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Exam 1 Information > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

What is gluconeogenesis?

A

Net formation of glucose from pyruvate

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2
Q

Gluconeogenic enzymes

A
  • Glucose 6 phosphatase
  • Fructose-1,6 bisphosphatase
  • Pyruvate carboxylase and PEP carboxylase
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3
Q

Location of first bypass (Pyruvate carboxylase+ATP)

A

Mitochondria

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4
Q

Pyruvate carboxylase

A

Dissolved CO2 present in the bloodstream and within cells as bicarbonate ions are used
Enzyme contains biotin covalently bound to lysine residue
Other cofactors: Mg++, K+ and ATP

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5
Q

Intermediate in Step 1

A

Oxaloacetate exits mitochondria– after it is converted to aspartate– via the malate-aspartate shuttle.

In cytosol, it converts back to oxaloacetate

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6
Q

Other molecules can be gluconeogenic?

A

yes. Cytosolic oxaloacetate from other sources (for example, breakdown of amino acids in the cytosol) can be gluconeogenic

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7
Q

Location of PEP carboxylase (+GTP)?

A

Primarily in the cytosol

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8
Q

Requirements of PEPCK?

A

Mn++, K+, and GTP

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9
Q

Fructose-1,6-bisphosphate

  • Stimulators vs Inhibitors
  • When does it operate?
A
  • ALlosteric inhibitors: Fructose-2,6 bisphosphate
  • Stimulators: ATP and citrate
  • Operates effctively in resting muscle when [ATP] is high and [ADP, AMP] are low
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10
Q

Glucose-6-phosphate

A

-Converts glucose-6-phosphate to glucose

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11
Q

If ATP/ADP is high, oxaloacetate is used for…

If ATP/ADP is low, oxaloacetate is used for…

A

If ATP/ADP is high, oxaloacetate is used for gluconeogenesis

If ATP/ADP is low, oxaloacetate is used for… TCA cycle

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12
Q

Activation of pyruvate carboxylase

A

Activated in the presence of Acetyl CoA

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13
Q

Primary site for gluconeogenesis

A

Liver

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14
Q

All the steps of gluconeogenesis occurs in the cytoplasm except…

A

Transformation of pyruvate to oxoaloacetate— occurs in the mitochondria

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15
Q

Glucose-6-phosphate

A
  • Located in the lumen of the endoplasmic reticulum
  • Present in liver, kidney medulla
  • Absent in other tissues, especially the CNS and erythrocytes where glucose is the primary fuel
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16
Q

Allosteric stimulator of gluconeogenesis

A

ATP, citrate, acetyl CoA

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17
Q

Fatty acids and gluconeogenesis

A

Fatty acid oxidation provides energy for gluconeogenesis

-During “fasting state”- blood glucose drops, liver can metabolize triglycerides thus providing acetyl CoA and ATP

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18
Q

Glucogenic and metabolic intermediates

A

Glucogenic metabolites supply carbon for gluconeogenesis

  • Carbohydrates if conerted to glycolytic intermediates
  • Almost all amino acids when degraded, they yield TCA intermedoates
  • some TCA intemediates– alpha ketoglutarate, succinyl CoA, oxaloacetate
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19
Q

Lactic Acidosis

A

blood lactate level exceeds 2mM. Lactic Acid diffuses into the bloodstream
-Failure of gluconeogenesis,

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20
Q

Cori cycle between erythrocytes and liver

A

In erythrocytes, pyruvate is converted to lactate by lactate dehydrogease
-Lactate is transported to the liver, where it is converted to pyruvate by LDH and used for gluconeogenesis

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21
Q

Metabolism of Ethanol

A

Inhibits Glucogenesis

Ethanol ->Acetaldehyde ->Acetate+ NADH

  • catalyzed by aldehyde dehydrogenase in the mitochondrial matrix
  • acetate can be converted to acetyl-coA by thiokinase
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22
Q

Thiokinase

A

used to convert actetate to Acetyl-CoA during metabolism of ethanol

Acyl CoA synth Synthetase

23
Q

Effects of ethanol metabolism on liver metabolism

A

Accumulation of NADH within hepatocytes
-Decreased liver NAD+ inhibits both gluconeogenesis from lactate, and fatty acid oxidation (both require NAD+ and produce NADH)

Result in increase in ratio of lactate/pyruvate (shifted to lactic acidosis)

  • Also increase in malate/oxaloacetate ratio
  • Because fatty acid oxidation is inhibited, triglyceride fats accumulate in the lier
24
Q

What is glycogen metabolism?

A

Storage form of glucose that is

  • osmotically stable, as compared to free glucose
  • can be quickly mobilized
  • can be used for energy generation even in the absence of oxygen
25
Q

Glycogen synthesis is poceeded by:

A

“Activation” of glucose to form UDP-glucose which is then utilized to couple glucose residues to a growing glycogen polymer

26
Q

Glycogen synthase

A

Adds glucose residues from UDP-glucose ot the growing polymer, to form glycogen

-C1 end of the incoming glycogen rsidue reacts with C-4 of a glucose residue already on the chain, forming a alpha 1,4glycosidic linkage

Glycogen granule begins with the addition of a molecule of glucose (from UDP-glucose) to the carrier protein glycogenin using a specific glucose transferase enzyme
This takes place immediately after glycogenin protein synthesis
Glycogenin, acting as an enzyme, then appears to self-catalyze the addition of six or seven more glucose units.

