Download PHARMACY BIOMEDICAL PREVIEW PROGRAM 2014

GLUCONEOGENESIS
SAFIYA RANSOME, P3 ([email protected])
PHARMACY BIOMEDICAL PREVIEW PROGRAM 2014
Gluconeogenesis: Introduction
• Gluconeogenesis is an anabolic process that produces
glucose from non-carbohydrate precursors. Glycerol
Lactate
Amino Acids
Glucose
Gluconeogenesis
• Occurs primarily in the liver and somewhat in the kidney;
overall, helps to maintain adequate blood glucose level
so that tissues can meet metabolic demands.
• Gluconeogenesis is NOT the reverse of glycolysis. Gluconeogenesis is NOT
glycolysis in reverse!
• Remember, three of the steps of glycolysis were
irreversible. These steps are thermodynamically
favored. (Produce a net decrease in free energy,
ΔG.)
• Gluconeogenesis has three of it’s own irreversible
steps that bypass the irreversible steps of
glycolysis. (These are the steps that we will
examine in depth!)
Gluconeogenesis Overview
End Here! ➜
Start Here!
Entering the Pathway
• The various non-carbohydrate precursors are modified so
that they may enter the gluconeogenesis pathway at
different points. • Lactate is converted into pyruvate by lactate
dehydrogenase. Pyruvate enters the pathway.
• Glucogenic amino acids are converted into either
pyruvate or oxaloacetate before entering the pathway. • Glycerol is converted into DHAP before entering the
pathway.
Glycolysis vs. Gluconeogenesis
• To overcome the thermodynamic constraints, the
irreversible steps of glycolysis are bypassed in the
gluconeogenesis pathway.
Glycolysis Step
Pyruvate Kinase
Gluconeogenesis Step
1.
2.
Pyruvate carboxylase
Phosphoenolpyruvate
carboxykinase
Phosphofructokinase
Fructose-1,6-bisphosphatase
Hexokinase
Glucose-6-phosphatase
Pyruvate Carboxylase
• Converts pyruvate to oxaloacetate
Phosphoenolpyruvate
Carboxykinase
• Converts oxaloacetate to phosphoenolpyruvate
Fructose-1,6-bisphosphatase
• De-phosphorylates Fructose-1,6-bisphosphate to
produce Fructose-6-phosphate
Glucose-6-phosphatase
• De-phosphorlyates glucose-6-phosphate to
produce glucose
Regulating Glycolysis
and Gluconeogenesis
• Gluconeogenesis and glycolysis are coordinated so
that, within a cell, one pathway is relatively inactive
while the other is highly active.
• This principle is known as Reciprocal Regulation.
• The predominately active pathway is decided by the
cellular energy charge.
• Cell Energy Deficit ➜ Glycolysis active
• Cell Energy Surplus ➜ Gluconeogenesis active
CITRIC ACID CYCLE
(TCA CYCLE, KREB’S CYCLE)
PHARMACY BIOMEDICAL PREVIEW PROGRAM 2014
Citric Acid Cycle
• Also known as the Tricarboxylic Acid (TCA) Cycle and the Kreb’s
Cycle. • Primary Function: to harvest high energy electrons from carbon
fuels. Electrons are stored in the form of NADH and FADH2. • NADH and FADH2 are later converted into ATP by oxidative
phosphorylation via the electron transport chain.
• Acetyl-CoA is the primary fuel for the citric acid cycle. • Other fuels can enter the cycle at different points. • Very little ATP is produced— just one molecule.
Citric Acid Cycle: Overview
Bridging the Gap:
From Glycolysis to TCA Cycle
• Recall that the final molecule produced by the
glycolysis pathway is pyruvate and that the primary
fuel of the citric acid cycle is acetyl-CoA. • The Pyruvate Dehydrogenase Complex converts
pyruvate to Acetyl-CoA. This step is not considered
a part of glycolysis or the citric acid cycle.
Citric Acid Cycle:
Important Steps
• Produce NADH
• Isocitrate Dehydrogenase (+ CO2 as well)
• α-ketoglutarate dehydrogenase complex (+ CO2 as well)
• Malate dehydrogenase
• Produce FADH2
• Succinate dehydrogenase
• Produce ATP
• Succinyl-CoA Synthetase
Tallying the Products
• For one complete turn of the citric acid cycle (with
input of 1 mol of Acetyl-CoA): • 3 NADH produced
• 1 ATP produced
• 1 FADH2 produced
• 2 CO2 produced
PENTOSE PHOSPHATE PATHWAY
PHARMACY BIOMEDICAL PREVIEW PROGRAM 2014
Pentose Phosphate Pathway
• Primary function: To produce NADPH and
ribose-5-phosphate.
• Glycolysis is linked: Glucose-6-phosphate
(produced by hexokinase) is the entry molecule for
this pathway. • Occurs in the cytosol (plasma membrane) • Alternate names: pentose shunt, hexose
monophosphate shunt, phosphogluconate pathway.
Primary Products
• NADPH
• A reducing molecule used in various anabolic biosynthesis
pathways. NADPH also protects the cell from oxidative stress. • vs NADH? NADH is used in catabolic pathways.
• Used in fatty acid biosynthesis, cholesterol biosynthesis, and
nucleotide biosynthesis. • Ribose-5-Phosphate
• Used in the production of RNA, DNA, and nucleotide
+
coenzymes (such as CoA, FAD, NAD, NADP )
Pentose Phosphate Pathway
Pentose Phosphate Pathway
• Consists of two phases:
• Oxidative Phase:
• NADPH is generated when glucose 6-phosphate is oxidized to
ribulose 5-phosphate, which is subsequently converted into
ribose 5-phosphate.
• Non-oxidative Phase:
• Pathway catalyzes the interconversion of three-, four-, five-, six-,
and seven-carbon sugars in a series of nonoxidative reactions.
• Five carbon sugars produced via interconversion can then enter
into the glycolyic pathway.