Gluconeogenesis Flashcards

1
Q

Gluconeogenesis (4)

A
  • formation of new glucose molecules from non- carbohydrates precursors (ex: lactate, pyruvate, glycerol)
  • occurs primarily in the liver
  • when glucogen is depleted, gluconeogenesis provides the body with glucose
  • it is the reverse of glycolysis, except for reactions 1,3,10 –> catalyzed by hexokinase, PFK-1, pyruvate kinase
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2
Q

Synthesis of phosphoenol pyruvate (PEP)

A

Synthesis from pyruvate requires two steps catalyzed by:

  • pyruvate carboxylase
  • PEP carboxykinase
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3
Q

Step 10 of Glycolysis = step in gluconeogenesis (4)

A
  • pyruvate carboxylase, found within mitochondria, converted pyruvate to oxaloacetate
  • Bicarbonate + pyruvate + ATP –> ADP + Pi + Oxaloacetate
  • then oxaloacetate is decarboxylated and pohspohrylated by PEP carboxykinase in a reaction drive by the hydrolysis of guanosine triphosphate (GTP)
  • OAA + GTP –> GDP + PEP + CO2
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4
Q

Malate shuttle (4)

A
  • allows gluconeogenesis to continue because it provides the NADH required for the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase
  • OAA is converted into malate by mitochondrial malate dehydrogenase
  • after malate cross the mitochondrial membrane, the reverse reaction is catalyzed by cytoplasmic malate dehydrogenase

-OAA + NADH + H –> malate + NAD+

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5
Q

Step 7 of Gluconeogenesis = step 3 in glycolysis (4)

A
  • conversion of fructose-1,6-biphosphate to fructose-6-phosphate
  • irreversible
  • fructose-1,6-biphosphate +H20 –> fructose-6-phosphate + Pi
  • enzyme: fructose-1,6- bisphosphatase
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6
Q

Step 10 of Gluconeogenesis = step 1 glycolysis (3)

A
  • enzyme: glucose-6-phosphatase, found in liver and kidney
  • gluconeogenesis is an energy-consuming process, it required the hydrolysis og 6 high- energy phosphate bonds

-Glucose 6- phosphate + H20 –> glucose + Pi

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7
Q

Gluconeogenesis Substrates (3)

A
  • Lactate
  • Glycerol
  • Amino acids
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8
Q

Gluconeogenesis Substrates

-lactate (3)

A
  • released by red blood cells and other cells that lack mitochondria or have low O2 concentrations
  • in cori cycle, lactate is released during exercise
  • after lactate is transferred to the liver, it is reconverted to pyruvate by lactate dehydrogenase and then to glucose by glyconeogenesis
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9
Q

Gluconeogenesis Substrates

-glycerol (3)

A
  • a product of fat metabolism in adipose tissue
  • transported to the liver in the blood and then converted to glycerol-3-phosphate by glycerol kinase
  • oxidation of glycerol-3-phosphate to form DHAP (dihydroxyacetone phosphate) occurs when cytoplasm NAD+ concentrations are high, catalyzed by Glycerol phosphate dehydrogenase
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10
Q

Gluconeogenesis Substrates

-amino acids (4)

A
  • alanine is the most imp
  • pyruvate + L-Glutamate –> L-alanine + a-ketoglutarate
  • transmination reaction
  • enzyme: alanine transaminase
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11
Q

Glucose- alanine cycle (3)

A

-When exercising muscle produces large quantities of pyruvate, some of these molecules are converted to alanine by a transamination reaction involving
glutamate
-alanine transaminase
-After alanine has been transported to the liver, alanine is reconverted to pyruvate and then to glucose.

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12
Q

Gluconeogenesis Regulation (4)

A
  • reciprocally regulated –> when one process takes place the other one is turned off
  • ATP plentiful –> gluconeogenesis predominates
  • ATP scarce –> glycolysis predominates
  • LOOK AT THE PIC AND MEMORIZE EVERYTHING
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13
Q

Gluconeogenesis Hormonal Regulation (3)

A
  • hormones can influence gluconeogenesis by altering enzyme synthesis
  • Insulin depresses –> synthesis of PEP carboxy-kinase, fructose-1,6-biphosphatase, glucose- 6- phosphatase
  • Glucagon stimulates –> synthesis of PEP carboxy-kinase, fructose-1,6-biphosphatase, glucose- 6- phosphatase
  • LOOK AT THE PIC AND MEMORIZE
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14
Q

Glycogen

  • structure
  • function
A
  • is the storage form of glucose
  • contains α-1,4-glycosidic bonds and α-1,6-glycosidic bonds
  • in muscle –> serves as fuel source for the generation of ATP
  • in liver –> serve as a source of blood glucose
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15
Q

Glycogenesis

A

Glycogen synthesis –> occurs when blood glucose levels are high

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16
Q

Glycogenesis

-Step 1 (4)

A
  • synthesis of glucose-1-phosphate
  • reversible
  • enzyme: phosphoglucomutase
  • glucose-6-phosphate –> glucose-1,6-biphosphate –> glucose-1-phosphate
17
Q

Glycogenesis

-Step 2 (3)

A
  • synthesis of uridine diphosphate-glucose (UDP-glucose)
  • enzyme: pyrophosphorylase
  • glucose-1-phosphate –> uridine diphosphate-glucose
18
Q

Glycogenesis

-Step 3 (2)

A
  • synthesis of glycogen from uridine diphosphate- glucose

- requires two enzymes: glycogen synthase and amylo-α (1,4 –> 1,6) glucosyl transferase (branching enzyme)

19
Q

What does glycogen synthase and amylo-α (1,4 –> 1,6) glucosyl transferase do?