Glycogen synthase continues to add glucose residues to hte glycoside chain which is on the glycogenin molecule. When the alpha 1,4-glycoside (amylose) chain reaches at least 11 residues, it then becomes a substrate for the branching enzyme, which removes a block of six or seven glucose residues and transfers it to a neighboring chain in an alpha 1,-6 glycosidic linkage

27
Q

UDP-glucose synthesis

A

Glucose -> Glucose-6-phosphate (using hexokinase)

Glucose-6-Phosphate -> Glucose-1-phosphate (using phosphoglucomutase)

glucose-1-P +UTP -> UDP-glucose + PPi (pyrophosphate)

28
Q

Glycogenolysis

A

Accomplished by the action of the enzyme glycogen phosphorylase, which cleaves 1,4-glycosiic bond by phosphorolysis, beginning at the C-6 ends of the glucose, releasing glucose 1-phosphate

29
Q

What activates glycogenolysis

A

The reaction is activated allosterically by AMP and in glucose and ATP

30
Q

Phosphoglucomutase

A

Glucose-1-P is converted to glucose-6-P by phospoglucomutase and may enter the glycolytic pahtway or be de-phosphorylated (in liver)

Also changes Glucose-1-phosphate to glucose-6P

31
Q

Debranching enzyme

A

Transfers 4 glucose residues from each branch to an adjacent branch, the enzyme can then remove the residue at the branch point by hydrolysis, releasing glucose

32
Q

Glyconeolysis in muscles

A

In muscles, the object of glycogenolysis is production of glucose-6-phosphate for immediate use in the production of ATP.

33
Q

Glyconeolysis in the liver

A

In the liver, the action of glucose-6-phosphatase can lead to the release of glucose into the bloodstream in order to maintain adequate blood glucose concentration

34
Q

Glycogen phosphorylase

A

Enzyme

Catalytic site contains pyridoxal phosphate (Vitamin B6)

Phosphorylated by phosphorylase kinase

Glycogen phosporylase is activated through phosphorylation by the enzyme phosporylase kinase (the active, phosphorylated form is phosporylase a)

The dephospho-form (phosphorylase b) is inactive

35
Q

What is an allosteric inhibitor of glycogen phosphorylase?

What activates glycogen phosphorylase?

A

Glucose inhibits

AMP phosphorylates

36
Q

Phosphorylase kinase

A

-large, multi-submit complex of the form alpha4, beta4, gamma4, delta4)

gamma subunit has catalytic activity

Others are regulatory subunits, which contain sites for phosphorylation

alpha and beta phosphorylated by protein kinase a

37
Q

Glucagon/epinephrine, insulin and glycogenolysis

A

Glucagon and epinephrine, which raise the level of cAMP promotes glycogenolysis

Insulin activates protein phosphatase, leading to a a decrease in cAMP, and inhibiting glycogen phosphorylase

38
Q

Regulation of glycogen synthase– G6P and phosporylation

A

G6P is an allosteric activator of glycogen synthase

GS isozyme is expressed in specific tissue:
-Muscle, kidney, intestinal mucosa
G6P is an allosteric activator of glycogen synthase

Regulated by phosphorylation

  • The phosphorylated form is known as a synthase b, and is less active. Very sensitive to Glu-6-P
  • stimulated by many kinases, including glycogen synthase kinase-3 and protein kinase a
  • aided by glucagon and messenger molecules, cyclic AMP, calcium, diacylglycerol

Dephospho form, synthase a, is fully ctive and is less sensitive to Glu-6-P
-stimulated by insulin

39
Q

Glycogen degredation

A

Stimulated by glucagon and epinephrine

40
Q

Cyclin AMP

A

Activates protein kinase A, which results in the phosphorylation (and activation) of glycogen
phosphorylase as well as phosphorylation (and inactivation) of glycogen synthase. The overall result is
the mobilization of glucose. When the glucose concentration rises sufficiently, the phosphoprotein
phosphatase(s) cause dephosphorylation of regulatory enzymes and the process is reversed. (Here the
action of insulin comes into play.) Thus, at high glucose concentration in liver and in muscle (and
some other tissues), glycogen may be synthesized.

41
Q

Glycogen is primarily stored

A

In liver and muscle

42
Q

Glycogen granule consists of:

A

Glucose linked to carrier protein glycogenin by glucose transferase

43
Q

Where are glycogen granules made?

A

In the ER

44
Q

What activates G-6-Phosphotase?

A

Fructose-6-Phosphate

45
Q

Phosphoglucomutase

A

Converts Glucose-1-P to glucose-6-P

46
Q

Lactose is hydrolized in

A

The small intestine

47
Q

Fructose is broken down in

A

the liver

48
Q

Fructose is transferred by

A

GLUT-4

49
Q

Lactose is transported by

A

GLUT-2

50
Q

Galatose is phosphorylated by

A

lactokinase

51
Q

Galactose is channeled into glucose metabolism in the following steps:

A 
Galactose 1-P
UDP-Galactose
UDP-Glucose
Glucose-1-P
Glucose-6-P
52
Q

Galactosemia

A

Results from deficiencyof galactos uridyl transferase

can lead to high blood levl of galactose

liver failure

53
Q

Galactisol

A

Lack of galactokinase causes accumulation of galactose, which can be reduced to galactisol. Accumulation of galactisol in the lens may lead to early cataract formation

54
Q

Sorbitals and diabetes

A

in tissues of diabetic individuals aldose reductase is induced by elevated glucose level and production of sorbitol can exceed the capacity of sorbitol dehydrogenase.
- Accumulation of sorbitol crystals in some tissues causes pathology: especially in the eye (lens) and kidney (glomerulus)
- Reduction of galactose to galactitol by aldose reductase may produce
similar pathology in individuals with galactosemia

Exam 1 Information (14 decks)

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