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

Question 1

What are the 2 purely ketogenic a.a.?

Answer 1

Leu

Lys

Question 2

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

Answer 2

Acetyl-CoA

Question 3

5 fates of glucose?

Answer 3

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

Question 4

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

Answer 4

3 branch-chained a.a.

Question 5

How many ATP are gained aerobically?

Answer 5

36-38 ATP

Question 6

How many ATP are gained anaerobically?

Answer 6

2 ATP

Question 7

Glucose transporters: GLUT-1

Locations? Properties?

Answer 7

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

Low Km, ubiquitous basal transporter

Question 8

Defect of GLUT 1?

Answer 8

Poorly controlled seizures

Delayed development

Question 9

Glucose transporters: GLUT-2

Locations? Properties?

Answer 9

Liver, pancreatic beta cells, small intestine

High Km
Release insulin

Question 10

Glucose transporters: GLUT-3

Locations? Properties?

Answer 10

Brain, placenta, fetal muscle

Low Km
Provide glucose to glucose-dependent tissues

Question 11

Glucose transporters: GLUT-4

Locations? Properties?

Answer 11

Skeletal & heart muscle, fat tissue

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

Question 12

Glucose transporters: GLUT-5

Locations? Properties?

Answer 12

Small intestine, testes

High affinity for fructose

Question 13

Glucose transporters: SGLT 1 & 2

Locations? Properties?

Answer 13

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

Low Km

Question 14

When will GLUT 2 activate? (Only)

Answer 14

Hyperglycemia

Question 15

Insulin secretion: mechanism

Answer 15

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

ATP/K+ channel also blocked by sulphonlyurea

Question 16

Glycolysis:

G3P dehydrogenase catalyzes what step?

What inhibits it?

Answer 16

Glyceraldehyde 3-phosphate ➡️ 1,3-bisphosphoglycerate

Iodoacetate

Question 17

Glycolysis:

Enolase catalyzes what step?

What inhibits it?

Answer 17

2-phosphoglycerate ➡️ phosphoenolpyruvate

Fluoride

Question 18

1st main regulatory point of glycolysis?

Positive modulators? Negative?

Answer 18

Hexokinase (glucose ➡️ glucose-6-phosphate)

➕: ATP, Pi

➖: glucose-6-phosphate

Question 19

2nd main regulatory point of glycolysis?

Positive modulators? Negative?

Answer 19

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

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

➖: ATP, citrate

Question 20

3rd main regulatory point of glycolysis?

Positive modulators? Negative?

Answer 20

Pyruvate kinase (phosphoenolpyruvate ➡️ pyruvate)

➕: fructose-1,6-bisphosphate

➖: ATP, acetyl-CoA, alanine

Question 21

Compare Km & Vmax of glucokinase vs hexokinase

Answer 21

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

Hexokinase: ⬇️ Km, ⬇️ Vmax

Question 22

Muscle: what is key enzyme of glycolysis? Regulation?

Answer 22

PFK1

Activated: AMP
Inhibited: ATP, citrate

Question 23

Liver: what are the key enzymes of glycolysis?

Answer 23

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

Question 24

Where are hexokinase I, II, III found?

Where is hexokinase IV (glucokinase) found?

Answer 24

Extrahepatic tissue

Liver, pancreatic beta cells

Question 25

Fxn of glucokinase: liver?

Answer 25

Hyperglycemia: ⬆️ glucokinase levels ➡️ initiates metabolism of glucose, maintain uptake of glucose into hepatocytes Hypoglycemia: ⬇️ glucokinase levels ➡️ liver provider of glucose

Question 26

Fxn of glucokinase: pancreas?

Answer 26

Glucose sensor Modulates insulin secretion (ATP/K+ channel)

Question 27

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

Answer 27

2,3-BPG Allosteric modulator of hemoglobin (R shift of O2 curve)

Question 28

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

Answer 28

Phosphorylated in liver during fasting (⬆️ glucagon levels) Fed state

Question 29

4 major pathways of pyruvate metabolism?

Answer 29

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

Question 30

RBCs: what occurs during low O2?

Answer 30

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

Question 31

RBCs: what occurs during ⬆️ O2?

Answer 31

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

Question 32

How does tissue hypoxia ➡️ lactic acidosis?

Answer 32

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

Question 33

When does D-lactate acidosis occur?

Answer 33

Jejunoileal bypass, bowel resection More nutrients in colon ➡️ Gram + bacteria ferment glucose to D-lactate

Question 34

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

Answer 34

G3P shuttle (makes FADH2, 2 ATP) Malate aspartate shuttle (makes NADH, 3 ATP)

Question 35

What 3 enzymes make up the pyruvate dehydrogenase complex?

Answer 35

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

Question 36

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

Answer 36

``` TPP (thiamine pyrophosphate) lipoic acid FAD NAD+ CoA ```

Question 37

PD kinase: inactivates PDH complex, how? Activated by? Inactivated by?

Answer 37

Phosphorylates Ser of PDH ➕: ATP/ADP, NADH/NAD+, acetyl CoA/CoA ➖: pyruvate, dichloroacetate, Ca2+

Question 38

Phospho-PDH phosphatase: reactivates PDH complex Activated by?

Answer 38

⬆️ Ca2+ ⬆️ Mg2+ Insulin

Question 39

Impacts of thiamine deficiency?

Answer 39

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

Question 40

Treatments for abnormalities of PDH complex?

Answer 40

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

Question 41

Why are organic arsenicals & arsenite toxic to PDH complex? Other enzyme it inhibits?

Answer 41

Binds to SH group of lipoic acid Alpha-ketoglutarate dehydrogenase

Question 42

What rxn does aconitase catalyze? | What inhibits it?

Answer 42

Citrate ➡️ [cis-aconitate] ➡️ isocitrate Fluoroacetate

Question 43

What amino acids can oxaloacetate be made from?

Answer 43

Asp | Asn (deamination ➡️ Asp)

Question 44

Citrate synthase: Activators? Inhibitors?

Answer 44

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

Question 45

Isocitrate dehydrogenase: Activators? Inhibitors?

Answer 45

➕: ADP, Ca2+ ➖: NADH, ATP

Question 46

Alpha-ketoglutarate dehydrogenase complex: Activators? Inhibitors?

Answer 46

➕: Ca2+ ➖: ATP, GTP, NADH, Succinyl CoA

Question 47

How much ATP produced in TCA cycle?

Answer 47

3 NADH = 9 ATP 1 FADH2 = 2 ATP 1 GTP = 1 ATP 12 ATP (per acetyl CoA)