Glucose Metabolism

Question 1

What cell type depends exclusively on glycolysis to generate ATP?

Answer 1

Erythrocytes (RBCs)

Question 2

Glucose is the major monosaccharide utilized in glycolysis, but _________ and ___________ can also be used

Answer 2

Fructose; galactose

Question 3

Glucose is polar, so it cannot cross the plasma membrane. How is it transported into the cell?

Answer 3

It is phosphorylated (becomes glucose 6-phosphate) by hexokinase or glucokinase, thus trapping it in the cell

Question 4

Which glucose transporter is the main transporter in the brain?

Answer 4

GLUT3

Question 5

Which glucose transporter is insulin-dependent, and is found in skeletal muscle, heart, and adipose tissue?

Answer 5

GLUT4

Question 6

Which glucose transporter facilitates the unregulated uptake (independent of insulin) and is localized to the liver?

Answer 6

GLUT2

Question 7

Describe the affinity of GLUT2 for glucose

Answer 7

GLUT2 is localized to the liver, so it has low affinity

Question 8

What pathological condition is related to the GLUT2 receptor in the liver?

Answer 8

Fanconi-Bickel syndrome

Question 9

Which glucose transporter facilitates unregulated glucose transfer, especially in RBCs and the brain. This transporter has high affinity and is saturated at all times

Answer 9

GLUT1

Question 10

Of the 4 glucose transporters, which ones are regulated by insulin?

Answer 10

GLUT2 and GLUT4

Question 11

How does insulin signaling regulate the GLUT4 transporter?

Answer 11

GLUT4 is sequestered in vesicles, when insulin is present it will cause these vesicles to fuse with the cell membrane to enable GLUT4 induced glucose uptake

Question 12

What is the net production of glycolysis?

Answer 12

2 pyruvate
2 ATP
2 NADH

Question 13

What are the 2 potential fates of pyruvate in aerobic fed conditions?

Answer 13

Converted to Acetyl CoA via PDH and enters TCA, fatty acid synthesis

Converted to Alanine via alanine aminotransferase and begins protein synthesis

Question 14

What is the fate of pyruvate in aerobic fasting conditions?

Answer 14

Converted to oxaloacetate via pyruvate carboxylase and enters gluconeogenesis

Question 15

What are the 2 potential fates of pyruvate in anaerobic conditions?

Answer 15

Converted to lactate via lactate dehydrogenase and enters the Cori cycle

Converted to Alanine via alanine aminotransferase and enters gluconeogenesis or urea cycle

Question 16

Glycolysis occurs in the ____________. There are _____ irreversible reactions and three overall phases consisting of investment (_____ ATP), splitting 6-carbon fructose 1,6BP to get ______ and G3P (3-carbon molecules), and payoff (______ ATP) for a total ATP yield of _______.

Answer 16

Cytoplasm
3
2
DHAP
4
2

Question 17

Phosphorylation of glucose to G6P traps it in the cell, and there are two enzymes capable of doing this. What are they and what is the difference between the 2?

Answer 17

Hexokinase - found in all tissues, high affinity for glucose

Glucokinase - found in the liver and pancreatic beta cells, low affinity for glucose

Question 18

What is the rate limiting step of glycolysis?

Answer 18

Phosphorylation of G6P to fructose 1,6BP

Enzyme = phosphofructokinase-1 (PFK1)

Question 19

What intermediate in glycolysis can get shunted to the PPP? What other pathway can it be shunted to?

Answer 19

G6P

Glycogen synthesis/breakdown

Question 20

Describe the “splitting” phase of glycolysis

Answer 20

Cleavage of 6-carbon Fructose 1, 6-BP to produce 3-carbon DHAP and 3-carbon G3P

Enzyme = aldolase

Question 21

Describe the isomerization step of glycolysis

Answer 21

After F1,6BP is split into DHAP and G3P, the two isomeric products interconvert via triose phosphate isomerase

Question 22

What are the 3 irreversible steps of glycolysis?

