METABOLISM OF CARBOHYDRATE, PROTEIN AND LIPIDS

Metabolism is derived from the Greek word for “change” it represents the sum of the chemical changes that convert nutrients the “raw material” necessary to nourish living organisms into energy and the chemically complex finished products of cells (Garrette et al. 2005).

            Metabolism consist of literally hundred of enzymatic reactions organized into discrete pathways, these pathways proceed in a stepwise fashion transforming substance into end products through many specific chemical intermediates (Garrette et al, 2005).

            Nutrients of Human metabolism, Carbohydrate, lipids and proteins are the major constituents of foods and serve as fuel molecules for the human body. The digestion of these nutrients in the alimentary tract and the subsequent absorption of the digestive end products make it possible for tissues and cells to transform the potential chemical energy of food into useful work (Andrea et al, 2010).

The major absorbed end product of food digestion are monosaccharide mainly glucose (from carbohydrate) monoacyglycerol and long chain fatty acids (from lipid) and small peptides and amino acids (from protein). Once in the blood stream, different cell can metabolize these nutrients (Andrea et al, 2010).

CARBOHYDRATE METABOLISM

After meal, carbohydrates are stored mainly in the liver and in the skeletal muscles as polymers of glucose known as glycogen. The glycogen store in muscle is used by contracting muscles and cannot be converted to glucose because of the absence in muscles the enzyme glucose-6-phosphatase which converts glucose-6-phosphate to glucose (Ezeilo, 2002). On the other hand, the glycogen store in the liver serves for the maintenance of blood glucose concentration in between meals for use by other tissues (Ezeilo, 2002).

The conversion of glucose to glycogen or the synthesis of glycogen is known as glucogenesis while the break down of glycogen to glucose (in the liver) or lactate and pyruvate (in muscles) is known as glycogenolysis (Ezeilo, 2002).

Anaerobic glycolysis in the cytoplasm

The process for the catabolism of glucose begin in the cell cytoplasm with an anaerobic phase called glycolysis in which the glucose molecule is split into 2 equal halves of 3-carbon chains which are converted to acids (Pyruvic or lactic). This is the embden-mejerhof pathway for glycolysis and it generates a net energy of 2ATP molecules per molecule of glucose (Ezeilo, 2002).

            Grafted into the EMP glycolysis, is another cytoplasmic pathway for glycolysis known as the pentose phosphate pathway which occurs in many tissues, but not in skeletal muscles. This pathway oxidizes the carbonation in glucose one at a time, producing the reducing agent known as NADPH required for the synthesis of fats and steroids as well as essential intermediates for synthesis of nucleotides (Ezeilo, 2002). 

Oxidative phosphorylation in the mitochondria

In the presence of oxygen, lactic acid is not formed instead pyruvic acid enters mitochondria where it is completely oxidized to carbon dioxide (Co₂) and water (H₂O). The process in the mitochondria leading to this complete breakdown of pyruvic acid constitute the Kreb’s cycle (citric acid cycle) and the H⁺ released during the oxidation is passed through the flavoprotein-cytochrome respiratory chain cycle to combine with oxygen to form water (Ezeilo, 2002).

            The passage of H⁺ through the respiratory chain is coupled with the phosphorylation of ADP to ATP. From the citric acid cycle, 36 molecules of ATP are additionally released from the full oxidation of pyruvic acid, which brings to a total of 38ATP molecules from one glucose molecules when glucose is broken down in the presence of oxygen (Ezeilo, 2002).

Transport of glucose into cells

Three mechanisms by which glucose enters the cells:

1)        Secondary Active transport: In the small intestines and in the nephrone, glucose transport is linked to the facilitated diffusion of sodium by a symport carrier protein known as SGLT1. The transport derives energy from a primary active transport of sodium on the basal and basolateral membrane hence it is also known as secondary active transport (Ezeilo, 2002).

2)        Simple Diffusion: In the liver, which receives all the glucose absorbed from the gut, the cells are freely permeable to glucose and entry is by simple diffusion (Ezeilo, 2002).

3)        Facilitated Diffusion: Glucose uptake in skeletal muscle, cardiac muscle, adipose tissue, brain, placenta, red blood cell and to some extent in the kidney and small intestines occurs by (Uniport carrier) facilitated diffusion. The glucose transported for facilitated diffusion in their locations are designated as GLUT1 through GLUT4 which are quite distinct from sodium cotransporter. GLUT1 is found in all cells, GLUT2 in liver, pancreatic β-cell, intestine and kidney, GLUT3 in the brain and GLUT4 in the insulin sensitive transporter in muscles and adipose tissues (Ezeilo, 2002).

