Term
| When is glycogenesis the primary source of blood glucose? |
|
Definition
| From 3-4 hours after a meal to up to 18 hours p.c., when gluconeogenesis surpasses it as the primary source |
|
|
Term
| How much glycogen is stored in the liver during a fed state? |
|
Definition
|
|
Term
| Is glycogen stored anywhere besides the liver? |
|
Definition
| Yes, it is stored in muscle cells to be utilized for internal needs |
|
|
Term
|
Definition
| poly-α-D-glucose, attached at its reducing end to a glycogenin protein |
|
|
Term
| What sort of linkage creates a branch in glycogen? |
|
Definition
| An α1,6-linkage every 8-10 sugars |
|
|
Term
| How large can a glycogen molecule be? |
|
Definition
| It can be up to 400,000 monosaccharides, with 212 branches and several thousand non-reducing termini |
|
|
Term
| What is the advantage to having many non-reducing termini in a glycogen molecule? |
|
Definition
| A non-reducing end is where glucose is removed for energy, so with many branches breakdown can happen more rapidly |
|
|
Term
| Compare and contrast glycogen and starch |
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Definition
| Glycogen is more branched, but both are composed of many α1,4-linked glucose |
|
|
Term
| What enzyme converts glucose-1-phosphate to UDP-glucose? |
|
Definition
| UDP-glucose pyrophosphorylase |
|
|
Term
| Does it cost energy to convert glucose-1-phosphate to UDP-glucose? |
|
Definition
| Yes, the equivalent of two ATPs |
|
|
Term
| What protein does glycogenesis require at initial synthesis? How does this work? |
|
Definition
| Glycogenin, which autoglucosylates itself to form a primer for glycogen synthesis |
|
|
Term
| What enzyme elongates the glycogenin primer with many α1,4-linked glucose? |
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Definition
|
|
Term
| What enzyme adds branches during glycogenesis? How does it work? |
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Definition
| Branching enzyme Amylo-α1,4->α1,6-transglucosidase hydrolyzes 4-5 sugars from the end and transfers it to a glucose about 4 places downwards. Both new termini can be extended and branched again. |
|
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Term
| What enzyme breaks down glycogen by shortening a chain, and how does it work? |
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Definition
| Glycogen phosphorylase breaks a glycosidic bond and adds a PO4, saving energy and resulting in glucose-1-phosphate |
|
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Term
| Compare α-amylase to glycogen phosphorylase |
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Definition
| α-amylase doesn't add phosphate (so it will cost an ATP to generate glucose-1-P), and α-amylase is extracellular and less tightly controlled than intracellular glycogen phosphorylase |
|
|
Term
| Describe how the glucose-1-phosphate released from glycogenolysis becomes able to be transported extracellularly |
|
Definition
1. Phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate
2. Translocase transports it into the ER
3. glucose-6-phosphatase converts it to glucose, which can be transported extracellularly
Same technique as used in hepatic gluconeogenesis |
|
|
Term
| What is the alternate pathway (a few %) to breakdown glycogen? |
|
Definition
| Lysosomes break down glycogen using lysosomal α(1,4)-glucosidease (acid maltase) |
|
|
Term
|
Definition
| Glycogen storage disease type II: a deficiency in lysosomal α(1,4)-glucosidease (acid maltase) leads to vacuolar glycogen accumulation |
|
|
Term
| Define Andersen's disease |
|
Definition
| Glycogen storage disease type IV: It affect glycogen branching enzyme |
|
|
Term
|
Definition
Skeletal muscle glycogen phosphorylase deficiency
-Liver enzyme normal
-No rise in blood lactate during exercise
-Myoglobinemia and myoglobinuria
-Blood sugar normal
-Relatively benign |
|
|
Term
| Define Von Gierke Disease |
|
Definition
Glucose-6-phosphate Translocase Deficiency
-Affects liver and kidney
-Severe fasting hypoglycemia
-Hepato and reno megaly
-Growth retardation
-High urea, lactic, lipids in blood
-So severe because the translocase is also in gluconeogenesis |
|
|
Term
| Describe the pathway by which glucagon/epinephrine would affect glycogenolysis |
|
Definition
1. Glucagon/epinephrine activates adenylyl cyclase
2. cAMP activates protein kinase A
3. Protin kinase A phosphorylates Glycogen
phyosphorylase kinase to its active a form
4. Glycogen phosphorylase kinase a activates glycogen phosphorylase
5. Glycogen phosphorylase breaks down glycogen |
|
|
Term
