Lecture 10
Introduction to Nutrition and Metabolism
Overview
Presentation from The University of Strathclyde
Course code: BM210, Instructor: Dr. Martin Wiese
Reference Text:
Title: Introduction to Nutrition and Metabolism, 3rd edition
Author: David A Bender
Publisher: Taylor & Francis Ltd, London 2002
Additional Reference: Biochemistry, 10th edition by Berg, Gatto, Hines, Tymoczko, Stryer, 2023, Macmillan Learning
Learning Outcomes
Understand the following:
Glycogenolysis - the breakdown of glycogen to glucose.
Gluconeogenesis - the synthesis of glucose from non-carbohydrate precursors.
Regulatory function of fructose-1,6-bisphosphatase - an important enzyme in gluconeogenesis.
Cori Cycle and Glucose-Alanine Cycle - metabolic pathways linking muscle and liver.
Molecules that can be used to synthesize glucose - including amino acids, glycerol, lactate, and propionate.
Importance of fats in the diet - with emphasis on dietary triglycerides and essential fatty acids.
Breakdown of triacylglycerols to fatty acids.
The process of β-oxidation of fatty acids.
Part A: Fat Breakdown
Post-Absorptive State
Refers to a physiological state where the body begins to depend on stored energy reserves after the absorption of nutrients.
Key processes include:
Glycogen Breakdown
Triglyceride Breakdown
Gluconeogenesis
Fatty Acids as Metabolic Fuel
Dietary Fat Requirements
There is no absolute requirement for fat in the diet, with exceptions for two essential polyunsaturated fatty acids:
Linoleic acid (C18:2)
Linolenic acid (C18:3)
Functions of Dietary Fat
Lipid-soluble vitamins A, D, E, and K are present in fats and require fat for absorption.
Fat aids in:
Lubricating food in the mouth
Contributing to the flavor of food
Types of Fats in Diet and Body
Major Classifications
Triacylglycerols (Triglycerides)
Composed of three fatty acids attached to glycerol.
Phospholipids
Composed of two fatty acids and a head group attached to glycerol.
Cholesterol
A four-ring hydrocarbon structure.
Fatty Acid Structure
Saturated Fatty Acids
Contain no double bonds.
Unsaturated Fatty Acids
Contain one or more double bonds (e.g., C16:0, C18:0, C18:1).
Digestion of Fat
Lipases are enzymes responsible for the digestion of fats, including:
Lingual lipase
Gastric lipase
Pancreatic lipase and phospholipase
Absorption occurs for fatty acids and glycerol in the digestive tract.
Lipid Uptake and Transport
Lipids, being hydrophobic, require special methods for circulation in the body.
Lipoproteins serve as transport vehicles.
In the intestine, triacylglycerols and cholesterol are repackaged into low-density lipoproteins (LDL).
Transport involves emulsion and re-esterification into chylomicrons with apolipoprotein B-48.
Chylomicrons deliver triacylglycerols to adipose and peripheral tissues, followed by the release of fatty acids into the bloodstream.
Fatty Acid Oxidation - β-Oxidation
Steps in β-Oxidation
Activation
Formation of a thioester bond between fatty acid and CoA facilitated by acyl-CoA synthetase.
Requires ATP hydrolysis.
Oxidation
Removal of 2 H atoms forming a double bond.
Hydration
Addition of H2O across the double bond.
Oxidation
Conversion of alcohol group to a ketone group (C=O).
Thiolysis
Cleavage of acetyl-CoA from the activated end.
Energy Yield from Fatty Acid Oxidation
For palmitate (C16:0), the yield is calculated as follows:
Each cycle of β-oxidation produces 14 ATP, with breakdown as follows:
NADH contributes approximately 2.5 ATP.
FADH2 contributes approximately 1.5 ATP.
Acetyl CoA contributes approximately 10 ATP via the TCA cycle.
7 cycles of oxidation are required for palmitate, leading to a total yield equation of:
Degradation of Unsaturated Fatty Acids
Requires additional enzymes:
Cis-D3-Enoyl CoA isomerase for one double bond.
Cis-D3-Enoyl CoA isomerase and 2,4-Dienoyl CoA reductase for two double bonds.