FAT METABOLISM

The triglycerides is a lipid found in plants and animals and there are major energy reserve and the principal natural derivative of glycerol found in animals (Ramlingan, 2001).

            The triglycerides derived from intestinal absorption of fat are contained in complexes known as chylomicrons, together with triacylglycerol  synthesized by the liver are transported in the blood as very low density lipoprotein (VLDL, rich in lipid (Ezeilo, 2002). They must be hydrolyzed into fatty acids and glycerol before they can be catabolized. The hydrolysis of these triacylglycerol occurs intervascularly by the action of vascular lipoprotein lipase located in the capillary endothelium of various organs (heart, adipose tissue, lungs) (Ezeilo, 2002).

            The free fatty acids are transported by albumin and metabolized as fuel extensively by the heart, but practically all tissues can also oxidize them to co₂ and H₂0, in adipose tissue, fatty acids may be stored in fat cell as triacylglcerides, the triacylglycerides, are broken down into fatty acids (FA) and glycerol (Ezeilo, 2002). The enzyme for intracellular hydrolysis of triacylyglycerides is the CAMP-dependent kinase regulated lipase known as the hormone sensitive lipase (Ezeilo 2002).

Oxidation of fatty acids

The first step in the oxidation of fatty acid is the activation of the fatty acid by a combination with co enzymes A (catalyzed by acyl. COA. Synthetase, with energy from ATP) to from fatty acid COA. The activated fatty acid enters the mitochondria, and in the case of long chain fatty acid which cannot enter readily, they combine with a transporter substance known as carnitine which ferries them across (Ezeilo, 2002). The oxidation of the activated fatty acid within the mitochondria occurs at the β – carbon hence it is called a β- oxidation, and leads to the production of β – keto fatty acid COA (Ezeilo, 2002).

            Next is the process of thiolysis in which terminal 2 carbon units are cleaved off by the action of a β – keto thiolase utilizing further COA. The 2- carbon units remain attached to COA and are known as acetylCOA, which is oxidized on the citric acid cycle to CO₂ and H₂O. The total energy yield from complete oxidation of fatty acids is 9kcal/g compared with 4kcal/g for carbohydrate or protein (Ezeilo, 2002).

PROTEIN METABOLISM

Unlike carbohydrate and fats which serves principally to provide energy and are stored in cells, proteins serve principally to provide amino acids which are used to build and maintain tissues (one half of the dry weight of the body protein); from enzymes, hormones, anti- bodies and provide some amount of energy (Ezeilo, 2002). There are no special stores of proteins, instead tissue proteins are being constantly synthesized and degraded and the amino acid pools in the blood and tissue derived from amino acids from the gut or from breakdown of tissue proteins more rapidly than others example the liver, intestinal mucosa and blood. Although, the proteins turnover rate in skeletal muscle is relatively low, the overall effect is large because of its large size (Ezeilo, 2002).

            In general, amino acids in excess of the requirements for the formulation of structural proteins, enzymes, hormones etc are deaminated in the liver to form different amino acids. The ammonia is converted to urea, while the keto acids are eventually oxidized to Co₂ and H₂o with a release of energy which is stored as ATP. Adequate supplies of carbohydrate and fat spare the utilization of protein for energy, but during fasting as the glycogen store is used up, energy is derived from fat and proteins with fat supplying about 85%. When the fat reserves are exhausted, and energy supply depends on protein alone, the large increase in tissue destruction leads rapidly to death (Ezeilo, 2002).

PHYSIOLOGY OF THE WHITE BLOOD CELL

  White blood cells are colourless transparent cells which unlike other blood cell contain nuclei (Ezeilo, 2002). They are cells of the immune system involved in defending the body against both infectious diseases and foreign material (Leafeur, 2008).

