Lecture 7 - Nutrition and Metabolism

Name: Lecture 7 - Nutrition and Metabolism
Uploaded: 2020-08-20T22:10:53.000Z
Duration: 2 h 58 min 24 s

Introduction to Nutrition and Metabolism

Overview of Survival Requirements

Dr. Mike introduces the essential elements for human survival: oxygen, water, and nutrients.

Without oxygen, survival is limited to a few minutes; without water, only a few days; and without nutrients, typically no more than 90 days.

Definition of Nutrients

A nutrient is defined as a substance or chemically defined component of food necessary for survival, growth, and reproduction.

Nutrients are categorized into macronutrients (carbohydrates, fats, proteins) and micronutrients (vitamins and minerals).

Functions of Nutrients

Carbohydrates serve as one of the main energy sources alongside fats; they are crucial for ATP production.

Glycemic index (GI) measures how carbohydrates affect blood glucose levels post-digestion.

Understanding Glycemic Index

Classification of GI

The glycemic index ranges from 0 to 100:

Low GI: 0–55

Moderate GI: 56–69

High GI: 70–100.

Impact on Blood Glucose Levels

High GI foods quickly raise blood glucose levels while low GI foods do so slowly; this affects insulin release significantly.

Role of Carbohydrates in Diet

Fiber's Importance

Indigestible carbohydrates like cellulose help bulk stool and promote gut motility while feeding gut microflora.

Functions of Fats

Energy Source & Structural Role

Fats are another primary energy source used for insulation and structural support around organs.

Cell Membrane Integrity

Cholesterol is included under fats due to its role in maintaining cell membrane integrity and steroid synthesis.

Importance of Proteins

Primary Functions Beyond Energy

Proteins mainly provide structure and function within cells rather than serving as an energy source. They can be broken down into amino acids when needed.

Minerals and Vitamins Overview

Types of Minerals

Minerals can turn into ions in the body; examples include sodium, magnesium, potassium, calcium, with trace minerals like zinc being required in smaller amounts.

Vitamins Classification

Vitamins are divided into water-soluble (not stored in the body) and fat-soluble (stored in body fat).

Essential Nutrients Explained

Necessity from Diet

Essential nutrients must be obtained through diet since the body cannot synthesize them. This includes essential fatty acids, amino acids, vitamins, and minerals.

Essential Nutrients Overview

Essential Amino Acids

There are nine essential amino acids for adults and ten for children or young adults. These include phenylalanine, valine, leucine, isoleucine, threonine, methionine, lysine, histidine, and tryptophan.

Phenylalanine is crucial as it can be converted into tyrosine, which is necessary for producing neurotransmitters like noradrenaline and dopamine.

Essential Fatty Acids

The two essential fatty acids to note are alpha-linolenic acid (omega-3) and linoleic acid (omega-6).

Just like amino acids can lead to the synthesis of other amino acids, these essential fatty acids can also give rise to other types of fatty acids.

Vitamins: Water-Soluble vs. Fat-Soluble

Water-Soluble Vitamins

Water-soluble vitamins must be ingested through diet or supplements since they cannot be synthesized by the body. They act primarily as coenzymes in metabolic processes.

Key water-soluble vitamins include Vitamin C and B-complex vitamins such as B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folic acid), and B12.

Fat-Soluble Vitamins

Fat-soluble vitamins can be stored in the body more easily than water-soluble ones. Overdosing on fat-soluble vitamins is a concern due to their storage capability.

Important fat-soluble vitamins include Vitamin A (carotenoids/retinoids), D (calciferols), E (tocopherols), and K.

Minerals

Trace minerals such as iron, zinc, fluoride are vital; there are 15 trace minerals important for various bodily functions.

Energy Measurement: Calories vs. Kilojoules

Calories measure energy based on how much heat is required to raise the temperature of one gram of water by one degree Celsius.

The calorimetry method involves burning food in a container with water to measure temperature changes that indicate calorie content.

Transition from Calories to Kilojoules

In Australia, kilojoules have replaced calories as the standard unit of energy measurement in food due to metric system usage; 1 calorie equals approximately 4.2 kilojoules.

