What a Set of Batteries!

A COMMENTARY ON THE ORIGIN AND USE
OF OUR BODY'S ENERGY.

by Walter Bortz, MD - from Diabetes Wellness Letter

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Have you ever pondered such intricacies of life as where am I going to get the energy to climb another flight of stairs, walk another mile, teach another class or meet another client?

Quite often, we rely on a carbohydrate snack to give us an energy boost.

But just where is the energy in that apple, bagel, or piece of candy? How did it get there and how does it get transferred to me?

The answer to these questions lies in a series of chemical reactions that are so logical and beautiful that they seem like miracles. Very simply put, the energy of all living things is derived from the sun. The process of photosynthesis provides the mechanism by which light energy from the sun is transformed into the chemical energy that drives living organisms.

The leaves of plants are equipped with special structures called photocenters that function as light-capturing antennae. It is a-highly organized arrangement of chlorophyll pigments within these antennae that allows the absorption and transformation of sun rays into the chemical energy needed to make glucose or chains of glucose called starch. With ample supplies of energy plant cells take simple inorganic raw materials — carbon dioxide (CO2) and water (H2O) — breaks them up and reshuffles their atoms into a different arrangement that is held together by chemical bonds. The end result is glucose in sugar cane and starch in plants like fruits, vegetables and grains.

Thus, the basic chemical equation we all learned in high school: Six molecules of carbon dioxide plus six molecules of water in the presence of sunlight yields one molecule of glucose.

6 CO2 + 6 H2O + light energy =======> C6 H12 O6 + 6 O2.

An additional benefit of this process is that oxygen is formed as a by–product.

This chemical equation, however, reflects only the beginning and end of a complex process involving hundreds of chemical reactions, each of which depends on the orderly execution of all of the preceding reactions.

So much for plants. How do human beings, lacking as they are in leaves and chlorophyll, harvest energy from the sun?

Of course the obvious answer is by partaking of foods created through the above process.

What may not be so obvious is that our bodies are designed with complicated networks of diverse molecules, cells, tissues, organs and organ systems that collectively enable every one of our billions of cells to obtain the energy needed to sustain themselves and carry out their individual functions.

Our digestive and nervous systems facilitate the ingestion of food and contribute the enzymes that break down sugars and starches into glucose. The endocrine system contributes insulin which, along with glucose, is delivered to cell membranes via the circulatory system.

Once it is inside the cell some glucose gets converted to glycogen — a storage form of glucose — that acts as an energy reservoir. The rest is delivered to the batteries of the cell called mitochondria. Each microscopic mitochondrion contains hundreds of enzymes with highly specific tasks. As each enzyme does its work, a chemical reaction causes breaks in the chemical bonds of the glucose molecule producing a different glucose derivative until the original molecule has been fully degraded to the components from which it arose in the plant — carbon dioxide and water.

Whenever chemical bonds are broken, energy is released. The energy released as mitochondrial enzymes break up the chemical bonds in the glucose molecule that is used by the cell for two purposes.

The first purpose is to do the primary business of that particular cell, whether it be movement, nerve conduction, hormone production or whatever.

The second purpose is to nourish the genetic machinery of the cell (DNA), to keep its structure and function intact.

Whenever this whole process is dissected into its tiny details, it seems tedious and mechanical. But when you stop to think that a redwood, a whale and you and I are interconnected by virtue of our dependence on sunbeams it seems to be a miracle. We are all the sun's children, with plants serving as abundant, efficient intermediaries that sustain our life.


Walter M. Bortz II, MD is a member of the teaching faculty at Stanford University Medical School and a practicing physician at the Palo Alto Medical Foundation. He is the author of numerous scientific articles and two books:  We Live Too Short and Die Too Long and the recently released Dare to be 100. He is past president of the American Geriatric Society and former co-chair of the AMA-ANA Task Force on Aging. He is also a marathon runner.
Simply Science

In response to many requests from our membership for a better understanding of what diabetes is and the scientific basis for its treatment, the editors and authors of Diabetes Wellness Letter will be including more references to, and explanations of, the cellular processes related to the various topics addressed in this publication. We begin with this issue and the following description of a generic human cell.

The cell is the fundamental unit of life, the smallest structure in the body of which various tissues and organs are made. Although most cells are invisible, they are 3 dimensional, with varying sizes and structures depending on the tissue or organ they serve.

Human cells contain smaller substructures called organelles ("Little organs"), each of which performs a different task related to the purpose and function of the cell. The organelles depicted in the cell diagram on page 2 are the ones that are common to all human cells. Some human cells have additional structures depending on what purpose they serve.

An understanding of how normal cells work facilitates the understand, of how abnormalities in cell function cause diseases like diabetes. An understanding of cellular structure and function also facilitates an understanding of how recommended treatments, including medications, achieve their intended results.

Cell Membrane — A thin, non rigid structure made of protein and lipids that encloses cell contents and regulates interactions between the cell and its external environment. Nothing can enter or leave the cell without passing through this membrane.

