NUTR 3210 Lecture Notes - Lecture 4: Pentose Phosphate Pathway, Pyruvate Dehydrogenase Complex, Uridine Diphosphate
1 May 2018
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NUTR3210 – Review of Intermediary Metabolism
Learning Outcomes:
• Describe glycolysis
• Describe glycogen formation and breakdown
• Describe pyruvate dehydrogenase complex and citric acid cycle (TCA)
• Describe ETC
• Describe gluconeogenesis
• Describe hexose monophosphate shunt
• Discuss the interactions between these processes and the conditions that favour or
inhibit the different routes of metabolism
Metabolism Summary:
• Metabolism can be divided into anabolism (energy is used to build tissues) and
catabolism (energy produced and liberated from tissue stores)
• Molecules that are broken down for energy production = catabolic
o Glycogen Glucose
o Triglycerides fatty acids
o Protein amino acids
*moves in opposite direction when reaction is anabolic
• Nutrient building blocks will be used to synthesize new proteins, lipids and
polysaccharides (replenishing and forming new cells/ tissue structures)
*See summary of pathways
Focus on:
• Purpose of each pathway (key steps and enzymes)
• Starting and ending points
• Energetics of each pathway
• Conditions that make each pathway more or less active
• The tissues and cellular/subcellular locations for pathways
• How pathways are integrated in metabolism
Metabolic Fates of Glucose:
• 6C Glucose glucose-6-phosphate (phosphorylation traps glucose in the cell)
• glucose-6-phosphate glucose-1-phosphate / fructose-6-phosphate / 6-
phosphogluconate
o glucose -1 phosphate glycogen (energy is stored as glycogen)
o fructose-6-phosphate 3C pyruvate 2C acetyl CoA (through pyruvate
dehydrogenase reaction)
▪ Acetyl CoA goes into the TCA for energy production (catabolic) or
is used to make fatty acids which are made into triglycerides
(energy is stored as fat; anabolic)
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o 6-phosphogluconate **pentose phosphates + NADPH (anabolism)
**Hexose Monophosphate Shunt
• pentose phosphates (5-carbon monosaccharides) + NADPH
• ribose-phosphates (5C) needed for DNA and RNA formation
Regulation of Blood Glucose:
• Insulin and glucagon are the hormones that regulate the concentration of glucose
in the
o Change from glucose to glycogen (or the other way) occurs in the liver
• Hormones are produced in the pancreas
o Insulin from beta cells; Glucagon from alpha cells
• Insulin:
o Released when blood glucose concentration is high
o Stimulates glucose uptake and storage (as glycogen) by peripheral tissues
glycogenesis
• Glucagon:
o Released when blood glucose concentration is low
o Stimulates the breakdown or catabolism of glycogen stores
glycogenolysis
Glycogenesis:
• Purpose: synthesize glycogen
• Tissue/Location: Liver, muscle (cytosol)
• Hormone Regulation: Insulin
• Type of Metabolism: anabolic
• Energy: uses 2 ATP equivalents (2 high energy phosphates expended per glucose
molecule that is stored as glycogen)
• Steps:
o Glucose glucose-6-phosphate
▪ Hexokinase in muscle; glucokinase in the liver
o Glucose-6-phosphate glucose-1-phosphate
o Glucose-1-phosphate + UTP(uridine-5-triphosphate) UDPG (uridine
diphosphate glucose)
▪ UTP is ATP equivalent
o UDPG + glycogen primer (with n glucose) glycogen (n+1) + UDP
▪ Glycogen synthase + branching enzyme
▪ At the same level, UDPG + H2O 2Pi (from UTP and g-1-P)
• Glucokinase is not inhibited by high glucose-6P; hexokinase is not!
o Liver continues to take up and phosphorylate glucose when blood levels
are high
Glycogenolysis:
• Purpose: breakdown glycogen glucose
• Tissues/Location: Liver, muscle (cytosol)
find more resources at oneclass.com
find more resources at oneclass.com
• Hormone Regulation: Glucagon
• No energy requirement
• Type of Metabolism: Catabolic
• Steps:
o Glycogen (n) + Pi glucose-1-phosphate
▪ Glycogen phosphorylase and debranching enzyme
o Glucose-1-phosphate + glycogen (n-1) glucose-6-P
▪ *in muscle, glucose-6P committed to glycolysis; no release of
glucose into the blood by muscles
o Glucose-6-phosphate + H2O glucose
▪ Glucose-6-phosphatase (only in the liver)
o Glucose then enters the blood stream
Control of Blood Glucose by Glycogenesis and Glycogenolysis:
• Glucagon stimulates liver glycogenolysis and the release glucose into the blood
• Insulin stimulates the uptake of glucose by muscle and liver which in stores and
glycogen = glycogenesis
• “figure 8” within the body (see slide)
Sites of Energy Capture as ATP
There are two ways to generate ATP in a cell:
1. Substrate-Level: formation of ATP (or equivalent) is coupled to the conversion of
substrate to product *important under low oxygen conditions
• Ex. PO3 is captured as a high energy bond in ATP
R-OPO32- R-OH; producing ATP from ADP
• Occurs in the mitochondria (TCA/Krebs) and cytoplasm (glycolysis)
2. Oxidative Phosphorylation: ATP is synthesized from ADP and inorganic
phosphate by ATP synthase
• Uses an H+ proton gradient ; E.g. in ETC
• Occurs in the presence of reducing equivalents (NADH/FADH2) and
oxygen
• High efficiency ATP production
• ATP synthase (transmembrane protein) moves H+ from a high to low
gradient
Reducing Equivalents:
• Transfers the equivalent of one electron in redox reactions
• Oxidation = loss of electrons (or energy)
• Reduction = gain of electrons (or energy)
• NAD (oxidized state) accepts 2 electrons and can bind one proton
• FAD (oxidized state) accepts 2 electrons and binds 2 H+
Glycolysis
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
*moves in opposite direction when reaction is anabolic: nutrient building blocks will be used to synthesize new proteins, lipids and polysaccharides (replenishing and forming new cells/ tissue structures) **hexose monophosphate shunt: pentose phosphates (5-carbon monosaccharides) + nadph ribose-phosphates (5c) needed for dna and rna formation. Insulin: released when blood glucose concentration is high, stimulates glucose uptake and storage (as glycogen) by peripheral tissues. Glycogenesis: glucagon, released when blood glucose concentration is low, stimulates the breakdown or catabolism of glycogen stores. Control of blood glucose by glycogenesis and glycogenolysis: glucagon stimulates liver glycogenolysis and the release glucose into the blood. Insulin stimulates the uptake of glucose by muscle and liver which in stores and glycogen = glycogenesis: figure 8 within the body (see slide) There are two ways to generate atp in a cell: substrate-level: formation of atp (or equivalent) is coupled to the conversion of substrate to product *important under low oxygen conditions, ex.
