
Approximately 90% of the glucose released from glycogen is in the form of G1P, while about 10% is released as free glucose from branch points
122
Why can’t glycogen phosphorylase remove glucose units close to branch points?
Glycogen phosphorylase cannot remove glucose units that are closer than 5 units from a branch because its structure restricts access to glucose residues near the branch point.
123
Will the debranching enzyme cleave to G-1-P?
no!, bc it's not down at the bottom of the hole to be protected
124
Phosphoglucomutase in terms of glycogen metabolism
✷ G1P⇒G6P ✷ REVERSIBLE ✷ Phosphoglucomutase catalyzes the reversible conversion between glucose-1-phosphate (G1P) and glucose-6-phosphate (G6P). ✷During glycogenolysis (glycogen breakdown), G1P (produced from glycogen by glycogen phosphorylase) is converted into G6P, which can then enter glycolysis for energy production or be dephosphorylated to free glucose in the liver. During glycogenesis (glycogen synthesis), G6P is converted into G1P, which is then activated to UDP-glucose for incorporation into glycogen.
125
How do glycogen phosphorylase and the debranching enzyme work together during glycogen breakdown?
❁Glycogen Phosphorylase initiates glycogen breakdown by cleaving α-1,4 glycosidic bonds at the non-reducing ends of glycogen, releasing glucose-1-phosphate (G1P). It continues this process until it reaches a point 4 glucose residues away from a branch point (α-1,6 linkage). ❁At this point, glycogen phosphorylase cannot proceed further, and the debranching enzyme takes over. The debranching enzyme has two activities: ☞Transferase Activity: It transfers a block of 3 glucose residues from the branch to a nearby non-reducing end, forming a new α-1,4 linkage. ☞Glucosidase Activity: It then cleaves the remaining single glucose unit attached by the α-1,6 bond, releasing it as free glucose.
126
G6Pase
✴︎ liver ONLY ✴︎ G6P ➔ Gluc + Pi ✴︎ irreversible ✴︎ high Km ✴︎ allows excess glucose from glycogen breakdown or gluconeogenesis to enter the blood stream (for brain etc)
127
What are the effects of G6Pase deficiency ?
In **Von Gierke’s disease**, individuals can store glycogen but cannot release glucose into the bloodstream. This leads to hypoglycemia (low blood glucose), requiring frequent feeding or continuous feeding via IV or gastric tube
128
What are the effects of liver glycogen phosphorylase deficiency?
✷ **Hers' disease** ☞ Difficult in mobilizing liver glycogen ∼Hypoglycemia solution: ☞ frequent feeding ☞surgical transposition of portal vein
129
What happens in muscle glycogen phosphorylase deficiency ?
In **McArdle’s disease**, individuals have difficulty mobilizing muscle glycogen, leading to painful cramps during strenuous exercise.
130
What happens if you have a debranching enzyme deficiency?
✴︎**Cori's disease** ✴︎ Can only mobilize glucose from ends of outer layer of glycogen ( can mobilize part of it but not all of it) → frequent feeding → high protein diet
131
What are the key regulatory enzymes in glycogen metabolism?
✴︎glycogen phosphorylase, which breaks down glycogen, and ✴︎glycogen synthase, which synthesizes glycogen. These enzymes are regulated by allosteric factors and covalent modification.
132
What enzyme catalyzes the rate-limiting step of gluconeogenesis, converting fructose-1,6-bisphosphate to fructose-6-phosphate?
The enzyme is fructose-1,6-bisphosphatase (F1,6BPase), which is allosterically regulated by AMP and fructose-2,6-bisphosphate (F2,6BP).
133
What is the role of UDP-glucose pyrophosphorylase in glycogen synthesis?
UDP-glucose pyrophosphorylase converts glucose-1-phosphate (G1P) and UTP into UDP-glucose (UDP-G) and pyrophosphate (PPi)
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How is the reaction catalyzed by UDP-glucose pyrophosphorylase made irreversible?
The reaction is made irreversible by the hydrolysis of PPi to 2 Pi by the enzyme inorganic pyrophosphatase, which provides additional energy to drive the reaction forward.
135
How many phosphate groups are involved in the formation of UDP-glucose?