            There are 5 different types of leucocytes, but they are all produced and derived from a multipotent cell in the bone marrow as a hematopiotic stem cell. The normal count of white blood cell is somewhere between 4,000 and 10,000/mm³. They have a short lifespan ranging from a few days to a few weeks. These cells offer defensive properties to blood in order to fight against infections and the invading foreign bodies such as bacteria and viruses (Reshman, 2011). If the white blood cell is below normal, it is known as “leucopenia” while if the number of leucocytes increases to more than the normal count, the condition is known as “Leucocytosis”. There may be a decrease in individual leucocyte percentage eg Neutropenia (decrease in neutrophil). The reduction of all types of white blood cell is known as “Panleukopenia” (Reshman, 2011 and Maton et al 2008).

CLASSIFICATION OF LEUCOCYTES

1)        Morphological Grouping.

2)        Functional Grouping.

Morphological grouping: Morphologically, white blood cells are classified into granulocyte and Agranulocytes based on the presence and absence of granules (Ezeilo, 2002).

1)        Granulocytes are leucocytes which have granules in their cytoplasm namely neutrophil, basophil and eosinophil. The individual name is derived from the color of the granules when stained with Ramanowsky stains which contains a basic dye (methylene blue) and an acid like stain (eosin) (Ezeilo, 2002). The granulocyte have segmented nuclei, hence they are called poly morphonuclear leucocytes (Gartner et al, 2007)

2)        Agranulocytes : Are leucocytes characterized by the apparent absence of granules  in their cytoplasm. Though they lack granules, these cells do contain non – specific azurophilic granules which are lysosome (Gartner et al. 2007). The cells include lymphocyte, monocytes and macrophages, they are also called mononuclear leucocytes (Gartner et al. 2007).

Functional classification

Leucocytes are mainly grouped into phagocytes and lymphocytes (Ezeilo, 2002). Phagocytes destroy foreign bodies by engulfing and digesting them within the cell (phagocytosis). These group include all leucocytes except lymphocytes. Lymphocytes destroy foreign bodies by secreting antibodies against them or by directly killing or neutralizing them (Ezeilo, 2002).

Neutrophils

   Neutrophils defend the body against bacterial or fungal infection and other very small inflammatory process that are usually first responders to microbial infection (Gartner et al. 2002). They are the most common cell type seen in the early stages of acute inflammation, and make up 60 – 90% of the total leucocyte count in human blood (Alberts, 2005).

            Mature neutrophils are characterized by multiple segmentation of the nucleus, beginning with 3 lobes joined by chromatin strand and increasing to 5 lobes as the neutrophil gets older. The cell is 10 – 15cm in diameter (Ezeilo, 2002) with lifespan of about 4 – 5 days (Pillay et al, 2010).

Eosinophils

Eosinophils primarily deal with parasitic infections. Eosinophils are also the predominant inflammatory cells in allergic reactions. The most important causes of eosinophilia include allergies such as asthma, hay fever and hives and also parasitic infection. Their nucleus is bilobed and their cytoplasm is full of granules with a pink – orange color when stained with eosin (Ezeilo, 2002).

Basophils

            Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing vasodilation. The nucleus is bilobed or trilobed, but it is hard to see because of the number of coarse granules which hide it. They are characterized by their large blue granules (Ezeilo, 2002).

Lymphocytes

Lymphocytes are much more common in the lymphatic system. Lymphocytes are distinguished by having a deeply staining nucleus which may be eccentric in location and a relatively small amount of cytoplasm.

The blood has 3 types of lymphocytes.

β – Cells: β – cells make antibodies that bind to pathogens to enable their destruction. They do not only make antibodies that bind to pathogens, but after an attack, some B – cells will retain the ability to produce an antibody to serve as a memory system. (Pantaleo et al, 1994).

T – Cells

1)        CD4+ (helper) : T – cells having co – receptors CD4 is known as CD4+ T cells. These cells bind with the antigen having MHC11 receptors on its surface. They present this antigen to β – cells. β – cells produce anti – bodies to destroy antigens. The CD4+T cells is also known as antigen presenting cells. T – cells co – ordinate the immune response and are important in the defense against intracellular bacteria (Pantaleo et al, 1994)

In acute HIV infections, these T – cells are the main index to identifying the individual’s immune system activity. Research has shown that CD8+ cells are also another index to identifying human’s immune activity (Pantaleo et al. 1994).

2)        CD8+ cytotoxic T cells: Are able to kill virus infected and tumor cells. T cells having co – receptors CD8 are known as CD8+ T cells. These cells kill damaged or cancerous cells. CD8 binds with MHC 1 receptors of damaged cells (carrying antigens). All nucleated cells possess MHC1 on its surface (Pantaleo et al, 1994).