Vitamin D Overview

Importance of Vitamin D

Vitamin D is a fat-soluble vitamin necessary for normal growth and development; it cannot be produced by the body but must be obtained from external sources.

Synthesis of Vitamin D

The primary source of vitamin D comes from UV exposure or sunlight which initiates its conversion into an active form within the body.

Vitamin D Metabolism and Function

Conversion of Cholesterol to Vitamin D

UV light exposure triggers the conversion of a cholesterol derivative in the skin, known as seven-dehydrocholesterol, into cholecalciferol (vitamin D3) which then enters the bloodstream.

Activation Process in the Liver

Cholecalciferol is transported to the liver where it is converted by an enzyme called 25-hydroxylase into 25-hydroxycholecalciferol (calcifediol), which remains inactive at this stage.

Dietary Sources of Vitamin D

Ingested vitamin D from animal products primarily comes from fish and liver as cholecalciferol, while plant sources like UV-activated mushrooms provide ergocalciferol (vitamin D2). Both forms undergo hydroxylation in the liver.

Final Activation in the Kidneys

Calcifediol travels to the kidneys where it encounters another enzyme, one-alpha hydroxylase, converting it into calcitriol (1,25-dihydroxycholecalciferol), which is the active form of vitamin D. This process requires stimulation for activation.

Importance of Enzymes and Testing

The enzymes involved are crucial for vitamin D metabolism; blood tests typically measure calcifediol levels rather than calcitriol levels, providing insight into baseline vitamin D status. Low calcium or phosphate levels stimulate one-alpha hydroxylase activity leading to increased calcitriol production.

Role of Active Vitamin D (Calcitriol)

Functions of Calcitriol

The primary role of calcitriol is to increase calcium and phosphate levels in the blood when they are low; this involves stimulating absorption and reabsorption processes within various body systems.

Mechanism of Action

Calcitriol increases gastrointestinal absorption and renal reabsorption of calcium and phosphate while also enhancing osteoclast activity to release these minerals from bones into circulation. This process ensures that both minerals are available for bone mineralization later on.

Relationship Between Calcium and Phosphate

Calcium and phosphate work together; their simultaneous presence supports bone health through mineralization processes. Without adequate vitamin D, parathyroid hormone can raise blood calcium but may lead to phosphate loss via urine excretion, disrupting their balance essential for strong bones.

Understanding Vitamin D: Deficiencies and Toxicities

The Importance of Vitamin D

Vitamin D is crucial for bone health; without it, bones can become brittle due to the influence of parathyroid hormone.

Prevalence of Deficiency

Approximately 50% of the global population is vitamin D deficient, primarily due to insufficient sunlight exposure. Skin color affects vitamin D production, with lighter skin producing five times more than darker skin.

Causes of Deficiency

Key causes include lack of UV light exposure and issues with fat absorption since vitamin D is a fat-soluble vitamin that requires fats for proper absorption.

Problems in bile production or intestinal tract function can hinder fat absorption, leading to diminished vitamin D levels.

Recommended Intake Levels

Recommended daily intake varies by age:

400 IU for infants under one year,

600 IU for ages 1 to 70,

800 IU for those over 70 years old.

Health Consequences of Deficiency

Insufficient vitamin D can lead to rickets in children (soft bones due to lack of mineralization) and osteomalacia in adults (brittle bones from calcium depletion).

Vitamin D Toxicity: Risks and Symptoms

Overdosing on Vitamin D

Excessive intake, particularly through supplements rather than sunlight, poses significant health risks as it leads to toxicity.

Symptoms of Toxicity

Classic symptoms include "stones, bones, abdominal moans, and psychic groans":

Stones: Increased calcium levels raise the risk of kidney stones.

Bones: Osteomalacia results from excessive calcium leaching from hardened bones.

Abdominal Moans: High calcium levels cause muscle contractions leading to abdominal pain.

Psychic Groans: Elevated calcium depresses nervous system activity affecting neuron firing.

Overview of Other Fat-Soluble Vitamins

Introduction to Vitamins A, K, and E

Following the discussion on vitamin D, an overview will be provided on vitamins A (retinoids), K, and E.

