Carbohydrate metabolism (midterm) Flashcards

Question

In what direction do GLUT transporters move glucose?

Answer 1

Either direction, depending on the concentration gradient In intestinal mucosae, the transport is generally from the lumen to the cytosol

Answer 2

* RBCs * Blood–brain barrier * Blood–retinal barrier * Blood–placental barrier * Blood–testis barrier

Answer 3

* High affinity, low efficiency * Low K_m * Low V_max

Answer 4

* Liver * Kidney * Pancreatic β-cells * Serosal surface of intestinal mucosal cells

Answer 5

* Low affinity * High efficiency

Answer 6

* Neurons of the brain

Answer 7

* Major transporter in the CNS * High affinity

Answer 8

* Adipose tissue * Skeletal muscle * Heart muscle

Answer 9

* High efficiency * Sensitive to insulin: ↑insulin leads to increase in number of GLUT 4 transporters on the cell surface

Answer 10

* Intestinal epithelium * Spermatozoa

Answer 11

* Glucose * Fructose * Galactose

Answer 12

* GLUT 2: Glc, Frc, Gal * GLUT 5: Frc only

Answer 13

Glucogenic tissues (tissues where gluconeogenesis occurs)—in the ER membrane

Answer 14

* Facilitated (saturable) diffusion of glucose * They alter between two conformational states (open to the cytosol or open to the outside)

Answer 15

* Proximal convoluted tubules of nephrons * Small intestine mucosa

Answer 16

Secondary active transport (cotransport) of glucose using the concentration gradient of Na⁺

Answer 17

* Two catalytic subunits * Two regulatory subunits

Answer 18

* cAMP molecules bind to the 2 binding sites on each regulatory subunit * The two catalytic subunits are activated and released (separately)

Answer 19

* 2 ATP * 2 NADH * 2 pyruvate

Answer 20

glucose + ATP → glucose-6-phosphate + ADP Catalyzed by hexokinase or glucokinase

Answer 21

* Step 1 (glucose phosphorylation) * Step 3 (fructose-6P phosphorylation) * Step 10 (pyruvate formation)

Answer 22

* Hexokinase: found in most tissues. Low K_m, low V_max. Allosterically regulated * Glucokinase: found in hepatocytes and pancreatic β cells. Higher K_m, very high V_max. Hormonally regulated

Answer 23

* Found in most tissues * Broad substrate specificity: it can phosphorylate other hexoses * Low K_m, allowing for some activity at low [glucose] * Low V_max, so it cannot trap more glucose than the cell needs * Affected by feedback inhibition

Answer 24

* Found in hepatocytes and pancreatic β cells * Specific to glucose * Higher K_m: it only functions at > 100 mg dL^–1 * Very high V_max, so it sequesters glucose in the cell * Activity induced by presence of glucose or insulin

Answer 25

glucose-6-phosphate ⇌ fructose-6-phosphate Catalyzed by phosphoglucose isomerase

Answer 26

fructose-6-phosphate + ATP → fructose-1,6-bisphosphate + ADP Catalyzed by phosphofructokinase-1

Answer 27

Step 3 (fructose-6P phosphorylation)

Answer 28

Step 3 (fructose-6P phosphorylation)

Answer 29

glucose-6-phosphate ⇌ glyceraldehyde-3-phosphate + dihydroxyacetone phosphate Catalyzed by aldolase

Answer 30

dihydroxyacetone phosphate ⇌ glyceraldehyde-3-phosphate Catalyzed by triose phosphate isomerase

Answer 31

GAP is consumed by the later steps of glycolysis, pulling the equilibrium in favor of its production

Answer 32

glyceraldehyde-3-phosphate + P_i + NAD⁺ + 2H⁺ ⇌ 1,3-bisphosphoglycerate + NADH + H⁺ Catalyzed by glyceraldehyde-3-phosphate dehydrogenase

Answer 33

The oxidation of glyceraldehyde to glycerate releases enough energy for the addition of a phosphate

Answer 34

* Used for cellular metabolism (including the glycerol-3-phosphate shuttle) * "Transported" to the mitochondria via the malate–aspartate shuttle

Answer 35

1,3-bisphosphoglycerate + ADP + P_i ⇌ 3-phosphoglycerate + ATP Catalyzed by phosphoglycerate kinase