| List some activators of Glycogen phosphorylase |
|
Definition
Calcium, AMP, and protein kinase A (directly)
Glucagon/epinephrine (indirectly) |
|
|
Term
| How does calcium activate glycogen phosphorylase? |
|
Definition
During muscle activity, Ca2+ is released
It then binds to the calmodulin subunit of Glycogen phosphorylase kinase, activating it without phosphorylation
Glycogen phosphorylase kinase then activates glycogen phosphorylase |
|
|
Term
| How does AMP activate glycogen phosphorylase? |
|
Definition
AMP binds to Glycogen phosphorylase kinase, activating it without phosphorylation
Glycogen phosphorylase kinase then activates glycogen phosphorylase |
|
|
Term
| How does insulin inactivate glycogen phosphorylase? |
|
Definition
| Insulin activates protein phosphatase-1, which dephosphorylates and returns glycogen phosphorylase kinase and glycogen phosphorylase to their less active b-forms |
|
|
Term
| How does glucagon affect glycogen synthase? |
|
Definition
| Glucagon activates cAMP-dependent protein kinase A, which phosphorylates glycogen synthase, converting it to its b-form |
|
|
Term
| How does insulin affect glycogen synthase? |
|
Definition
| Insulin activates protein-phosphatase 1, which dephosphorylates glycogen synthase, converting it to its a-form |
|
|
Term
| What is the effect of insulin-activated protein phosphatase 1 on glycogen? |
|
Definition
| Protein phosphatase 1 converts glycogen synthase to its a form and glycogen phosphorylase to its b form |
|
|
Term
| List some inhibitors of glycogen phosphorylase |
|
Definition
Glucose/Glucose-6-P, ATP, and protein phosphatase 1 directly
Insulin indirectly |
|
|
Term
| Describe how galactose compares to glucose |
|
Definition
| Galactose is a 4-epimer of glucose |
|
|
Term
| Describe how mannose is related to glucose |
|
Definition
| Mannose is a 2-epimer of glucose |
|
|
Term
| Where is fructose found in the diet? |
|
Definition
| 55g/day on average, it occurs primarily with glucose as the diassarcharide sucrose and in fruits |
|
|
Term
| Where is galactose found? |
|
Definition
| With glucose as the milk disaccharide lactose, and is also a component of glycoproteins and glycolipids |
|
|
Term
| How does fructose, galactose, and mannose get into cells? |
|
Definition
| Transport catalyzed by GLUTs, insulin-independent |
|
|
Term
| How does fructose, galactose, and mannose affect insulin? |
|
Definition
| These sugars do not promote secretion of insulin |
|
|
Term
| Describe how fructose enters glycolysis |
|
Definition
1. Fructose is phosphorylated by fructokinase
2. Fluctose 1-phosphate is cleaved by aldolase B into dihydroxyacetone phosphate and glyceraldehyde (bypassing control via phosphofructokinase) |
|
|
Term
| What is one theory suggesting why fructose corn syrup might be more fattening than traditional sugar? |
|
Definition
| When fructose-1-phosphate is cleaved by aldolase B, this step bypasses traditional glycolytic control via phosphofructokinase-1 |
|
|
Term
| Where is fructose utilization greatest? |
|
Definition
| Liver mainly and also kidneys, because those are where fructokinase and aldolase B are most abundant |
|
|
Term
| When fructose-1-phosphate is split by aldolase B, what happens to the glyceraldehyde? |
|
Definition
| It can be phosphorylated by triose kinase to enter glycolysis, or reduced and phosphorylated to glycerol phosphate (a lipid precursor) |
|
|
Term
| Describe essential fructosuria disease |
|
Definition
| Lack of fructokinase, benign condition where fructose is wasted in the urine |
|
|
Term
| Define Heriditary fructose intolerance |
|
Definition
Absence of aldolase B
Fructose-1-phosphate accumulates, wasting ATP and causing severe osmotic problems and hepatic failure |
|
|
Term
|
Definition
| A polyol derived by reduction (aldolase reductase) of the aldehyde of glucose to an alcohol, a process which traps it in the cytoplasm |
|
|
Term
| What area of the body is especially dependent on sorbitol? |
|
Definition
| The seminal vesicles, as it is then converted into fructose for sperm nutrient |
|
|
Term
| What enzyme converts glucose to sorbitol? |
|
Definition
|
|
Term
| What enzyme converts sorbitol to fructose? |
|
Definition
|
|
Term
| When and where does excess sorbitol become a problem? |
|
Definition
Excess sorbitol can occur under conditions of high intracellular glucose (eg diabetes)
This can cause deleterious osmotic swelling in lens, nerves, kidneys |
|
|
Term
| How is mannose incorporated into glycolysis? |
|
Definition
Mannose is trapped intracellularly and phosphorylized into mannose-6-phosphate.