Degradation of Odd Chain Fatty Acids
Results in the production of propionyl CoA (3C), which can be converted to succinyl CoA to enter the TCA cycle.
Key Concepts
Types of fats
Uptake and degradation of fats, including lipases and β-oxidation.
Part B: Gluconeogenesis
Overview of Gluconeogenesis
The conversion of pyruvate to glucose occurs primarily in the liver.
Non-carbohydrate precursors that can participate include:
Lactate, produced when glycolysis exceeds oxidative metabolism.
Amino acids, from protein breakdown.
Propionate and Glycerol, from the hydrolysis of triacylglycerols.
Key Enzymatic Steps in Gluconeogenesis
Replace irreversible steps of glycolysis with gluconeogenic enzymes:
Hexokinase (catalyzes the phosphorylation of glucose).
Fructose-1,6-bisphosphatase (catalyzes dephosphorylation of fructose-1,6-bisphosphate).
Pyruvate carboxylase and phosphoenolpyruvate carboxykinase (PEPCK) (catalyzes conversion of pyruvate to phosphoenolpyruvate).
Function of Key Enzymes
Glucose-6-phosphatase:
Catalyzes the conversion of glucose-6-phosphate to glucose, releasing inorganic phosphate (Pi) and requiring H2O.
Found mainly in the liver and kidney for regulation of blood glucose levels.
Enzyme Structure Requirements
Five proteins are needed for glucose-6-phosphate transformation into glucose.
Pathways of Oxaloacetate Conversion
Mitochondrial oxaloacetate can be converted via three pathways to become cytosolic:
Reduction to malate.
Transamination to aspartate.
Conversion to phosphoenolpyruvate (PEP) via mitochondrial PEPCK.
Pyruvate Carboxylase Function
Localized in mitochondria and carries biotin as a prosthetic group.
Catalyzes the transfer of an activated carboxyl group to pyruvate, converting it to oxaloacetate.
Acetyl CoA acts as an allosteric activator of pyruvate carboxylase.
Phosphoenolpyruvate Formation
Oxaloacetate undergoes decarboxylation and phosphorylation to form phosphoenolpyruvate, and this reaction is inhibited by ADP.
Importance of Decarboxylation Reactions
Carboxylation leading to phosphoenolpyruvate is critical due to the unfavorable energetic cost of direct phosphorylation of pyruvate.
for direct phosphorylation.
The coupled reactions via carboxylation and decarboxylation reduce this to .
Key Terms
Carbohydrate and non-carbohydrate precursors of gluconeogenesis
Reactions of gluconeogenesis
Activated carboxyl group process
Fate of oxaloacetate in gluconeogenesis
Role of decarboxylation reactions
Part C: Cori Cycle and Glucose-Alanine Cycle
Description of Cycles
Both cycles facilitate energy supply to tissues requiring glucose.
Tissues release lactate or alanine instead of fully oxidizing glucose.
The Cori Cycle
Gluconeogenesis from lactate is energy-intensive. Requires 6 ATP to convert lactate to glucose, while only 2 are generated through anaerobic glycolysis, creating a net loss of 4 ATP per cycle.
ATP needed for glucose synthesis is usually provided by fatty acid oxidation.
The Glucose-Alanine Cycle
Muscles transaminate pyruvate to alanine (with the help of alanine transaminase) which then returns to the liver for gluconeogenesis.
Lipids in Gluconeogenesis
Fatty acids cannot be converted to glucose, but glycerol can.
Glycerol is phosphorylated into glycerol-3-phosphate and then converted through dihydroxyacetone phosphate.
Key Concepts of Glycogen Breakdown
Glycogenolysis requires four enzymes:
Glycogen phosphorylase
Glucosyl transferase
a-1,6-glucosidase
Phosphoglucomutase
Importance of Phosphorolysis Over Hydrolysis
Phosphorolysis yields glucose-1-phosphate, which is directly usable in glycolysis, while hydrolysis would require further ATP expenditure to phosphorylate glucose.
Challenges in Glycogen Breakdown
Glycogen phosphorylase cannot cleave a-1,6-glycosidic bonds effectively at branch points.
Summary of Key Terms
Cori cycle, Glucose-Alanine cycle
Amino acids and lipids in gluconeogenesis
Glycogenolysis process and significance of phosphorolysis