Answer 36

3-phosphoglycerate ⇌ 2-phosphoglycerate Catalyzed by phosphoglycerate mutase

Answer 37

2-phosphoglycerate ⇌ H₂O + phosphoenolpyruvate Catalyzed by enolase

Answer 38

phosphoenolpyruvate + ADP + P_i → pyruvate + ATP Catalyzed by pyruvate kinase

Answer 39

Instead of step 7 (first ATP production): * Bisphosphoglycerate mutase isomerizes 1,3-BPG to **2**,3-BPG * A phosphatase converts 2,3-BPG to 3-phosphoglycerate, releasing pyruvate using water * 3-PG re-enters glycolysis at step 8

Answer 40

* 2,3-BPG binds to deoxy-hemoglobin more strongly than O₂, preventing O₂ from rebinding * In the systemic circulation, this promotes oxygen delivery by preventing it from rebinding to hemoglobin

Answer 41

* pyruvate → acetaldehyde + CO₂, using TPP as a coenzyme * acetaldehyde + NADH → ethanol + NAD⁺ The entire reaction is catalyzed by pyruvate decarboxylase

Answer 42

pyruvate + NADH ⇌ lactate + NAD⁺ Catalyzed by lactate dehydrogenase

Answer 43

* In exercising skeletal muscle, as NADH is formed by catabolism and there is not enough NAD⁺ for glycolysis * As a coping mechanism for brief periods of hypoxia * In cells with low energy demands

Answer 44

* Decreased lactate utilization * Increased lactate production * Collapse of the circulatory system, leading to impaired O₂ transport (as in respiratory failure, uncontrolled hemorrhage, myocardial infarction) * Decreased pyruvate utilization (shifting equilibrium to lactate formation), as in lowered gluconeogenesis (pyruvate carboxylase) or TCA (pyruvate dehydrogenase) activity * Alcohol intoxication: buildup of NADH; lactate dehydrogenase is used to regenerate NAD⁺

Answer 45

* Hexokinase/glucokinase * Phosphofructokinase-1 * Pyruvate kinase

Answer 46

**Activators** * AMP * Fructose-2,6-bisphosphate * Insulin **Inhibitors** * ATP * citrate * H⁺ * Glucagon

Answer 47

**Activators** * Fructose-1,6-bisphosphate (feedforward activation) * Insulin **Inhibitors** * ATP * Alanine * Glucagon (by phosphorylating the enzyme via protein kinase A)

Answer 48

**Inhibitors** * Glucose-6-phosphate (feedback inhibition)

Answer 49

Glucokinase can be sequestered (inactivated) in the nucleus by binding to glucokinase regulatory protein (GKRP) GK_cyt ⇌ GK–GKRP_nuc * Glucose activates the reverse reaction (liberation/activation) * Fructose-6-phosphate activates the forward reaction (sequestration/inactivation)

Answer 50

* Increasing [ATP] past a certain point usually causes steep, immediate inhibition of PFK-1 * AMP and F-2,6-BP slow down the inhibiting effect of ATP

Answer 51

* High insulin:glucagon reduces [cAMP] and inactivates protein kinase A * Reduced protein kinase A activity favores dephosphorylation of the bifunctional enzyme PFK-2 * Dephosphorylated PFK-2 functions as a kinase, producing fructose-2,6-bisphosphate * F-2,6-BP is an activator of PFK-1

Answer 52

* Low insulin:glucagon increases [cAMP] and activates protein kinase A * Activated protein kinase A phosphorylates the bifunctional enzyme PFK-2 * Phosphorylated PFK-2 functions as a phosphatase, degrading fructose-2,6-bisphosphate * F-2,6-BP is an activator of PFK-1, so its decreased concentration removes the activation of PFK-1

Answer 53

* Brain * RBCs * Kidney medulla * Lens of the eye * Cornea of the eye * Testes * Exercising muscle

Answer 54

* Glycogenolysis in the liver * Gluconeogenesis in the liver and kidneys

Answer 55

* Liver (90% in an overnight fast, 60% in prolonged fasting) * Kidneys (10% in an overnight fast, 40% in prolonged fasting)

Answer 56

The synthesis of glucose from **non-carbohydrate** sources

Answer 57

* **As pyruvate**: some glucogenic amino acids; lactate * **As oxaloacetate**: some glucogenic amino acids; propionate (propanoate) * **As triose phosphates**: glycerol (from triacylglycerols or otherwise)

Answer 58

* They are converted to α-ketoacids, e.g. α-ketoglutarate * The α-ketoacids enter the Krebs cycle and form oxaloacetate * Oxaloacetate is an intermediate of gluconeogenesis