It is then isomerized into fructose-6-phosphate to enter mainstream metabolism |
|
|
Term
| What enzyme converts mannose-6-phosphate into fructose-6-phosphate? |
|
Definition
|
|
Term
| How is galactose trapped intracellularly? |
|
Definition
| It is phosphorylaed to galactose 1-phosphate by galactokinase |
|
|
Term
| What enzyme converts galactose-1-phosphate and UDP glucose to UDP-galactose and glucose-1-phosphate? |
|
Definition
| galactose-1-phosphate uridyltransferase |
|
|
Term
| What happens to the glucose-1-phosphate generated from galactose-1-phosphate and UDP-glucose? |
|
Definition
| Phosphoglucomutase converts it to glucose-6-phosphate to enter mainstream metabolism |
|
|
Term
| How is UDP-galactose important in a cell? |
|
Definition
| It is a precursor for synthesis of lactose, glycolipids, glycoproteins, and glycosaminoglycans |
|
|
Term
| What enzyme converts UDP-Galactose to UDP-glucose? |
|
Definition
|
|
Term
| Describe Galactokinase deficiency |
|
Definition
| Disorder that leads to elevated galactose in blood; can cause accumulation of galacitol by aldose reductase, causing cataracts |
|
|
Term
| Describe Classic galactosemia |
|
Definition
Galactose-1-phosphate uridyltransferase deficiency, leading to accumulation of galactose-1-phosphate and galacitol
Similar metabolic and osmotic problems as hereditary fructose intolerance |
|
|
Term
| What is another name for the pentose phosphate pathway |
|
Definition
| Hexose monophosphate shunt |
|
|
Term
| Define the pentose phosphate pathway and list what the net products are |
|
Definition
| An alternative pathway of glucose oxidation, where ribose phosphate and NADPH is formed but ATP is not |
|
|
Term
| What happens to the NADPH formed by the pentose phosphate pathway? |
|
Definition
| They become available to enzymes involved in anabolic reactions, and for reduction of reactive oxygen species and exogenous agents |
|
|
Term
| Where is the pentose phosphate pathway more active? |
|
Definition
Tissues where there is a high need for NADPH for anabolic reactions or redox regulation
examples: liver, lactating mammary gland, adipose tissue, testis, ovaries, placenta, adrenal cortex, erythrocytes |
|
|
Term
| How does NADPH compare to NADH? |
|
Definition
They are identical except that NADPH has a phosphate group
NADH typically donates its electrons to the electron transport chain, whereas NADPH is typically used for anabolic reactions and ROS oxidation |
|
|
Term
What is the steady state ratio of NADP+:NADPH?