Nucleus — As the cell's command center, it contains genetic material (DNA) that is bound to proteins in chromosomes. A double membrane encloses the nucleus but pores in this membrane allow various kinds of molecules to move in and out of the nucleus.

Mitochondrion — Sausage shaped organelles that are the power sources for the cell. They are bounded by two membranes. The outer membrane is smooth and defines the shape. The inner membrane contains many folds called cristae that extend into the interior mitochondrion. Cristae are lined with the enzymes needed to break down glucose and fatty acids. The energy released during this breakdown is stored in the mitochondrion and released as needed for the work of the cell.

Cytoplasm — A gel-like fluid located between the cell membrane and the nucleus. It is 75% water and 25% protein. The proteins, mostly in the form of enzymes or structural filaments, make the cytoplasm viscous.

Endoplasmic Reticulum (ER) — An extensive "net" of interconnected, flat membranes that form a system of channels and tubes moving substances from one part of the cell to another.

There are two types of ER: Rough ER and Smooth ER.

Rough ER has spherical structures called ribosomes dotting its surfaces giving it the rough appearance. Ribosomes begin the process of building specific proteins, most of which eventually leave the cell to perform a function somewhere else in the body. When ribosomes have finished their assigned task they pass the protein along to the inner channels of the ER where enzymes make further modifications to complete the manufacturing process.

Smooth ER has no ribosomes so it does not make proteins. Instead smooth ER contains enzymes which build carbohydrate and lipids.

Golgi body — Flattened sets of membranes that function as a refining and packaging station for manufactured proteins destined for export to other cells. The protein products are encased in membranous sacs called secretary vesicles. Eventually these sacs will move out of the golgi body, migrate to the interior surface of the cell membrane and be forced out into the blood.

Lysosomes — Vesicles that contain digestive enzymes used to break down old cell parts or materials brought into the cell from the environment such as bacteria. You could call them the cell's junkyard or recycling station. What can be reused or rebuilt is saved while true trash is destroyed by enzymes within the lysosome.


Table 1  

The Amino Acids
From Which All Proteins Are Made
Beta–Alanine NH2CH2CH2CO2H 13 Atoms
DL–Alanine CH2CH(NH2)COOH 12 Atoms
L–Alanine CH2CH(NH2)COOH 12 Atoms
Arginine C6H14N4O2 26 Atoms
Asparagine NH2COCH2CH(NH2)COOH 17 Atoms
Aspartic Acid HOOCCH2CH(NH2)COOH 16 Atoms
Cysteine HSCH2CH(NH2)COOH 14 Atoms
Glutamic Acid HO2CCH2CH2CH(NH2)CO2H 19 Atoms
Glutamine
Atoms
Glycine NH2CH2COOH 9 Atoms
Histadine
Atoms
Isoleucine CH3CH2CH(CH3)CH(NH2)COOH 22 Atoms
Leucine (CH3)2CHCH2CH(NH2)COOH 22 Atoms
Lysine NH2(CH2)4CH(NH2)COOH 24 Atoms
Methionine CH3SCH2CH2CH(NH2)COOH 20 Atoms
Phenylalanine C6H5CH2CH(NH2)CO2H 23 Atoms
Proline C5H9NO2 17 Atoms
Serine HOCH2CH(NH2)COOH 14 Atoms
Threonine CH3CH(OH)CH(NH2COOH 17 Atoms
Tryptophan C11H12N2O2 27 Atoms
Tyrosine HOC6H4CH2CH(NH2COOH 24 Atoms
Valine (CH3)2CHCH(NH2)COOH 19 Atoms

It takes more than just Amino Acids, to make Proteins.

 
 

  

CELEBRATING INSULIN: 1921-1996

The Inside Story on the Production and Structure of this
Life–Sustaining Hormone.


Over the past 75 years, much has been learned about the miraculous substance that Banting and Best dubbed the "internal secretion of the pancreas".

We now know that the pancreas consists of several different types of cells that produce several different substances required for the digestion and proper utilization of food. Some of these substances are enzymes and some are hormones but each has a specific task. Insulin is a hormone and in order to understand how its production and structure relate to its function in human bodies, it is helpful to know a little about hormones in general.

Hormones act as chemical messengers. They are manufactured by specialized cells in various tissues, usually glands and then exported to other cells in the body whose particular function requires their presence. Within the endocrine system, there are over 10 different glands that make over 30 different hormones.

Endocrine hormones fall into 2 categories: peptide hormones and steroid hormones.

Insulin is a peptide hormone meaning that it is a protein compound made up of more than one chain of amino acids. Amino acids are the building blocks of body proteins and it is the number, type and sequence of specific amino acids that determine the individual structure and function of thousands of different proteins in all living organisms. Table 1 lists the 20 amino acids from which all protein is made and Figure 1 shows the amino acid sequence of the insulin molecule in two different stages of formation: A) in its storage form called proinsulin and B) its active form that travels to target cells.


HOW AND WHERE IS INSULIN MADE?

