Ch. 12: CHO Metabolism I: Glycolysis & TCA Cyle Flashcards

1
Q

What are the 2 purely ketogenic a.a.?

A

Leu

Lys

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2
Q

What is the common product all digestion products are metabolized to?

A

Acetyl-CoA

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3
Q

5 fates of glucose?

A

1) convert to glycogen
2) pentose phosphate pathway/HMP shunt
3) glycerol of TG
4) carbon skeleton for a.a.
5) acetyl CoA for FA & cholesterol synthesis

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4
Q

Which a.a. bypass liver and go to tissues?

A

3 branch-chained a.a.

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5
Q

How many ATP are gained aerobically?

A

36-38 ATP

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6
Q

How many ATP are gained anaerobically?

A

2 ATP

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7
Q

Glucose transporters: GLUT-1

Locations? Properties?

A

Brain, microvessels, RBCs, placenta, kidneys, other cells

Low Km, ubiquitous basal transporter

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8
Q

Defect of GLUT 1?

A

Poorly controlled seizures

Delayed development

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9
Q

Glucose transporters: GLUT-2

Locations? Properties?

A

Liver, pancreatic beta cells, small intestine

High Km
Release insulin

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10
Q

Glucose transporters: GLUT-3

Locations? Properties?

A

Brain, placenta, fetal muscle

Low Km
Provide glucose to glucose-dependent tissues

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11
Q

Glucose transporters: GLUT-4

Locations? Properties?

A

Skeletal & heart muscle, fat tissue

Insulin-responsive transporter (insulin causes glut 4 within cells to move to cell membrane)

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12
Q

Glucose transporters: GLUT-5

Locations? Properties?

A

Small intestine, testes

High affinity for fructose

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13
Q

Glucose transporters: SGLT 1 & 2

Locations? Properties?

A
Small intestines, renal tubules (SGLT 1)
Renal tubules (SGLT 2)

Low Km

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14
Q

When will GLUT 2 activate? (Only)

A

Hyperglycemia

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15
Q

Insulin secretion: mechanism

A

⬆️ glu ➡️ ⬆️ATP ➡️ blocks ATP/K+ channel ➡️ membrane depolarization ➡️ ⬆️Ca2 ➡️ insulin secretion

ATP/K+ channel also blocked by sulphonlyurea

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16
Q

Glycolysis:

G3P dehydrogenase catalyzes what step?

What inhibits it?

A

Glyceraldehyde 3-phosphate ➡️ 1,3-bisphosphoglycerate

Iodoacetate

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17
Q

Glycolysis:

Enolase catalyzes what step?

What inhibits it?

A

2-phosphoglycerate ➡️ phosphoenolpyruvate

Fluoride

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18
Q

1st main regulatory point of glycolysis?

Positive modulators? Negative?

A

Hexokinase (glucose ➡️ glucose-6-phosphate)

➕: ATP, Pi

➖: glucose-6-phosphate

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19
Q

2nd main regulatory point of glycolysis?

Positive modulators? Negative?

A

6-phosphofructokinase (fructose-6-phosphate ➡️ fructose-1,6-bisphosphate)

➕: fructose-2,6-bisphosphate, ADP, AMP, Pi, K+, NH4+

➖: ATP, citrate

20
Q

3rd main regulatory point of glycolysis?

Positive modulators? Negative?

A

Pyruvate kinase (phosphoenolpyruvate ➡️ pyruvate)

➕: fructose-1,6-bisphosphate

➖: ATP, acetyl-CoA, alanine

21
Q

Compare Km & Vmax of glucokinase vs hexokinase

A

Glucokinase: ⬆️ Km, ⬆️ Vmax (only active w/hyperglycemia)

Hexokinase: ⬇️ Km, ⬇️ Vmax

22
Q

Muscle: what is key enzyme of glycolysis? Regulation?

A

PFK1

Activated: AMP
Inhibited: ATP, citrate

23
Q

Liver: what are the key enzymes of glycolysis?

A

Glucokinase
PFK1 (activated by F-2,6-P)
Pyruvate kinase

24
Q

Where are hexokinase I, II, III found?

Where is hexokinase IV (glucokinase) found?

A

Extrahepatic tissue

Liver, pancreatic beta cells

25
Q

Fxn of glucokinase: liver?