Four phosphate groups are involved (three from UTP and one from G1P).
136
Does glycogen synthesis directly require ATP in this step involving UDP-glucose?
No, ATP is not directly required in this step; instead, UTP is used to form UDP-glucose.
137
Which enzymes are involved in glycogen degradation?
Glycogen phosphorylase removes glucose units from glycogen, and the debranching enzyme helps break down the branch points
138
What is the role of phosphoglucomutase in glycogen metabolism?
Phosphoglucomutase converts glucose-1-phosphate (G1P) into glucose-6-phosphate (G6P), which can enter glycolysis or other metabolic pathways.
139
Why is the hydrolysis of PPi to 2 Pi important in glycogen metabolism?
The hydrolysis of PPi to 2 Pi by inorganic pyrophosphatase ensures that the synthesis of UDP-glucose is irreversible, making the glycogen synthesis pathway energetically favorable.
140
Why is the formation of UDP-glucose considered to have a high-energy bond, and how does it drive glycogen synthesis?
The formation of UDP-glucose involves a **high-energy phosphoester bond** between the **UDP (uridine diphosphate)** and **glucose**. This bond is considered high-energy because when it is cleaved, it releases enough energy to drive the addition of glucose to the growing glycogen chain. The energy released from breaking this bond makes the transfer of glucose by glycogen synthase to the glycogen molecule thermodynamically favorable, allowing glycogen synthesis to proceed.
141
Glycogen synthase is____ under physiological conditions and adds to ____end
irreversible; nonreducing (C#4)
142
Glycogen synthesis requires a primer, which is___
Glycogenin. ➥ Glycogenin is a self-glucosylating protein that serves as the core primer for glycogen synthesis. It has an attached tyrosine residue that catalyzes the attachment of the first glucose molecule from UDP-glucose to itself
143
What are the effects of liver glycogen *synthase* deficiency?
✧little if any glycogen in liver ➥ ↑↑↑ blood sugar after eating ✧ low blood sugar at other times, usually early death
144
Branching enzyme deficiency
**Anderson's disease** ➥ normal amount of glycogen ➥ long unbranched chains ‣ low availability (less nonreducing ends) ‣ low solubility ‣autoimmune attack ‣ few survive past age 4
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Glycogen phosphorylase and synthase in terms of allosteric regulation:
**Glycogen synthase** ➥ ➕ G6P **Glycogen phosphorylase** ➥➕ AMP ➥➖ ATP ➥➖ G6P ➥➖ Gluc
146
what happens if there is excess sugar and energy vs low sugar and high energy demand in terms of *G6P, *ATP, *AMP?
excess sugar and energy: ↑ G6P, ↑ATP, ↓ AMP → make GLYCOGEN low sugar & high energy demand: ↓ G6P, ↓ATP, ↑AMP → break glycogen down
147
148
How does epinephrine (adrenaline) affect glycogen metabolism?
Epinephrine increases cAMP levels, activating glycogen phosphorylase to mobilize glycogen and release glucose for energy during the "fight or flight" response.
149
What role does glucagon play in glycogen metabolism?
Glucagon is released during low blood sugar levels, increasing cAMP in the liver, which activates glycogen phosphorylase to break down glycogen and release glucose into the bloodstream, especially to supply the brain
150
How does insulin regulate glycogen metabolism?
Insulin is released during **high blood sugar levels** and works by **decreasing cAMP levels**, which promotes the activation of **glycogen synthase** to store glucose as glycogen and inhibit glycogen breakdown.
151
What is the effect of increased cAMP in glycogen metabolism?
Increased cAMP leads to the activation of protein kinase A (PKA), which activates glycogen phosphorylase and stimulates glycogen breakdown.
152
How does the hormonal regulation of glycogen metabolism differ between epinephrine/glucagon and insulin?
Epinephrine and **glucagon** increase cAMP,(in liver) leading to glycogen breakdown (mobilization), while the pancreas secretes **insulin**, which decreases cAMP, promoting glycogen synthesis storage ****IN LIVER!!!****
153
Draw gluconeogenesis
lec 2, slide 37
154
F1,6BPase opposes____ how?