Answer 22

Glucose –> Glucose 6P

Fructose 6-P –> Fructose 1,6BP (RL)

Phosphonolpyruvate –> pyruvate

Question 23

What enzyme catalyzes the formation of pyruvate from phosphoenolpyruvate in glycolysis?

Answer 23

Pyruvate kinase

Question 24

What effect would AMP or F2,6BP have on PFK in glycolysis?

Answer 24

Activation

Question 25

What effect would ATP and citrate from the TCA cycle have on PFK in glycolysis?

Answer 25

Inhibition

Question 26

In glycolysis, what hormonal conditions activate protein phosphatases, dephosphorylate PFK-2/FBPase-2 (triggers kinase activity), and produces F2,6BP which activates PFK1?

Answer 26

High insulin/low glucagon

Question 27

In glycolysis, what hormonal conditions induce high [cAMP], activate protein kinase A, phosphorylate PFK-2/FBPase2 (triggers phosphorylation activity), and reduce PFK1 activity?

Answer 27

High glucagon/low insulin

Question 28

What effect would F1,6BP have on pyruvate kinase?

Answer 28

Activation

Question 29

What are the 2 inhibitors of pyruvate kinase?

Answer 29

ATP and Ala - PEP will begin gluconeogenesis

Question 30

What is the most common clinical presentation of someone with defective glycolytic enzymes like phosphoglucose isomerase, aldolase A, triose phosphate isomerase, and pyruvate kinase?

Answer 30

Hemolytic anemia RBCs lack mitochondria, so glycolysis is their only mechanism of ATP production. Inactivation of the glycolytic pathway inactivates ATP-dependent ion pumps, disrupting ion gradients and cell viability

Question 31

The majority of diseases caused by defects in glycolytic enzymes are associated with which enzyme specifically?

Answer 31

Pyruvate kinase

Question 32

What condition could elevate Phe in fetal brains and effectively disrupt glycolysis by inhibiting PK?

Answer 32

PKU

Question 33

Which glycolytic disorder is associated with deficient PFK-1, is the least common GSD in humans, and presents as exercise-induced muscle cramps and weakness as well as hemolytic anemia, high bilirubin, and jaundice?

Answer 33

Tarui disease

Question 34

_________ is compensated for by anaerobic glycolysis, which leads to a buildup of lactate and causes lactic acidosis?

Answer 34

Hypoxia

Question 35

Differentiate between type 1 and type 2 diabetes

Answer 35

Type 1: insulin deficiency Type 2: insulin resistance

Question 36

Where does gluconeogenesis occur?

Answer 36

Primarily in the liver, but also in kidneys and small intestine Cytosol and mitochondria

Question 37

The irreversible steps of glycolysis require "bypass" steps in gluconeogenesis. What are the key bypass enzymes corresponding to the following step?: Pyruvate kinase

Answer 37

PEP carboxylase and pyruvate carboxylase

Question 38

The irreversible steps of glycolysis require "bypass" steps in gluconeogenesis. What are the key bypass enzymes corresponding to the following step?: PFK-1

Answer 38

Fructose 1,6 Bisphosphatase

Question 39

The irreversible steps of glycolysis require "bypass" steps in gluconeogenesis. What are the key bypass enzymes corresponding to the following step?: Hexokinase/glucokinase

Answer 39

Glucose 6-phosphatase

Question 40

What is the purpose of the malate shuttle

Answer 40

In gluconeogenesis, pyruvate must be converted to OAA to bypass an irreversible step of glycolysis. OAA is converted to malate, and malate can then exit the mitochondria and be converted back to OAA which can be converted to PEP

Question 41

What is the rate limiting step of gluconeogenesis?

Answer 41

Fructose 1,6BP to fructose 6P Enzyme = fructose 1,6 bisphosphatase

Question 42

What is the purpose of the Cori cycle?