Scattered throughout the pancreas are clusters of specialized cells called islets of Langerhans. The human pancreas contains 12 million islets. One type of cell within these islets is called the beta cell and it has been programmed to make, store and secrete insulin in the precise amounts needed to keep blood glucose levels between 65 and 115. The production process is described below but as you read you may find it helpful to refer back to the diagram of a cell and locate the various cell organelles involved in making insulin.

Production of insulin occurs in stages and begins in the ribosomes on the rough endoplasmic reticulum of beta cells. These ribosomes have received the recipe and instructions for making insulin from DNA located in the nucleus of the cell.

After the ribosomes have constructed a "rough model" of the insulin protein, it is moved to the interior channels of the endoplasmic reticulim where enzymes further modify the molecule separating it into two peptide chains (the A chain and the B chain) that are connected by a third peptide chain called the connecting peptide, also known as C-peptide. (see Fig. 1A)

This is the storage form of insulin called proinsulin. Proinsulin is then moved into a golgi body where it is folded in such a way that causes chemical bonds to form between some of the amino acids that become close neighbors as a result of the folding patterns. Proinsulin is then packaged and stored in membranous sacs called secretary vesicles.

Immediately prior to secretion, the microscopic insulin sacs are moved out of the golgi body and up to the cell membrane. Enzymes detach the connecting peptide chain from the A and B chains creating two separate molecules: C–peptide and the active form of insulin. (See figure 1B)

The membrane of the insulin sac fuses with the cell membrane. Both insulin and C–peptide are then pushed out of the cell into the blood.

C–peptide has no other known function but since it is secreted in amounts equal to insulin it has become an indicator of how well beta cells are functioning. If there is no C–peptide present in blood, there is no insulin being secreted.


Celebrating Insulin

1921 – l996

The normal pancreas beta cell, through complex chemical and electrical mechanisms, has the ability to rapidly sense glucose levels in the blood and secrete insulin in the precise amounts needed to keep the concentration of glucose from rising above 115 mg / deciliter. Insulin also plays a role in the metabolism of protein and fat.

Once released into the bloodstream, insulin travels to its "target cells" where it must find and dock onto protein structures on the cell membrane called receptors. The protein structure of the cell's insulin receptor is designed so that it can only attract and bind to the insulin protein molecule. Thus, insulin has its own "landing pads" on its target cells which are primarily liver, muscle and fat cells

INSULIN ACTION IN MUSCLE AND FAT CELLS

When insulin docks on to muscle and fat cell receptors it triggers numerous reactions inside these cells which enable it to take in glucose and use it as fuel. The process is depicted above in figure 1. The basic sequence is as follows:

1. Insulin finds and docks onto its receptor.

2. A signal is sent to a pool of glucose transport proteins (Glut 4 Protein) located inside the cell.

3. These Glut 4 proteins move rapidly up to the cell membrane and cause glucose channels to open.

4. Glucose is "escorted " to the interior of the cell where enzymes will begin to break it down to fuel the work of the cell.

Overall Effects of Insulin on Muscle and Fat

IN MUSCLE

Increased rate of glucose transport into muscle by Glut 4 carriers. Result: Reduction of blood glucose levels and increased availability of energy for muscle contraction.

Conversion of glucose into glycogen is increased. The glucose that isn't needed immediately for energy to power muscle contraction will be stored as glycogen. The key enzyme that speeds this process is glycogen synthase.

Increased entry of amino acids from the blood. Amino acids are the building blocks of protein. Once inside the muscle most of them are sent to ribosomes where the manufacture of various muscle protein will take place.

Overall Effects of Insulin on Muscle and Fat

Decreased breakdown of existing muscle proteins into glucose. This effect of insulin along with each of the above is essential to the muscle's ability to grow and maintain itself.

What is the effect of diabetes on the above?

Insufficient insulin causes the reverse of all of the above. The severity of the reversal is proportional to the severity of the insulin deficiency. Glucose cannot be delivered to muscle cells so they lack quick fuel to do their work. Muscle cells then begin to convert glycogen stores to glucose but there is no new glycogen being formed. When glycogen stores get too low muscle cells turn to fat and protein as fuel sources but new amino acids cannot get into cells to replace the protein losses. The result is elevated blood glucose, loss of muscle mass, weight loss, weakness and fatigue.

IN FAT

When insulin docks onto fat cells it triggers reactions that allow the efficient storage of both excess blood glucose and blood fats inside the fat cell.

Increased entry of glucose into fat cells is removed from the Conversion of the excess glucose into storage forms of fat (fatty acids). This provides the body with an energy reserve that can be utilized during prolonged exercise or fasting.

Depositing of blood fats (triglycerides) into fat cells is increased. What is the effect of diabetes on the above?

Again insulin deficiency prevents the above and the severity of the deficiency correlates to the severity of the metabolic consequences. Glucose cannot get in to the fat cell to be converted to fat. This contributes to the elevated blood glucose. Fat is then broken down for energy but it is a slower process than that which converts glucose to energy. This breakdown of fat as the only source of energy produces ketoacidosis in persons with Type I diabetes and gestational diabetes. Serious biochemical abnormalities occur in type II diabetes. Fats build up in the blood and contribute to the vascular changes that underlie all of the diabetic complications.


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