**PFK1** *F1,6BPase:* ➖ AMP ➕ ATP ➕ citrate ➖ F2,6P *PFK1* ➕ AMP ➖ ATP ➖ citrate ➕ F2,6P
154
What enzymes differ in glycolysis vs gluconeogensis?
**Glucose → Glucose-6-phosphate** *Glycolysisis*: Hexokinase/Glucokinase: *GLuconeogenesis*: Glucose-6-phosphatase **Fructose-6-phosphate → Fructose-1,6-bisphosphate** *Glycolysis*: (PFK-1) *Gluconeogenesis*:Fructose-1,6-bisphosphatase **Phosphoenolpyruvate → Pyruvate** *Glycolysis*: Pyruvate kinase *Gluconeogenesis*:Pyruvate carboxylase & PEPCK
155
Pyruvate Carboxylase ONLY happens in:
The mitochondria
156
What is the role of pyruvate carboxylase in gluconeogenesis?
✴︎Pyruvate carboxylase converts pyruvate into oxaloacetate (OAA) in the mitochondria, ✴︎This enzyme is activated by acetyl-CoA. ✴︎ Irreversible ✴︎ Requires biotin
157
Pyruvate requires ___, which is vitamin___. This vitamin serves as a ____. ➥ explain how
biotin; B7; mobile CO2 carrier ➥Pyruvate carboxylase uses ATP to load CO2 onto biotin and then delivers it to pyruvate.
158
What enzyme converts oxaloacetate (OAA) to phosphoenolpyruvate (PEP) in gluconeogenesis?
phosphoenolpyruvate carboxykinase (PEPCK)
159
T/F; PEPCK uses ATP as its main energy source
FALSE!; PEPCK uses GTP (guanosine triphosphate) rather than ATP to convert oxaloacetate to phosphoenolpyruvate.
160
Where does the conversion of pyruvate to oxaloacetate (OAA) occur in gluconeogenesis? and then Where does the majority of gluconeogenesis occur after OAA is formed?
The conversion of pyruvate to oxaloacetate (OAA) occurs in the mitochondria. The majority of gluconeogenesis occurs in the cytoplasm, where OAA is eventually converted to glucose.
161
Why is there a problem with OAA transport during gluconeogenesis? ➥ and how does the cell solve this problem?
The problem is that OAA cannot directly cross the mitochondrial membrane to reach the cytoplasm where gluconeogenesis continues ➥ The cell converts OAA to malate or aspartate within the mitochondria. These molecules can cross the mitochondrial membrane, and once in the cytoplasm, they are converted back to OAA.
162
Why is NADH needed in the cytoplasm for gluconeogenesis?
NADH is needed in the cytoplasm for the reduction step of converting 1,3-bisphosphoglycerate to glyceraldehyde-3-phosphate during gluconeogenesis.
163
Where is most NADH produced in the cell?
Most NADH is produced in the mitochondria during processes such as the citric acid cycle and beta-oxidation.
164
How does the cell solve the problem of needing NADH in the cytoplasm for gluconeogenesis?
The cell uses the malate shuttle: OAA is converted to malate, which carries the reducing equivalents (NADH) across the mitochondrial membrane. In the cytoplasm, malate is converted back to OAA, regenerating NADH in the process.
165
Can you explain how liver responds to low blood glucose? (cascade of events)
low blood glucose ➥ INC. glucagon secretion ➥ INC. cAMP ➥ INC. enzyme phosphorylation ➥ *activation* of FBPase-2 and *inactivation* of PFK2 ➥ Decreased **f2,6P** ➥ *inhibition* of PFK and *activation* of FBPase ➥ INC gluconeogenesis
166
167
Draw the Pyruvate DH rxn is it reversible or irreversible?
Pyruvate + CoA + NAD+ → Acetyl-CoA + CO2 + NADH **Irreversible
168
What does pyruvate DH require?
- TTP (Vitamin B1) - FAD/ FADH ( Vit. B2) - NAD/ NADH ( vit. B3) - Acetyl-CoA (Vit. B5) - Lipoic acid
169
what is the most important molecule that fuels the TCA cycle
acetyl CoA
170
where does the TCA cycle occur
mitochondrial matrix
171
In pyruvate DH rxn, hydroxyethyl-TTP transfers H3C-(C=O) to...?
lipoic acid
172
Draw TCA cycle
lec 4; slide 4
173
T/F humans make an excess amount of lipoic acid, so our body has to do a different mechanism to get rid of the excess.