Answer 59

* Glycerol is phosphorylated by *glycerol kinase* to glycerol-3-phosphate * Glycerol-3-phosphate is oxidized by *glycerol-3P dehydrogenase* to dihydroxyacetone phosphate, an intermediate of glycolysis and gluconeogenesis

Answer 60

* Gluconeogenesis * Glycogenesis

Answer 61

* Glycolysis * Glycogenolysis

Answer 62

Four (steps 1, 2, 9, and 11)

Answer 63

2 GTP + 4 ATP (⇒ 6 NTP total)

Answer 64

Glycolysis has three irreversible steps which must be reversed via other mechanisms

Answer 65

pyruvate + CO₂ + ATP → oxaloacetate + ADP + P_i Catalyzed by pyruvate carboxylase; biotin as a coenzyme

Answer 66

Activating the CO₂ and binding it to biotin. No phosphorylation takes place

Answer 67

oxaloacetate + GTP → phosphoenolpyruvate + CO₂ + GDP Catalyzed by PEP-carboxykinase

Answer 68

* In the mitochondrion, oxaloacetate is reduced to malate by *malate dehydrogenase_mit* * Malate can be transported to the cytosol by a specific translocase * In the cytosol, malate is oxidized back to oxaloacetate by *malate dehydrogenase_cyt* oxaloacetate + NADH ⇌ malate + NAD⁺

Answer 69

Covalently bound to the ε-amino group of a Lys residue in the enzyme

Answer 70

fructose-1,6-bisphosphate + H₂O → fructose-6-phosphate + P_i Catalyzed by fructose-1,6-bisphosphatase

Answer 71

glucose-6-phosphate + H₂O → glucose + P_i Catalyzed by glucose-6-phosphatase

Answer 72

* Glucose-6-phosphate translocase transports G-6P into the ER * GLUT-7 transports glucose out of the ER

Answer 73

* Pyruvate carboxylase * Fructose-1,6-bisphosphatase

Answer 74

**Allosteric activators** * Elevated acetyl CoA levels **Allosteric inhibitors** * Low acetyl CoA levels

Answer 75

**Inhibitors** * Fructose-2,6-bisphosphate **Activators** * Glucagon (by affecting formation of F-2,6-BP)

Answer 76

* Low insulin:glucagon increases [cAMP] and activates protein kinase A * Activated protein kinase A phosphorylates the bifunctional enzyme PFK-2 * Phosphorylated PFK-2 functions as a phosphatase, degrading fructose-2,6-bisphosphate * F-2,6-BP is an inhibitor of F-1,6-bisphosphatase, so its decreased concentration removes the activation of F-1,6-bisphosphatase

Answer 77

* Decreasing inhibition of fructose-1,6-bisphosphatase * Inhibition of pyruvate kinase, which slows glycolysis, allowing gluconeogenesis to predominate * Induction of the synthesis of the gene for PEP-carboxykinase

Answer 78

Glycogenolysis is more rapid than gluconeogenesis

Answer 79

* A homopolysaccharide of glucose * Each chain is formed of α(1→4) glycosidic bonds * Every 8–10 glucosyl residues, there is a branch, formed by a single α(1→6) glycosidic bond * A single glycogen molecule can contain hundreds of thousands of glucosyl residues, up to 10⁸ Da

Answer 80

* 400 g in resting skeletal muscle (1–2% of fresh weight) * 100 g in the well-fed adult liver (10% of fresh weight)

Answer 81

* Liver glycogen: depleted during a fast * Skeletal muscle glycogen: not affected by short fasts (a few days), moderately decreased in prolonged fasts (weeks)

Answer 82

* Glucose-1-phosphate from breaking α(1→4) bonds * Free glucose from breaking each α(1→6) bond

Answer 83

* *Glycogen phosphorylase* removes a glucosyl residue from the nonreducing ends by simple phosphorolysis (in the absence of ATP), breaking a α(1→4) glycosidic bond * The glucose residue is liberated as glucose-1-phosphate * This continues until there are 4 glucosyl units **before** the branching point—this is the **limit dextrin**

Answer 84

Four glucosyl residues (with a nonreducing end) **before** a branching point

Answer 85

* The branch is shortened to 4 residues, **including** the one attached to the main chain * A bifunctional debranching enzyme removes the outer 3 residues (breaking an α(1→4) bond) and attaches them to the nonreducing end of the main chain (forming an α(1→4) bond). This is **4:4 transferase** activity * The same bifunctional debranching enzyme breaks the remaining α(1→6) bond, liberating the last residue of the branch as free glucose. This is **α(1→6)-glucosidase** activity