A

Hyperglycemia: ⬆️ glucokinase levels ➡️ initiates metabolism of glucose, maintain uptake of glucose into hepatocytes

Hypoglycemia: ⬇️ glucokinase levels ➡️ liver provider of glucose

26
Q

Fxn of glucokinase: pancreas?

A

Glucose sensor

Modulates insulin secretion (ATP/K+ channel)

27
Q

RBCs: 1,3-BPG converted to ? Fxn of this product?

A

2,3-BPG

Allosteric modulator of hemoglobin (R shift of O2 curve)

28
Q

In what situation is pyruvate kinase inhibited in liver? Activated?

A

Phosphorylated in liver during fasting (⬆️ glucagon levels)

Fed state

29
Q

4 major pathways of pyruvate metabolism?

A

1) ➡️ lactate (lactate dehydrogenase)
2) ➡️ acetyl CoA (pyruvate dehydrogenase complex)
3) ➡️ oxaloacetate (pyruvate carboxylase)
4) ➡️ alanine (alanine aminotransferase)

30
Q

RBCs: what occurs during low O2?

A

deoxy-Hb binds to transmembrane protein band 3 ➡️ releases glycolysis enzymes ➡️ ATP synthesis

31
Q

RBCs: what occurs during ⬆️ O2?

A

Glycolysis enzymes inactive ➡️ HMP shunt active ➡️ NADPH synthesis (antioxidant, reduces glutathione)

32
Q

How does tissue hypoxia ➡️ lactic acidosis?

A

⬇️ O2 ➡️ ⬇️ ATP ➡️ NADH build-up ➡️ promotes conversion of pyruvate to L-lactate

33
Q

When does D-lactate acidosis occur?

A

Jejunoileal bypass, bowel resection

More nutrients in colon ➡️ Gram + bacteria ferment glucose to D-lactate

34
Q

What are the 2 shuttle systems for moving NADH from cytosol ➡️ mitochondria?

A

G3P shuttle (makes FADH2, 2 ATP)

Malate aspartate shuttle (makes NADH, 3 ATP)

35
Q

What 3 enzymes make up the pyruvate dehydrogenase complex?

A

E1: pyruvate decarboxylase
E2: dihydrolipoyl transacetylase
E3: dihydrolipoyl dehydrogenase

36
Q

What are the 5 co-factors of the pyruvate dehydrogenase complex?

A
TPP (thiamine pyrophosphate)
lipoic acid
FAD
NAD+
CoA
37
Q

PD kinase: inactivates PDH complex, how?

Activated by? Inactivated by?

A

Phosphorylates Ser of PDH

➕: ATP/ADP, NADH/NAD+, acetyl CoA/CoA
➖: pyruvate, dichloroacetate, Ca2+

38
Q

Phospho-PDH phosphatase: reactivates PDH complex

Activated by?

A

⬆️ Ca2+
⬆️ Mg2+
Insulin

39
Q

Impacts of thiamine deficiency?

A

Accumulation of pyruvate & lactate in blood and brain ➡️ impairs cardiovascular, nervous, & GI (needs steady ATP supply)

40
Q

Treatments for abnormalities of PDH complex?

A

Ketogenic diets
Thiamine
Dichloroacetate
Diet with asp & glu (can bypass glycosis, converted to TCA intermediates)

41
Q

Why are organic arsenicals & arsenite toxic to PDH complex?

Other enzyme it inhibits?

A

Binds to SH group of lipoic acid

Alpha-ketoglutarate dehydrogenase

42
Q

What rxn does aconitase catalyze?

What inhibits it?

A

Citrate ➡️ [cis-aconitate] ➡️ isocitrate

Fluoroacetate

43
Q

What amino acids can oxaloacetate be made from?

A

Asp

Asn (deamination ➡️ Asp)

44
Q

Citrate synthase: Activators? Inhibitors?

A

➕: ADP

➖: ATP, NADH, Succinyl CoA, Fatty acyl CoA

45
Q

Isocitrate dehydrogenase: Activators? Inhibitors?

A

➕: ADP, Ca2+

➖: NADH, ATP

46
Q

Alpha-ketoglutarate dehydrogenase complex: Activators? Inhibitors?

A

➕: Ca2+

➖: ATP, GTP, NADH, Succinyl CoA

47
Q

How much ATP produced in TCA cycle?

A

3 NADH = 9 ATP
1 FADH2 = 2 ATP
1 GTP = 1 ATP

12 ATP (per acetyl CoA)