Understanding Vitamin A Sources

Vitamin A can be obtained from both plant (beta-carotene) and animal sources (retinol). It plays a vital role in various bodily functions.

Metabolism of Vitamin A

Retinol can convert into retinal or retinoic acid within the body. However, once converted into retinoic acid, it cannot revert back.

Storage Characteristics

Being fat-soluble allows vitamin A to be stored effectively in the body; its storage involves complex interactions with long-chain fatty acids.

What is the Role of Retinol in the Body?

Functions of Retinol

Retinol, esterified with palmitate, plays a crucial role in night vision, particularly in low or dim light conditions.

It is essential for maturation and development, maintaining healthy skin and mucosa, and supporting reproductive health in both males (sperm production) and females (healthy placenta during pregnancy).

Mechanism of Action

In retinal cells, retinol converts to 11-cis-retinal which binds to opsin to form rhodopsin.

Rhodopsin reacts to light by stimulating the optic nerve, enabling night vision; without vitamin A, night blindness can occur.

Importance of Vitamin A

Long-term vitamin A deficiency can lead to blindness; approximately 500,000 children globally are affected due to this deficiency.

Fortification efforts like golden rice aim to prevent vitamin A deficiency-related blindness.

Consequences of Vitamin A Imbalance

Health Risks

Both excessive and insufficient vitamin A levels pose risks: too little can cause reproductive issues and skin damage while too much can threaten pregnancy.

Cellular Functionality

Retinol enters body cells where it transforms into retinoic acid that promotes DNA transcription into mRNA for protein synthesis.

These proteins contribute to various functions including tissue maturation, skin health maintenance, and reproductive processes.

Understanding Vitamin K's Role

Coagulation Process

Vitamin K is vital for blood coagulation; it aids platelets in forming a meshwork that stops bleeding after injury.

Protein Synthesis

Within cells, DNA transcribes mRNA for coagulation factors which are then translated into proteins necessary for clotting.

The Carboxylation Process

Activation by Vitamin K

Proteins require carboxylation (addition of carbon dioxide), facilitated by vitamin K. This modification allows them to bind effectively with platelets during coagulation.

Mechanism Overview

The negatively charged coagulation factors enhance platelet binding at injury sites promoting tissue regeneration post-injury.

Understanding the Role of Calcium and Vitamins in Blood Clotting

The Importance of Calcium in Clotting

Calcium is essential for blood clotting as it has two positive charges that facilitate binding with negatively charged platelets and coagulation factors.

Vitamin K activates coagulation factors; without it, these factors can be produced but remain uncarboxylated, impairing their ability to promote clotting.

Blood banks use a chelating agent to bind calcium during blood donation to prevent clotting in storage.

Overview of Vitamin E

Vitamin E, also known as tocopherol or alpha-tocopherol, acts as a potent antioxidant against peroxyl free radicals.

Antioxidants counteract oxidants that pull electrons from molecules, which can destabilize cell membranes rich in fatty acids.

Mechanism of Action for Vitamin E

Peroxidation damages fatty acids by stealing electrons, leading to a chain reaction of free radical production that harms cells.

Vitamin E neutralizes peroxyl free radicals by binding to them; however, this process depletes vitamin E's availability until it is regenerated by vitamin C.

Sources and Deficiency Risks of Vitamin E

Rich sources of vitamin E include nuts, seeds, and liver; deficiency is rare due to its storage capabilities but can occur.

Metabolism: Breakdown and Absorption of Macronutrients

Digestion Process Overview

Ingested macronutrients (proteins, fats, carbohydrates) are broken down into smaller components during digestion in the stomach and intestines.

Nutrient Absorption Pathways

Proteins break down into amino acids; carbohydrates into glucose; triglycerides into glycerol and fatty acids before being absorbed via the portal vein to the liver.

Distinction Between Fatty Acids and Other Nutrients

Unlike proteins and carbohydrates that go directly to the liver via the portal vein, triglycerides enter systemic circulation through the lymphatic system.

Storage and Energy Production from Nutrients

Storage Mechanisms Post-Digestion

After absorption, nutrients are stored: amino acids as proteins, glucose as glycogen (inactive), glycerol and fatty acids as triglycerides (fat).