What is the ratio for NAD+:NADH? |
|
Definition
NADP+:NADPH = ~1:10
NAD+:NADH = ~1000:1 |
|
|
Term
| What are the two phases of the pentose phosphate pathway? Briefly describe them. |
|
Definition
Oxidative: irreversible conversion of 6 hexoses to 6 pentoses and CO2
Nonoxidative: reversible translocation of carbon chains to yield glycolytic intermediates |
|
|
Term
| How does glucose-6-phosphate get converted to ribulose-5-phosphate? |
|
Definition
It is oxidized with an intermediate of 6-phosphogluconate
(not certain if need to know, but self-descriptive anyway)
Enzymes used: glucose-6-phosphate dehydrogenase, 6-phosphogluconolacetone hydrolase, 6-phosphogluconate dehydrogenase |
|
|
Term
| What is the important enzyme that begins the pentose phosphate pathway from glucose-6-phosphate? |
|
Definition
| Glucose-6-phosphate dehydrogenase |
|
|
Term
| How is the oxidative phase of the pentose phosphate pathway regulated? |
|
Definition
It is regulated by a demand for NADPH, a strong competitive inhibitor of glucose-6-phosphate dehydrogenase
Therefore, if low NADPH, glucose-6-phosphate dehydrogenase will lead to production of pentose phosphates |
|
|
Term
| Is glucose-6-phosphate the only sugar that can enter the pentose phosphate pathway? |
|
Definition
No, other glycolytic intermediates (fructose-6-phosphate, glyceraldehyde-3-phosphate) can enter on the nonoxidative side, but they skip the NADPH formation step
This would happen if ribose was needed and there were substrate supply |
|
|
Term
| How do the nonoxidative reactions in the pentose phosphate pathway basically work? |
|
Definition
Glycolytic intermediates are catalyzed by transketolases and transaldolases to essentially move their carbons around to either get to ribose-6-phosphate or another intermediate
The carbon numbers in both chains will add up to 10 |
|
|
Term
| List three dangerous hydroxyl radicals |
|
Definition
| Superoxide, hydrogen peroxide, hydroxyl radical |
|
|
Term
| Why is NADPH needed for reactive oxygen species? |
|
Definition
| NADPH is often the ultimate source of electrons to oxidize and get rid of the reactive oxygen species |
|
|
Term
| What enzyme converts hydrogen peroxide to oxygen and water? |
|
Definition
|
|
Term
| What enzyme converts superoxide (O •2- to oxygen and hydrogen peroxide? |
|
Definition
|
|
Term
|
Definition
| A tripeptide that can reduce H2O2 in a reaction catalyzed by glutathione peroxidase |
|
|
Term
| What enzyme converts 2 GSH and hydrogen peroxide to water and GSSG? |
|
Definition
|
|
Term
| What happens to GSSG after the 2 G-SH have transformed hydrogen peroxide? |
|
Definition
| It is reduced and restored by oxidation of NADPH catalyzed by glutathione reductase |
|
|
Term
| What is the purpose of NADPH oxidase? |
|
Definition
| To transfer electrons from NADPH to O2 to generate a superoxide bactericidal respiratory burst in phagosomes |
|
|
Term
| What enzyme is responsible for catalyzing the bactericidal respiratory burst? |
|
Definition
|
|
Term
| Describe NADPH oxidase deficiency |
|
Definition
This will lead to phagocytes not being able to do the respiratory burst
Chronic disease, infections, and formation of granulomas (nodular areas of inflammation to sequester bacteria) |
|
|
Term
| What cells are especially dependent on the pentose phosphate pathway, and why? |
|
Definition
| Erthrocytes, because they do not have fatty acid biosynthesis pathways |
|
|
Term
| Describe Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) |
|
Definition
The most common human enzyme abnormality disease
Under stress, erthrocytes cannot undergo the pentose phosphate pathway, causing increased free radicals |
|
|
Term
|
Definition
| Formations in erythrocytes of hemoglobin sylfhydryl groups to protect them from free radicals under G6PD deficiency |
|
|
Term
| What are some stressors that can lead to symptoms of G6PD deficiency? |
|
Definition
| Oxidant drugs (antibiotics, antipyretics and antimalarials), favism (fava bean ingestion), and infection (radicals formed in inflammatory macrophages) |
|
|
Term
| Does G6PD deficiency become worse as the red blood cell ages? |
|
Definition
| No, G6PD naturally is used less as the cell ages, since ribosomes are no longer needed for replacement |
|
|
Term
| Why is G6PD the most common enzyme deficiency? |
|
Definition
| Plasmodium (malaria agents) are highly succeptible to oxidative damage, giving individuals whose red blood cells lack G6PD an advantage |
|
|
Term
| What enzyme can produce NADPH from fatty acid biosynthesis pathways? |
|
Definition
NADP+ dependent malate dehydrogenase
Absent in erythrocytes |
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|