FALSE!!; humans can't make lipoic acid, ie it is a **vitamin**
174
What are these compounds? -OOC-CH2-CH2-(C=O)-COOOOC-CH2-CH2-COO- -OOC-CH2-(C=O)-COO- -OOC-CH2-HCOH-COO- -OOC-CH=CH-COO
a-KG succinate oxaloacetate malate fumarate
175
Which enzymes in the TCA cycle: *release CO2 *require FAD or NAD or lipoic acid, *are inhibited by arsenic *produce isocitrate or fumarate or αKG or OXAC *use Acetyl-CoA as a substrate *use GTP as a substrate
**Release CO₂?** ★Isocitrate dehydrogenase (converts isocitrate to α-ketoglutarate) ★α-Ketoglutarate dehydrogenase (converts α-ketoglutarate to succinyl-CoA) **Require FAD, NAD, or lipoic acid and are inhibited by arsenic?** ★α-Ketoglutarate dehydrogenase complex requires NAD and lipoic acid and is inhibited by arsenic. ★Succinate dehydrogenase requires FAD but is not directly affected by arsenic. **Produce isocitrate, fumarate, α-ketoglutarate, or oxaloacetate (OAA)?** ★Citrate synthase produces citrate, which converts to isocitrate. ★Aconitase rearranges citrate into isocitrate. ★Isocitrate dehydrogenase converts isocitrate into α-ketoglutarate. ★Succinate dehydrogenase produces fumarate. ★Malate dehydrogenase converts malate to oxaloacetate. **Use Acetyl-CoA as a substrate?** *Citrate synthase* is the enzyme that uses acetyl-CoA and oxaloacetate to form citrate. **Use GTP as a substrate?** ★Succinyl-CoA synthetase uses GTP in the conversion of succinyl-CoA to succinate.
176
List the reversible vs irreversible enzymes in TCA cycle
**Irreversible** ✧Citrate Synthase ✧Isocitrate Dehydrogenase ( 1st NADH) ✧α-Ketoglutarate Dehydrogenase ( 2nd NADH) **Irreversible** ✦Aconitase ✦Succinyl-CoA Synthetase (Succinyl-CoA Thiokinase) ✦Succinate Dehydrogenase ✦Fumarase ✦Malate Dehydrogenase
177
Citrate synthase is fueled by?
Thioester bonds
178
𝛼-KG DH has the same enzymatic mechanism and cofactors as____ the cofactors being...
**pyruvate DH** ➥ TPP ➥ H-S-CoA ➥ Lipoic acid ➥ NAD+ ➥ FAD
179
Succinyl-CoA synthetase harvests high energy thioester bond to...
GTP
180
Succinate DH uses ___→___
FAD → FADH2 bc FADH2 has less energy than NADH
181
T/F; fumarase rxn is a hydration rxn, not a redox rxn
TRUE; converts fumarate → malate by adding water. (no NADH NADH or FADH2)
182
TCA cycle regulation
➖ NADH ➖ ATP ➕ Ca 2+ (muscle contraction)
183
low levels of TCA cycle intermediates would also cause:
high levels of acetyl-CoA
184
What are some examples of anaplerotic rxns?
✩**Pyruvate Carboxylase Reaction:** Pyruvate + CO₂ + ATP → Oxaloacetate (OAA) + ADP + Pi ✩**Transamination of Glutamate to α-Ketoglutarate:** Reaction: Glutamate ↔ α-Ketoglutarate + NH3 ✩ **Aspartate Transaminase Reaction:** Aspartate + α-Ketoglutarate ↔ Oxaloacetate + Glutamate ✩**Propionyl-CoA to Succinyl-CoA Conversion:** Propionyl-CoA → Succinyl-CoA ✩**Pyruvate to Malate:** Pyruvate + CO₂ + NAD(P)H → Malate + NAD(P)+ ✩PEP ---PEP carboxylase-->oxaloacetate ✩ pyruvate ---malic enzyme--> L-malate
185
Where is the Glyoxylate cycle found?
Plants Bacteria FUNgi **NOT** animals