Energy Production Pathway

Glucose is converted into pyruvate then enters mitochondria where it's transformed into acetyl-CoA for energy production through the Krebs cycle.

Byproducts of Energy Metabolism

The Krebs cycle generates ATP while releasing carbon dioxide; hydrogen produced during this process interacts with mitochondrial membrane proteins alongside oxygen.

Metabolic Processes and Glycogenesis

Oxidative Phosphorylation and ATP Production

Oxygen interacts with transmembrane proteins to produce ATP through oxidative phosphorylation, primarily via the electron transport chain, generating approximately 30 to 36 ATP molecules.

Anaerobic Conditions and Lactic Acid Formation

During high-intensity activities like sprinting, oxygen becomes a limiting factor for ATP production. This leads to a backlog in the process, resulting in pyruvate converting into lactic acid, which can still generate ATP without oxygen.

Fatty Acids and Energy Metabolism

Triglycerides are broken down into glycerol and fatty acids; glycerol can enter glucose metabolism at the pyruvate level while fatty acids enter at acetyl CoA. Once past pyruvate, conversion back to glucose is not possible.

Ketone Production from Excess Acetyl CoA

In the absence of glucose, triglycerides are utilized for energy. However, excess acetyl CoA can lead to ketone production (e.g., beta-hydroxybutyrate), which can also be converted into ATP.

Overview of Glycogenesis

The video transitions to glycogenesis—defined as the formation of glycogen from glucose. Glycogen serves as a stored form of glucose that efficiently produces energy (34-36 ATP per molecule).

Storing Glucose as Glycogen

Glycogenesis occurs during fed states (0-4 hours post-meal), where ingested glucose is converted into glycogen for storage in liver or muscle tissues.

Conversion of Glucose to Glucose 6-Phosphate

The first step in glycogenesis involves converting glucose into glucose 6-phosphate using ATP. This compound is crucial for both glycolysis and glycogen synthesis.

Role of Phosphoglucomutase

An enzyme called phosphoglucomutase relocates the phosphate group on glucose 6-phosphate from the sixth carbon to the first carbon position, preparing it for further processing.

Uridine Triphosphate's Functionality

Uridine triphosphate (UTP), a nucleotide similar to ATP but containing uracil instead of adenine, plays a role in attaching phosphates during glycogen synthesis by forming uridine diphosphate (UDP).

Enzymatic Action in Glycogen Synthesis

The enzyme glycogen synthase facilitates linking together glucose molecules by removing UDP and connecting them at specific carbon positions (first and fourth carbons), creating branched structures within glycogen.

Glycogen Structure and Function

Glycogen Binding Types

Glycogen is formed through one-to-four and one-to-six binding, resulting in a branched structure that serves as glucose storage in animals.

Comparison with Plant Storage

Animals store glucose as glycogen, while plants store it as starch and cellulose. Starch has a similar structure to glycogen but is less branched.

Cellulose Structure

In cellulose, every second glucose unit is inverted, complicating digestion for some organisms. This structural difference affects enzyme action on cellulose compared to glycogen.

Digestibility of Carbohydrates

Humans lack the enzymes to break down the flipped bonds in cellulose, making it indigestible fiber. Cows can digest cellulose due to specific enzymes.

Understanding Gluconeogenesis

Definition of Gluconeogenesis

Gluconeogenesis refers to the production of new glucose from non-carbohydrate sources like proteins and fats.

Importance of Glucose Production

The brain primarily relies on glucose for energy; thus, gluconeogenesis becomes crucial during fasting or low blood sugar states.

Hormonal Regulation

Low blood glucose triggers the pancreas to release glucagon, cortisol, and noradrenaline—hormones that stimulate gluconeogenesis.

Pathway of Lactate Conversion

Lactate's Role in Gluconeogenesis

Lactate produced by muscles can be converted back into pyruvate within liver cells (hepatocytes), which is essential for gluconeogenesis.

Steps from Pyruvate to Glucose

Pyruvate cannot revert directly back into glucose; instead, it undergoes several steps involving oxaloacetate before ultimately forming glucose again.