Answer 86

* 4:4 transferase: the enzyme moves the 3 outer residues of a branch to the main chain, breaking and reforming an α(1→4) bond * α(1→6)-glucosidase: the enzyme breaks the α(1→6) bond joining the last branch residue to the branching point of the main chain, releasing free glucose

Answer 87

glucose-1-phosphate → glucose-6-phosphate Catalyzed by phosphoglucomutase, in the cytosol

Answer 88

**Liver** * Glucose-6-phosphate is transported into the ER by glucose-6P translocase, where it is dephosphorylated by glucose-6-phosphatase * Free glucose is released from the ER by GLUT 7 **Skeletal muscle** * Lacks glucose-6-phosphatase, so free glucose is never produced. Instead G-6P can enter glycolysis * This is why skeletal muscle cannot release glucose into the blood

Answer 89

* α-ᴅ-glucose attached to UDP * A glycogen fragment or the protein glycogenin

Answer 90

glucose-1-phosphate + UTP ⇌ UDP–glucose + PP_i Catalyzed by UDP-glucose pyrophosphorylase ## Footnote The PP_i is released from UTP. The phosphate group in glucose-1P is preserved

Answer 91

PP_i → 2P_i * Catalyzed by pyrophosphatase * This is necessary to keep the equilibrium of the UDP-glucose phosphorylase reaction in favor of UDP-glucose formation

Answer 92

Glycogen synthase

Answer 93

* A glycogen fragment * Glycogenin, in the absence of a glycogen fragment

Answer 94

* The –OH of a Tyr residue accepts a glucose residue from UDP-glucose (catalyzed by glycogenin itself via autoglucosylation) * Glycogenin catalyzes the transfer of the next few molecules of glucose from UDP-glucose, until a short chain is formed

Answer 95

UDP-glucose + glycogen_(n) ⇌ glycogen_(n+1) + UDP Catalyzed by glycogen synthase, forming an α(1→4) bond

Answer 96

* A branching enzyme removes 6–8 glucosyl residues from the nonreducing end of the main glycogen branch, breaking an α(1→4) bond * The branching enzyme adds the 6–8 residues to a non-terminal glucosyl residue, creating an α(1→6) bond * This is **4:6 transferase** activity * Both of the nonreducing ends formed are elongated by glycogen synthase

Answer 97

* Genetic diseases * Cause a defect or deficiency in an enzyme required for glycogen synthesis or degradation * Cause accumulation of excessive amounts of normal glycogen (if degradation is affected) or abnormal glycogen (if synthesis is affected) * Can affect one or more tissue * Range in severity from fatal in infancy to mild disorder throughout life

Answer 98

* Type Ia: von Gierke disease (glucose-6-phosphatase deficiency) * Type Ib: glucose-6-phosphate translocase deficiency * Tye II: Pompe disease (lysosomal α(1→4)-glucosidase deficiency) * Type V: McArdle syndrome (muscle glycogen phosphorylase deficiency)

Answer 99

Type II (Pompe disease)

Answer 100

1–3% is degraded in lysosomes by lysosomal α(1→4)-glucosidase (acid maltase)

Answer 101

Deficiency in glucose-6-phosphatase prevents liberation of free glucose in the liver, kidneys, and intestines

Answer 102

Deficiency in glucose-6-phosphate translocase prevents liberation of free glucose in the liver, kidneys, and intestines

Answer 103

* Affect the liver, kidneys, and intestine * Cause severe fasting hypoglycemia * Fatty liver, hepatomegaly, renomegaly * Progressive renal disease * Growth retardation and delayed puberty * Normal glycogen structure, but excess glycogen storage

Answer 104

Deficiency of glycogen phosphorylase in skeletal muscle

Answer 105

* Only skeletal muscle cells are affected * Weakness and cramping of the muscle after exercise * No increase in lactate levels during exercise

Answer 106

Deficiency in lysosomal α(1→4)-glucosidase

Answer 107

* Affects liver, muscle, and heart * Excessive glycogen found in **abnormal** vacuoles in the lysosomes * Normal blood sugar levels * Normal glycogen structure * Massive cardiomegaly * Early death from heart failure

