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Biochemistry > Exam 3 November 16 Lecture > Flashcards

Exam 3 November 16 Lecture Flashcards

1
Q

What are the 4 pathways that glucose-6-phosphate can enter?

A
  1. gluconeogenesis (liver)
  2. glycogen synthesis
  3. glycolysis
  4. pentose phosphate pathway
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2
Q

What is an overview of glycogen synthesis and breakdown?

A
  1. the liver and muscles store excess glucose as glycogen for later use
  2. glycogen synthesis and breakdown are tightly regulated
  3. the liver regulates blood glucose levels using glycogen
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3
Q

What is the only organ that can convert glucose-6-phosphate back to glucose?

A

the liver

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4
Q

What enzymes are regulated in glycogen metabolism?

A
  1. glycogen phosphorylase → removes glucose molecules on glycogen
  2. glycogen synthase → puts glucose molecules on glycogen (put on anomeric carbon so that it can form glycosidic bond with other carbons)
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5
Q

What are the allosteric regulators for glycogen synthase and phosphorylase?

A
  • positive regulator of glycogen synthase: glucose-6-phosphate
  • negative regulator of glycogen phosphorylase: ATP, glucose-6-phosphate
  • positive regulator of glycogen phosphorylase: AMP
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6
Q

What happens when there is lots of glucose present?

A

don’t want to release more glucose so it is stored as glycogen

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7
Q

What is glycogenesis and glycogenolysis?

A

glycogenesis is glycogen synthesis and glycogenolysis is glycogen breakdown to make free glucose

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8
Q

What is the difference in glycogenolysis purpose in liver compared to the muscle?

A
  1. liver is the only organ that produces glucose with glucose-6-phosphatase to supply glucose to maintain blood glucose levels and supply glucose to other tissues
  2. muscle and other peripheral tissues use glycogenolysis to supply energy to the cell through glycolysis
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9
Q

How long does glucose generation from glycogen (liver) maintain glucose levels after a meal?

A

many hours after a meal

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10
Q

How does liver glycogen last longer?

A

when some gluconeogenesis contributes to the generation of glucose

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11
Q

Glucose is essential for what?

A

red blood cells and the brain in which neither of them can use blood lipids for energy → human brain uses 40% of all energy in the body, glucose levels can drop quickly without glucose coming from the intestine (diet) or the liver (glycogen or gluconeogenesis)

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12
Q

What does intense muscle activity generate?

A

lactate or alanine which can go to the liver (via the Cori or alanine cycle) for gluconeogenesis

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13
Q

What can be used to regenerate glucose-6-phosphate?

A

pyruvate or lactate in muscle can regenerate glucose-6-phosphate and stored as glycogen → but can’t be released into the blood

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14
Q

During long term fasting, where does gluconeogenesis primarily come from?

A

amino acids from protein breakdown → typically, muscle protein and blood proteins are lost first

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15
Q

What is the pyruvate dehydrogenase complex?

A

catalyzes the conversion of pyruvate to acetyl CoA and is located in the mitochondria → reaction is highly exothermic (large negative ΔG and shortens the metabolite by 1 carbon through CO2) and is irreversible in cells → reactions that produce CO2 cannot be reversed in cells due to very low concentration of anhydrous CO2 in cells

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16
Q

What is the PDH reaction catalyzed by?

A

catalyzed by the PDH complex of many copies of three different functional units → uses 5 different coenzymes in which 4 are derived from vitamins

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17
Q

What are the 5 coenzymes of the PDH complex and what are their functions?

A
  1. thiamine pyrophosphate (TPP) aka E1 → decarboxylation and aldehyde group transfer
  2. lipoic acid aka E2 → carrier of hydrogens or acetyl groups
  3. NADH → electron carrier
  4. FADH2 aka E3 → electron carrier
  5. coenzyme A (CoASH) → acetyl group carrier
18
Q

What are the substrates of the PDH reaction?

A

pyruvate, CoASH, NAD+ (which then gets reduced)

19
Q

What are the products of the PDH reaction?

A

acetyl CoA (carries acyl group from pyruvate on CoA), CO2, and NADH

20
Q

What is the function of coenzyme A?

A

while the β-mercaptoethylamine end can undergo redox to form a disulfide-linked dimer, it primarily acts as an acyl carrier without being oxidized → not a real coenzyme

21
Q

Animals can make all the parts of coenzyme A except for what?