Answer 42

Links the lactate produced from anaerobic glycolysis in RBC and exercising muscle to gluconeogenesis in the liver. Glucose in the liver is then transported back to RBCs and muscle

Question 43

The Cori cycle costs ____ ATP, prevents _________ accumulation, and regenerates ___________

Answer 43

4; lactate; glucose

Question 44

Von Gierke disease involves the inefficient release of free glucose into the bloodstream by the liver in gluconeogenesis and glycogenolysis. Patients exhibit marked fasting hypoglycemia, lactic acidosis, and hepatomegaly due to buildup of glycogen. Diet management is the primary therapeutic approach. What enzyme does this disease primarily affect?

Answer 44

Glucose 6-phosphatase

Question 45

Cleavage of sucrose by sucrase yields what 2 products?

Answer 45

Fructose | Glucose

Question 46

Cleavage of lactose by lactase yields what 2 products?

Answer 46

Galactose | Glucose

Question 47

Sperm require fructose as an energy source. What transporter do they utilize?

Answer 47

Fructose uptake requires GLUT5

Question 48

Galactose and glucose uptake occus via what transporter?

Answer 48

SGLT1

Question 49

A ________ deficiency results in elevated blood galactose. It classically presents as failure to thrive, liver failure, sepsis, and bleeding

Answer 49

GALT (glucose 1P uridyltransferase)

Question 50

A ___________ deficiency leads to the accumulation of galactitol in the lens of the eye and in neural tissue, resulting in galactosemia

Answer 50

Galactokinase

Question 51

The polyol pathway requires __________ ___________ to reduce glucose to sorbitol. Sorbitol dehydrogenase oxidizes sorbitol to ____________. Cells that lack this enzyme can accumulate sorbitol, which triggers water influx and swelling - manifesting as retinopathy, ____________, and peripheral neuropathy

Answer 51

Aldose reductase Fructose Cataracts

Question 52

Which is more efficiently converted to fat, glucose or fructose?

Answer 52

Fructose - can enter pathway later, bypassing key regulatory step in glycolysis

Question 53

Aldolase B deficiency is an inherited _______ intolerance, involving a deficient hepatic aldolase B that cleaves fructose 1P into G3P and DHAP. Often presents as liver damage, kidney disease, hypophosphatemia, hypoglycemia, and low tolerance for high-sugar foods

Answer 53

Fructose

Question 54

The PPP has an irreversible ______________ step, which is catabolic, and a reversible _______________ step, which is anabolic

Answer 54

Oxidative Non-oxidative

Question 55

What is the summary/yield of the oxidative phase of the PPP?

Answer 55

2 NADPH | 1 CO2

Question 56

What is the rate limiting step of the PPP and how is it regulated?

Answer 56

Glucose 6P --> 6 phosphogluconolactone Enzyme = G6PD Inhibited by NADPH

Question 57

________ deficiency affects a significant population, particularly those of African descent. Presentation of hemolytic anemia when NADPH need is elevated (infection, oxidizing medications, fava beans)

Answer 57

G6PD

Question 58

NADPH is responsible for regenerating ___________, an important antioxidant that detoxifies H2O2

Answer 58

Glutathione [glutathione reductase]

Question 59

Modulation of the PPP depends on cellular demand. When ribose 5P is in high demand, as is the case for rapidly dividing cells, the __________ phase is favored to produce ribulose 5P When NADPH is in high demand, ______________ products are channeled into gluconeogenesis for reentry into the PPP.

Answer 59

Oxidative Nonoxidative

Question 60

Which organs and tissues tend to exhibit high PPP activity?

Answer 60

Lungs, liver, phagocytic cells, lactating mammary glands, adipose tissue during FA synthesis

Question 61

Phagocytic cells require NADPH for what is called the respiratory burst, which produces O2 derived free radicals which lead to the formation of H2O2 and then ____________ (antibacterial agent)

Answer 61

Hypochlorite