Answer 108

**Activators** * Glucagon * Epinephrine **Inhibitors** * Insulin

Answer 109

* Glucagon/epinephrine activate G_αs, increasing [cAMP] * cAMP activates protein kinase A * Protein kinase A phosphorylates glycogen phosphorylase to **glycogen phosphorylase a** * Glycogen phosphorylase a is active, so glycogen is degraded

Answer 110

* Insulin activates phosphodiesterase, decreasing [cAMP], so protein kinase A is gradually inactivated * Insulin activates protein phosphatase 1, which dephosphorylates glycogen phosphorylase to **glycogen phosphorylase b** * Glycogen phosphorylase b is inactive, so glycogen is not degraded

Answer 111

**Activators** * Insulin **Inhibitors** * Glucagon * Epinephrine

Answer 112

* Glucagon/epinephrine activate G_αs, increasing [cAMP] * cAMP activates protein kinase A * Protein kinase A phosphorylates glycogen synthase to **glycogen synthase b** * Glycogen synthase b is inactive, so glycogen is not synthesized

Answer 113

* Insulin activates phosphodiesterase, decreasing [cAMP], so protein kinase A is gradually inactivated * Insulin activates protein phosphatase 1, which dephosphorylates glycogen synthase to **glycogen synthase a** * Glycogen synthase a is active, so glycogen is synthesized

Answer 114

**Activators** * AMP (in muscle only) **Inhibitors** * Glucose-6-phosphate * ATP * Glucose (in liver only)

Answer 115

**Activators** * Glucose-6-phosphate (in well-fed state only)

Answer 116

**Calmodulin** * Ca²⁺ is released from the ER in response to hormones or neurotransmitters * Ca²⁺ binds to calmodulin, forming the calmodulin-Ca²⁺ complex * The calmodulin-Ca²⁺ complex activates phosphorylase kinase (without phosphorylation), which activates glycogen phosphorylase * The calmodulin-Ca²⁺ complex activates a calmodulin-dependent protein kinase, which inactivates glycogen synthase **PKC** * Binding of a hormone/neurotransmitter (e.g. epinephrine) to its GPCR stimulates G_αq, which activates phospholipase C * Phospholipase C leads to formation of DAG in the membrane and release of IP₃ * IP₃ leads to release of Ca²⁺ from the ER * Ca²⁺ and DAG activate protein kinase C * Protein kinase C inactivates glycogen synthase

Answer 117

* The ADH/ALDH pathway, producing acetaldehyde or acetate * Microsomal ethanol oxidizing system (MEOS), producing acetaldehyde * Catalase-dependent oxidation, producing acetaldehyde (in the peroxisome)

Answer 118

ethanol + NAD⁺ → acetaldehyde + NADH * Catalyzed by alcohol dehydrogenase (ADH) * Acetaldehyde is toxic

Answer 119

acetaldehyde + NAD⁺ → acetate + NADH * Catalyzed by acetaldehyde dehydrogenase (ALDH) * 90% of acetaldehyde is oxidized this way

Answer 120

Activated to acetyl CoA for use in the Krebs cycle or fatty acid synthesis

Answer 121

* Transport in the blood to the heart and skeletal muscle * acetate + ATP + CoA-SH → acetyl CoA + AMP + PP_i * Catalyzed by acetyl-CoA synthetase

Answer 122

High ratio of NADH to NAD⁺, leading to: * Inhibition of gluconeogenesis * Lactic acidosis * Inhibition of fatty acid oxidation

Answer 123

ethanol + NADPH + H⁺ + O₂ → acetaldehyde + NADP⁺ + 2H₂O * Catalyzed by cytochrome P450 2E1 (CYP2E1), a high K_m enzyme inducible by alcohol * CYP2E1 is a major cause of oxidative stress by producing ROS like H₂O₂, HER∙, O₂∙^–

Answer 124

ethanol + H₂O₂ → acetaldehyde + H₂O * Catalyzed by peroxisomal catalase * Catalase is found in all tissues, but is dependent on cellular levels of hydrogen peroxide * Catalase is also found in cells of the normal flora, leading to acetaldehyde production in the lower GI tract

Answer 125

* ADH, ALDH, and CYP2E1 exist as families of isozymes * ADH exists as 5 isozymes, each produced in a different tissue (e.g. liver, lung, stomach, esophagus) * People inherit different sets of ADH isozymes. E.g. African Americans have an isoform with a high V_max

Carbohydrate metabolism (midterm) Flashcards

(155 cards)