Krebs Cycle Connection

Oxaloacetate plays a critical role in linking acetyl CoA with the Krebs cycle for ATP production while also being involved in gluconeogenesis processes.

Gluconeogenesis and Its Role in Blood Glucose Regulation

The Process of Gluconeogenesis

Fructose 1,6-bisphosphate cannot revert to glucose 6-phosphate without the enzyme fructose 1,6-bisphosphatase, which facilitates this conversion.

Once converted to glucose 6-phosphate, it is transformed into glucose by the enzyme glucose 6-phosphatase in the smooth endoplasmic reticulum, leading to increased blood glucose levels.

Lactate from muscles enters gluconeogenesis as pyruvate, converting through various intermediates until reaching fructose 1,6-bisphosphate.

Glycerol from triglycerides also participates in gluconeogenesis similarly to lactate, ultimately producing glucose when needed.

Fatty acids enter mitochondria and convert into acetyl-CoA; however, they cannot directly form glucose.

Amino Acids and Their Contribution

Certain amino acids like alanine and glutamate can enter gluconeogenesis at different stages, contributing to glucose production.

Proteins are broken down into amino acids that can be utilized for energy or converted back into glucose.

Impact of Diabetes on Metabolism

In diabetic individuals with low insulin levels, triglyceride breakdown occurs repeatedly due to insufficient glucose availability.

Excess acetyl-CoA accumulates because oxaloacetate is diverted for gluconeogenesis instead of binding with acetyl-CoA for energy production.

This accumulation leads to ketone production (beta-hydroxybutyrate and acetoacetate), which can provide energy but may also result in ketoacidosis if insulin is absent.

Hormonal Regulation of Gluconeogenesis

Key triggers for gluconeogenesis include low blood glucose levels; hormones such as glucagon, cortisol, and noradrenaline play significant roles alongside substrates like lactate and glycerol.

Understanding the Fed State: Metabolic Changes After Eating

Characteristics of the Fed State

The fed state follows meal consumption characterized by high blood glucose levels leading to elevated insulin secretion from pancreatic beta cells.

Breakdown of Macronutrients

After eating a meal containing proteins, fats, and carbohydrates (macronutrients), these are digested primarily in the mouth and small intestine into their basic components: glucose, fatty acids, glycerol, and amino acids.

Absorption Mechanisms

Fatty acids and glycerol from triglycerides are absorbed via the lymphatic system after digestion.

Insulin's Role Post Meal

High blood sugar prompts insulin release which decreases blood sugar by facilitating cellular uptake of glucose while inhibiting lipolysis (fat breakdown).

Effects on Protein Metabolism

Insulin also inhibits proteolysis (protein breakdown), promoting an anabolic state where nutrients are stored rather than used for immediate energy.

Understanding Insulin and Glucose Metabolism

The Role of Insulin in Energy Production

Insulin primarily promotes the storage of nutrients after eating, helping to lower blood glucose levels by facilitating glucose entry into cells.

Certain tissues, like muscle and fat, are insulin-dependent for glucose uptake, while others (liver, brain, kidneys) can absorb glucose independently of insulin.

Glucose Processing in the Liver

In the liver, glucose is always absorbed regardless of insulin presence; it is primarily stored as glycogen (inactive form).

Glycogen acts like "Lego blocks," representing how glucose is stored. Less than 10% may convert to pyruvate through glycolysis.

Pyruvate can transform into acetyl-CoA, which enters the Krebs cycle to produce ATP (energy), or be used to synthesize fatty acids and glycerol.

Fat Storage Mechanisms

Acetyl-CoA can lead to triglyceride formation when combined with glycerol; these triglycerides are transported via very low-density lipoproteins (VLDL).

Amino acids from food also enter the liver and can directly participate in energy production through the Krebs cycle.

Muscle Tissue's Response to Insulin

Muscle tissue requires insulin for glucose uptake; once inside, glucose can be stored as glycogen or converted into pyruvate for energy production.

Amino acids entering muscle tissue are predominantly stored as proteins alongside glycogen.

Adipose Tissue Functionality

Like muscle tissue, adipose tissue needs insulin for glucose entry but does not store it as glycogen; instead, it undergoes glycolysis leading to fatty acid synthesis.