A

Glycogen synthase –> catalyzes the transfer of the glucosyl group of UDP- glucose to the nonreducing ends of glycogen

Amylo-α (1,4 –> 1,6) glucosyl transferase –> creates the α(1,6) linkages for branches in the molecule

20
Q

Glycogen synthesis requires…….?

A
  • a pre-existing tetra saccharide composed of 4 α (1,4) - linked glucosyl residues
  • the first residue is linked to a “primer” protein called glycogenin
21
Q

Glycogenolysis

A
  • glycogen degradation
  • two reactions: removal of glucose from the nonreducing ends of glycogen and hydrolysis of the α(1,6) glycosidic bonds at branch points of glycogen
22
Q

Glycogenolysis

-Step 1 (4)

A
  • removal of glucose from the nonreducing ends of glycogen
  • enzyme: glycogen phosphorylase
  • the enzyme uses inorganic phosphate to cleave the α(1,4) linkages on the outer branches of glycogen to yield glucose- 1- phosphate
  • the enzyme stops when it comes within 4 glucose residues of a branch point
23
Q

Glycogenolysis

-Step 2 (4)

A
  • hydrolysis of the α(1,6) glycosidic bonds at branch points of glycogen
  • amylo α(1,6)- glucosidade (debranching enzyme), begins removal by transferring the outer 3 of the 4 glucose residues attached to the branch point to a nonreducing end
  • it then removes the single glucose residue attached at each branch point
  • product: free glucose
24
Q

Glycogenolysis

-the end (4)

A
  • glucose- 1- phosphate is converted in the cytosol to glucose-6-phosphate by phosphoglucomutase
  • in the liver, glucose-6-phosphate is transported to ER by glucose-6-phosphate translocase
  • it is converted to glucose by glucose-6-phosphatase
  • glucose moves to the cytosol
25
Q

Regulation of Glycogen metabolism

A

Involves hormones (insulin, glucagon, epinephrine) and allosteric regulation (glycogen synthase and glycogen phosphorylase)

26
Q

Allosteric Regulation of Glycogen metabolism

A

Glycogen synthase –> glucose-6-phosphate is a positive allosteric regulator

Glycogen phosphorylase:

  • high amounts of free glucose (ONLY IN THE LIVER) –> negative
  • glucose-6-phosphate –> negative
  • large amounts of ATP –> negative
  • AMP (ONLY IN THE MUSCLES) –> positive
27
Q

Hormonal regulation of Glycogen metabolism

A

I dont know

28
Q

Glycogen storage diseases (3)

A
  • genetic diseases caused by defects in enzymes required for glycogen degradation or synthesis
  • consequences: formation of glycogen that has an abnormal structure and accumulation of excessive amounts of normal glycogen in tissues
  • ex: Cori’s –> debranching enzyme deficiency –> altered glycogen structure, hypoglycemia
29
Q

Concentration of blood glucose

  • Post- absorptive state
  • Ingestion of a carbohydrate meal
  • starvation
  • consequences of a sudden decrease in blood glucose
A
  • 4.5-5.5 mmol/L
  • 6.5-7.2 mmol/l
  • 3.3-3.9 mmol/L
  • convulsions, because of the dependence of the brain on a supply of glucose
30
Q

Sources of blood glucose (3)

A

1- the digestible dietary carbohydrates yield glucose, galactose and fructose
2- glucose is formed from two groups of compounds that undergo gluconeogenesis (a direct net conversion to glucose and those which are the products of the mtabolsim of glucose in tissues)
3-glucose is also formed from liver glycogen by glycogenolysis

31
Q

Glucokinase (3)

A
  • important after a meal
  • has a high Km (low affinity) for glucose
  • its activity increases with increases in the concentration of glucose in the hepatic portal vein
32
Q

Glucose tolerance

  • definition
  • decreased glucose tolerance arises due to:
A
  • the ability to regulate the blood glucose concentration after the administration of a test dose glucose
  • decreased secretion of insulin and impaired sensitivity of tissues to insulin action
33
Q

Glucosuria (3)

A
  • occurs when the venous blood glucose concentration exceeds about 10mmol/L
  • when kidneys may not take enough blood sugar out of your urine before it passes out of your body.
  • the renal threshold for glucose
34
Q

Glucagon (5)

A
  • produced by α cells of the pancreatic islets
  • secretion is stimulated by low blood sugar
  • in liver it sitmulates glycogenolysis by activatinh phosphorylase
  • enhances gluconeogenesis from amino acids and lactate
  • increased glycogenolysis and gluconeogenesis –> hyperglycemic effect of glucagon
35
Q

Insulin (2)

A
  • lowers blood glucose by enhancing glucose transport into adipose tissue and muscle recruitment of GLUT-4
  • produced by the β cells of islets of Langerhans in the pancreas in response to high blood sugar
36
Q

Insulin plays a central role
why? (4)

WTF IS THIS, NU EXPLAIN TO ME

A
  • β cells are freely permeable to glucose via GLUT2 transporter and the glucose is phosphorylated by glucokinase
  • high blood glucose increases the rate of glycolysis, citric acid cycle, generation of ATP
  • high ATP inhibits ATP sensitive K+channels causing depolarization of the cell membrane,and stimulates exocytosis of insulin
  • THE CONCENTRATION OF INSULIN IN THE BLOOD PARALLELS THAT OF THE BLOOD GLUCOSE