3)        YdT –cells: possess an alternative T cell receptors as opposed to CD8+ and CD8+αβT cells and share characteristics of helper T-cells, cytotoxic T-cells and natural killer cells (Pantaleo et al, 1994).

4)        Natural killer cells: Natural killer cells are able to kill cells of the body which are displaying a signal to kill them, as they have been infected by a virus or have become cancerous (Pantaleo et al, 1994).

Monocytes: Is usually the largest leucocytes and is about 15 – 20um in diameter. The Nucleus is often indented or kidney shaped and tends to be pushed to one side of the cell (eccentric). It has a fine meshwork of chromatin which distinguishes it from large lymphocytes.

            The cytoplasm has blue – grey frosted appearance after staining and may be vacuolated (Ezeilo, 2002).

WHITE BLOOD CELL COUNT

Is the number of white blood cells in a volume of blood. Normal range varies slightly between laboratories but it is generally between 4,300 and 10,800 cells per cubic millimeter (cmm). This can also be referred to as the leucocyte count and can be expressed in international units as 4.3 to 10.8 x 10⁹ cells per litre (Siamak, 2011).

            White blood cell differential counts comprises of several different types of cells that are differentiated or distinguished based on their size and shape. The cells on a differential counts are granulocytes, lymphocytes, monocytes, eosinophil and basophils (Siamak, 2011).

The differential and white blood cell counts in Caucasians and African (mean values for differential counts in bracket) is shown below.

(Ezeilo, 1972)

FACTORS THAT AFFECTS THE WHITE BLOOD CELL COUNT

1)        Age

2)        Exercise

3)        Pregnancy

4)        Diurnal variation and menstrual cycle

5)        Emotion

6)        Nutritional factors

            Majority of Negro Africans have on the average lower leucocyte counts compared with those of Caucasians. The low counts are due to lower absolute counts of neutrophils in the Africans. In addition, their eosinophil counts are higher. This alters their differential W.B.C values such that the lymphocytes rather than the neutrophil, is the most abundant leucocyte (Ezeilo,2002).

            Studies have shown that Africans are not neutropenic at birth, and when their diets were changed to Caucasian pattern, remarkable corresponding changes occurred in their leucocytes pattern: an increase in their neutrophil counts with a fall in the eosinophil counts. Studies in experimental animals have shown that changes in diets can have profound effects on blood leucocyte pattern in animals. The neutropenia is therefore believed to be of dietary origin (Ezeilo, 2002).

DISORDERS OF THE WHITE BLOOD CELLS

1)        Leukemia: Also called blood cancer is a group of disease that is caused due to increased number of blood cells. Uncontrolled growth of any blood cell leads to leukemia. Most forms of the disease are caused due to high white blood cell counts. The bone marrow produces a large number of immature white blood cells that cannot function properly. The following is a list of different types of leukemia that occurs due to increased white blood cells in the blood.

1)        Acute myeloid leukemia

2)        Chronic myeloid leukemia

3)        Acute lymphocyte leukemia

4)        Chronic lymphocyte leukemia (Mayuri, 2012)

2)        Lymphoma: is characterized by malignant tumors of lymphocytes that are usually not associated with a leukemia blood picture. Instead enlargement of lymph nodes, spleen, both are characteristics. The lymphomas are classified into 2 main groups;

1)        Hodgkins Disease.

2)        Non – Hodgkin Disease.

Hodgkin disease usually begins with a painless swelling of any lymph nodes; it may involve lymph nodes anywhere in the body.

Non – Hodgkin lymphoma arises from either β – lymphocytes or T– lymphocytes (Maxwell et al 2010).

3)        Leucocytosis: Means an increase in white blood cell counts above the normal range. It may be due to an increase in any cell type eg Neutrophilia or a lymphocytosis and may be physiological or pathological. Pathological leucocytosis may be due to inflammation in which mediators are released from macrophage, neutrophils, endothelial and fibroblast cells which stimulate the marrow to increase leucopoiesis or it may be due to a neoplastic disorder of leucocyte production, a condition known as leukemia (Ezeilo, 2002)

4)        Leucopenia: means a decrease in white blood cell count below normal which may be due to a fall in a particular cell type, e.g. Neutropenia. A sever Neutropenia (Neutrophil count < 500/ul) may cause recurrent pyogenic infections especially in the areas where micro – organisms are in contact with the body, the skin, the anus, mouth and respiratory passages (Ezeilo, 2002).