Fatty acids and glycerol absorbed from meals form chylomicrons that deliver these substances to adipose tissue for triglyceride storage.

Post-Absortive State: Fasting Metabolism

Importance of Glucose Regulation

The post-abortive state features decreased blood glucose levels; understanding this state is crucial since organs like the brain rely heavily on carbohydrates for energy.

Normal Blood Glucose Levels

Normal blood glucose levels range between 4 to 6 millimoles per liter. Maintaining this balance is essential—levels too low require elevation while high levels necessitate reduction.

What Happens After Extended Periods of Fasting?

Understanding the Post Absorptive State

The discussion focuses on the physiological processes that occur during fasting, specifically in the post absorptive state, which can last from four to eight hours or longer, such as overnight fasting for 10 to 12 hours.

The speaker introduces key organs involved in maintaining blood glucose levels: the liver (hepatocytes), pancreas, muscle tissue, and adipose tissue.

A 70 kg male has approximately 80 grams of glycogen stored in his liver. Glycogen is a stored form of glucose used when energy is needed.

Glycogen Breakdown and Blood Glucose Regulation

During fasting, glycogen breaks down into glucose 6-phosphate through enzymatic action. This process allows glucose to be released into the bloodstream to maintain blood sugar levels.

The pancreas plays a crucial role; when blood glucose levels drop, alpha cells produce glucagon, stimulating glycogen breakdown into glucose.

As blood glucose increases due to glycogenolysis (the breakdown of glycogen), it triggers beta cells in the pancreas to release insulin, which helps lower blood sugar levels by inhibiting further glycogen breakdown.

Maintaining Blood Glucose Levels Over Time

Insulin acts as a negative regulator while glucagon serves as a positive regulator. This balance ensures stable blood glucose levels during fasting periods.

The process discussed is termed glycogenolysis—breaking down glycogen into glucose for energy production. However, with only 80 grams available, this source depletes after prolonged fasting.

Transitioning to Gluconeogenesis

Once glycogen stores are exhausted after about 10–12 hours without food intake, gluconeogenesis becomes essential for maintaining blood glucose levels.

Glucagon stimulates gluconeogenesis by promoting proteolysis in muscles and fat breakdown into fatty acids and glycerol. This process relies on low insulin levels for activation.

Amino acids derived from protein breakdown contribute to gluconeogenesis; alanine is highlighted as an important amino acid in this metabolic pathway.

Metabolic Pathways and Gluconeogenesis

Overview of Metabolic Processes

The body utilizes glycogen stores when insulin levels are low, leading to high glucagon levels and stimulating proteolysis, releasing amino acids like alanine.

Glycerol from triglycerides can be converted into glucose through glycolysis, which is the process of converting glucose into ATP.

The Krebs cycle (citric acid cycle) produces NADH and carbon dioxide, with NADH entering the electron transport chain for ATP production.

Role of Glycerol and Alanine in Gluconeogenesis

Glycerol can enter the glycolytic pathway reversibly to increase blood glucose levels by converting to glucose 6-phosphate.

Alanine converts to pyruvate; although pyruvate cannot revert directly to glucose 6-phosphate, it can transform into oxaloacetate, which eventually contributes to gluconeogenesis.

Impact of Fatty Acids on Metabolism

Fatty acids convert into acetyl CoA but may lead to a decrease in oxaloacetate due to their conversion processes, creating an imbalance in metabolic pathways.

An excess of acetyl CoA results in its conversion into ketones when there is insufficient oxaloacetate available for binding.

Utilization of Lactate and Other Substrates

Lactate can also serve as a substrate by converting back into pyruvate, contributing further to gluconeogenesis alongside other non-carbohydrate sources like glycerol and fatty acids.

Hormonal Regulation of Gluconeogenesis

Insulin negatively regulates gluconeogenesis; after prolonged fasting (10–12 hours), it accounts for about 50% of blood glucose release as glycogen stores deplete.

Besides glucagon, hormones such as noradrenaline, adrenaline, cortisol, growth hormone, and thyroid hormones stimulate gluconeogenesis. Adrenaline acts quickly while others have slower effects.