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
2
Q
Synthesis of phosphoenol pyruvate (PEP)
A
Synthesis from pyruvate requires two steps catalyzed by:
- pyruvate carboxylase
- PEP carboxykinase
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
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+
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
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
7
Q
Gluconeogenesis Substrates (3)
A
- Lactate
- Glycerol
- Amino acids
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
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
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
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.
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
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
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
15
Q
Glycogenesis
A
Glycogen synthesis –> occurs when blood glucose levels are high
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
Regulation of Glycogen metabolism
Involves hormones (insulin, glucagon, epinephrine) and allosteric regulation (glycogen synthase and glycogen phosphorylase)
26
Allosteric Regulation of Glycogen metabolism
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
Hormonal regulation of Glycogen metabolism
I dont know
28
Glycogen storage diseases (3)
- 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
Concentration of blood glucose
- Post- absorptive state
- Ingestion of a carbohydrate meal
- starvation
- consequences of a sudden decrease in blood glucose
- 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
Sources of blood glucose (3)
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
Glucokinase (3)
- 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
Glucose tolerance
- definition
- decreased glucose tolerance arises due to:
- 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
Glucosuria (3)
- 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
Glucagon (5)
- 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
Insulin (2)
- 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
Insulin plays a central role
why? (4)
WTF IS THIS, NU EXPLAIN TO ME
- 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