A

the pantothenic acid (vitamin B5)

22
Q

What is acetyl CoA produced from?

A

glucose, fatty acids, and some amino acids

23
Q

What is acetyl CoA?

A

fuel for the TCA cycle and material for fatty acid synthesis and ketogenesis → cannot be used to make glucose

24
Q

What are ketone bodies?

A
  1. water soluble products from lipid oxidation (acetyl-coA) and is produced mostly by the liver during prolonged fasting or on a ketogenic diet (low carbs and high fat)
  2. concentration can be higher than 3 mM in the blood
  3. ketogenesis reduces the need for gluconeogenesis → reduces protein wasting
  4. utilized by many tissues (brain and skeletal muscles) as a fuel
25
Q

What are some examples of ketone bodies?

A

acetone, acetoacetate, and 2-hydroxybutyric acid

26
Q

Where does the synthesis of ketone bodies occur?

A

in the mitochondria → HMG-CoA synthase is expressed at high levels in the mitochondria during prolonged fasting

27
Q

What is the ratio of acetoacetic acid to β-hydroxybutyric acid dependent on?

A

dependent on the ratio of NAD+/NADH in the liver mitochondria

28
Q

When is the spontaneous production of acetone from acetoacetic acid significant?

A

only when the concentration of ketone bodies is very high (ketoacidosis)

29
Q

How are ketone bodies utilized?

A

converted to acetyl-CoA in nonhepatic tissues → acetyl-CoA is used as a fuel in the TCA cycle

30
Q

Why is the liver the only organ that cannot utilize ketone bodies for energy?

A

the liver lacks the enzyme thiophorase (β-ketoacyl-CoA transferase) but it can still make ketone bodies just not utilize them

31
Q

What is ketoacidosis?

A
  1. occurs mostly in type 1 diabetic patients
  2. low insulin levels promote lipolysis in the adipose tissues
  3. the production of an excess amount of ketone bodies drops the pH level of the blood → acidosis
  4. gluconeogenesis and glycogenolysis is stimulated in the liver with high levels of blood glucose
  5. high levels of ketone bodies and glucose spill over to urine → osmotic diuresis and acute dehydration
32
Q

What is the main pathway for acetyl CoA?

A

to go into the TCA cycle to produce CO2

33
Q

What is an overview of the TCA cycle?

A

location: mitochondria
input: acetyl-CoA
output: 2 CO2
energy harvested: 3 NADH, 1 FADH2, 1 GTP (ATP) → NADH and FADH2 used in electron transport
mechanism: 8 intermediates with 8 enzymes

34
Q

How is the TCA cycle regulated?

A

the availability of the intermediates → decrease in the concentrations of the intermediates will slow down the utilization of acetyl CoA and energy production

35
Q

Intermediates in the TCA cycle are critical for what?

A

critical building blocks for gluconeogenesis and amino acid synthesis (neurotransmitters, example is GABA)

36
Q

What are anaplerotic reactions?

A

anaplerotic (“filling up”) reactions supply the TCA cycle intermediates → can generate intermediates (ex. glutamate → α-ketoglutarate)

37
Q

When amino acids are not sufficient (ex. growing cells), what is the main source of TCA cycle intermediates?

A

pyruvate

38
Q

What is the first enzyme in gluconeogenesis?

A

pyruvate carboxylase

39
Q

What is the function of pyruvate carboxylase?

A

catalyzes the most important anaplerotic reaction and is critical for gluconeogenesis → high in both the liver and nervous tissues

40
Q

What happens when there is a pyruvate carboxylase deficiency?

A

severe lactic acidosis or death in infancy → can be treated with Triheptanoin (triglyceride with C7 fatty acid) which is converted to succinyl CoA (intermediate in the TCA cycle) → Triheptanoin is like a prodrug to bypass pyruvate carboxylase deficiency

41
Q

What is the mechanism of Triheptanoin?

A
  1. can be converted to acetyl-CoA and then enter the TCA cycle
  2. can be converted to heptanoic acid then propionyl CoA and then succinyl CoA to enter the TCA cycle
42
Q

What is an overview of glycolysis and the TCA cycle?

A

location: cytosol (glycolysis) and mitochondria (TCA cycle)
input: glucose
output: 6 CO2
energy harvested: 2 ATP, 2 GTP (ATP), 10 NADH, 2 FADH2

Biochemistry (18 decks)

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