Glucose Metabolism Flashcards
What cell type depends exclusively on glycolysis to generate ATP?
Erythrocytes (RBCs)
Glucose is the major monosaccharide utilized in glycolysis, but _________ and ___________ can also be used
Fructose; galactose
Glucose is polar, so it cannot cross the plasma membrane. How is it transported into the cell?
It is phosphorylated (becomes glucose 6-phosphate) by hexokinase or glucokinase, thus trapping it in the cell
Which glucose transporter is the main transporter in the brain?
GLUT3
Which glucose transporter is insulin-dependent, and is found in skeletal muscle, heart, and adipose tissue?
GLUT4
Which glucose transporter facilitates the unregulated uptake (independent of insulin) and is localized to the liver?
GLUT2
Describe the affinity of GLUT2 for glucose
GLUT2 is localized to the liver, so it has low affinity
What pathological condition is related to the GLUT2 receptor in the liver?
Fanconi-Bickel syndrome
Which glucose transporter facilitates unregulated glucose transfer, especially in RBCs and the brain. This transporter has high affinity and is saturated at all times
GLUT1
Of the 4 glucose transporters, which ones are regulated by insulin?
GLUT2 and GLUT4
How does insulin signaling regulate the GLUT4 transporter?
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
What is the net production of glycolysis?
2 pyruvate
2 ATP
2 NADH
What are the 2 potential fates of pyruvate in aerobic fed conditions?
Converted to Acetyl CoA via PDH and enters TCA, fatty acid synthesis
Converted to Alanine via alanine aminotransferase and begins protein synthesis
What is the fate of pyruvate in aerobic fasting conditions?
Converted to oxaloacetate via pyruvate carboxylase and enters gluconeogenesis
What are the 2 potential fates of pyruvate in anaerobic conditions?
Converted to lactate via lactate dehydrogenase and enters the Cori cycle
Converted to Alanine via alanine aminotransferase and enters gluconeogenesis or urea cycle
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 _______.
Cytoplasm 3 2 DHAP 4 2
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?
Hexokinase - found in all tissues, high affinity for glucose
Glucokinase - found in the liver and pancreatic beta cells, low affinity for glucose
What is the rate limiting step of glycolysis?
Phosphorylation of G6P to fructose 1,6BP
Enzyme = phosphofructokinase-1 (PFK1)
What intermediate in glycolysis can get shunted to the PPP? What other pathway can it be shunted to?
G6P
Glycogen synthesis/breakdown
Describe the “splitting” phase of glycolysis
Cleavage of 6-carbon Fructose 1, 6-BP to produce 3-carbon DHAP and 3-carbon G3P
Enzyme = aldolase
Describe the isomerization step of glycolysis
After F1,6BP is split into DHAP and G3P, the two isomeric products interconvert via triose phosphate isomerase
What are the 3 irreversible steps of glycolysis?
Glucose –> Glucose 6P
Fructose 6-P –> Fructose 1,6BP (RL)
Phosphonolpyruvate –> pyruvate
What enzyme catalyzes the formation of pyruvate from phosphoenolpyruvate in glycolysis?
Pyruvate kinase
What effect would AMP or F2,6BP have on PFK in glycolysis?
Activation
What effect would ATP and citrate from the TCA cycle have on PFK in glycolysis?
Inhibition
In glycolysis, what hormonal conditions activate protein phosphatases, dephosphorylate PFK-2/FBPase-2 (triggers kinase activity), and produces F2,6BP which activates PFK1?
High insulin/low glucagon
In glycolysis, what hormonal conditions induce high [cAMP], activate protein kinase A, phosphorylate PFK-2/FBPase2 (triggers phosphorylation activity), and reduce PFK1 activity?
High glucagon/low insulin
What effect would F1,6BP have on pyruvate kinase?
Activation
What are the 2 inhibitors of pyruvate kinase?
ATP and Ala
- PEP will begin gluconeogenesis
What is the most common clinical presentation of someone with defective glycolytic enzymes like phosphoglucose isomerase, aldolase A, triose phosphate isomerase, and pyruvate kinase?
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
The majority of diseases caused by defects in glycolytic enzymes are associated with which enzyme specifically?
Pyruvate kinase
What condition could elevate Phe in fetal brains and effectively disrupt glycolysis by inhibiting PK?
PKU
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?
Tarui disease
_________ is compensated for by anaerobic glycolysis, which leads to a buildup of lactate and causes lactic acidosis?
Hypoxia
Differentiate between type 1 and type 2 diabetes
Type 1: insulin deficiency
Type 2: insulin resistance
Where does gluconeogenesis occur?
Primarily in the liver, but also in kidneys and small intestine
Cytosol and mitochondria
The irreversible steps of glycolysis require “bypass” steps in gluconeogenesis. What are the key bypass enzymes corresponding to the following step?:
Pyruvate kinase
PEP carboxylase and pyruvate carboxylase
The irreversible steps of glycolysis require “bypass” steps in gluconeogenesis. What are the key bypass enzymes corresponding to the following step?:
PFK-1
Fructose 1,6 Bisphosphatase
The irreversible steps of glycolysis require “bypass” steps in gluconeogenesis. What are the key bypass enzymes corresponding to the following step?:
Hexokinase/glucokinase
Glucose 6-phosphatase
What is the purpose of the malate shuttle
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
What is the rate limiting step of gluconeogenesis?
Fructose 1,6BP to fructose 6P
Enzyme = fructose 1,6 bisphosphatase
What is the purpose of the Cori cycle?
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
The Cori cycle costs ____ ATP, prevents _________ accumulation, and regenerates ___________
4; lactate; glucose
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?
Glucose 6-phosphatase
Cleavage of sucrose by sucrase yields what 2 products?
Fructose
Glucose
Cleavage of lactose by lactase yields what 2 products?
Galactose
Glucose
Sperm require fructose as an energy source. What transporter do they utilize?
Fructose uptake requires GLUT5
Galactose and glucose uptake occus via what transporter?
SGLT1
A ________ deficiency results in elevated blood galactose. It classically presents as failure to thrive, liver failure, sepsis, and bleeding
GALT (glucose 1P uridyltransferase)
A ___________ deficiency leads to the accumulation of galactitol in the lens of the eye and in neural tissue, resulting in galactosemia
Galactokinase
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
Aldose reductase
Fructose
Cataracts
Which is more efficiently converted to fat, glucose or fructose?
Fructose - can enter pathway later, bypassing key regulatory step in glycolysis
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
Fructose
The PPP has an irreversible ______________ step, which is catabolic, and a reversible _______________ step, which is anabolic
Oxidative
Non-oxidative
What is the summary/yield of the oxidative phase of the PPP?
2 NADPH
1 CO2
What is the rate limiting step of the PPP and how is it regulated?
Glucose 6P –> 6 phosphogluconolactone
Enzyme = G6PD
Inhibited by NADPH
________ deficiency affects a significant population, particularly those of African descent. Presentation of hemolytic anemia when NADPH need is elevated (infection, oxidizing medications, fava beans)
G6PD
NADPH is responsible for regenerating ___________, an important antioxidant that detoxifies H2O2
Glutathione
[glutathione reductase]
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.
Oxidative
Nonoxidative
Which organs and tissues tend to exhibit high PPP activity?
Lungs, liver, phagocytic cells, lactating mammary glands, adipose tissue during FA synthesis
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)
Hypochlorite