EFFECTS OF CARBOHYDRATES, PROTEIN AND LIPIDS ON THE LEUCOCYTES

1)        Sanchez et al (1973) reported the “role of sugars in human neutrophilic phagocytosis”, showing that ingesting 100g of simple sugar lowers white blood cell activity for up to 5 hours. He got this result using processed honey, table sugar and processed orange juice. This translates into a 50% reduction in the ability of W.B.C to engulf bacteria. Lowered W.B.C activity means that the immune system and its ability to fight infection is impaired.

2)        Sugar raises the insulin level which inhibits the release of growth hormones which in turn depresses the immune system. An influx of sugar into the blood stream upsets the body’s blood sugar balance triggering the release of insulin, which the body uses to keep blood sugar at a constant and safe level. Sugar can produces a significant rise in triglycerides which have been linked to cardiovascular diseases (Bernstein, 1977, Leeper, 1998).

3)        The effects of dietary proteins and amino acid on the immune system have been documented previously. In particular, dietary caesin proteins are known to enhance the immune system and promote host protection against the development of intestinal cancer (Wong et al, 1995, Mcintosh et al, 1995, Kunz et al . 1990, Parker et al 1984).

Soy is a common plant source of dietary proteins for humans and many mammalian species. It contains a range of phytochemical such as Isoflavons, which influence the activity of the immune system and have anti – tumor activities in animals. For example, Isoflavones influences the signal transduction process of macrophages and other phagocytic cells and the activity of cytotoxic T – lymphocyte, thus influencing both non – specific and specific immune response (Rumsey et al, 1994 and steward et al, 1997).

4)        White blood cells require proteins from the diet to combat antigens. One of the ways immune cells fight against pathogens is by increasing their numbers.

To increase immune cell proliferation, you need proteins and amino acids. To achieve the healthiest possible immune system, consume 0.8 – 1g of proteins per kg of body weight (Eric, 2010).

5)        Diets containing different amounts of caesin (3, 6, 9 and 18%) were fed ad libitum on rats to determine the effects of diet varying in quantity and quality on the white blood cell. At the 3% level, a decrease occurred in the white blood cell count where as the other three (6, 9 and 18) percentages initiated a regeneration of leucocytes, its degree being more or less in proportion to casein content. Therefore protein increases the white blood cell regeneration (Guggenheim 1949).

6)        Johnson et al. (2001) studied the influence of westernized and traditional African diets on biochemical and haematological profiles in vervet monkeys (cercorpithecus aethiops). 12 adult male vervet monkeys, all over 4 years of age and weighing more than 5kg each, were divided into 2 groups of 6 individuals. These monkeys were fed for 8 weeks on diets containing milk solids (17.2%) maize and legume (17.4%) as source of protein. High protein diets had no significant effect on serum biochemical indices and heamatological parameter (W.B.C) for the African diet. Compared to the group that were given the traditional African food, the animals on the western type milk solid diets showed significant elevation in a number of important biological indicators like (Total cholesterol, low density lipoprotein and triglycerides).

7)        The effect of diet on the differential white blood cell counts in rat was studied by Ogunranti, 1994. Twenty rats were divided into 4 dietary groups.  Group 1(Control) rats fed on pallets, group 2 rats fed on Millet,  group 3 rats fed on Peanuts and  group 4 rats fed on a special diet containing high cholesterol and saturated fatty acids from coconuts, egg yolk, milk and Danish butter. After 3 months, group 4 rats had significantly higher total white blood cell counts and percentage neutrophils in addition to higher serum cholesterol levels and higher weights.

8)        Haematological values determined in 3 groups of Africans on different diets were compared with those of groups of European and Asians. Neutropenia was most common in African on native diets (88%), less common in those who periodically had European diets (55%) and least common (25%) in those having only a European diet. Lymphocyte and eosinophil values were higher in the African groups, but the values for Africans on European diets were closest to those of Europeans and Asians. These results suggest that Neutropenia in Africans is non – genetic in origin (Ezeilo, 1972)

9.         Oji, 2011 Studied the influence of different diets on blood leucocyte patterns. He reported that diets high in carbohydrates and low in saturated fat and animal protein are suggested to be responsible for Neutropenia in Africans.