Metabolic fuels and Dietary components Lecture - 6 By Dr. Abdulrahman Al-Ajlan 1

Glycolysis  The glycolytic pathway is found by all tissues for breakdown of glucose to provide energy in the form of ATP and f intermediates for other metabolic pathway. 2

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 The TCA cycle (Tricarboxylic Acid, Citric Acid, or Krebs) cycle is the major energy-producing pathway in the body.  It occurs in mitochondria.  The foodstuffs that are oxidized feed into the cycle as acetyl Co A, for generate energy through this cycle.  The cycle serves in the synthesis of fatty acids, amino acids, and glucose. TCA Cycle 5

 The TCA cycle starts with 4- carbon compound oxaloacetate, adds 2 carbons from acetyl Co A, loses 2 carbons as CO 2, and generates the 4-carbon compound oxaloacetate.  As acetyl Co A is oxidized to CO 2, electrons are donated to the oxidation-reduction coenzymes, FAD and NAD. 6

 There NADH, FADH, and GTP are produced in the TCA cycle.  The NADH and FADH generated ATP by donating the electrons to O 2 in the process of oxidative phosphorylation. ATP is also produced from the GTP.  One turn of the cycle of generates 12 ATP. 7

 1. Diabetes mellitus  Types of diabetes mellitus A.IDDM (type 1) may accounts for 15% of all diagnosed cases of diabetes. It can occur at any age but most common in early teenage years (9-14 years). In type 1 the pancreas makes little or no insulin due to autoimmune destruction of insulin producing β-cells, genetic and environmental factors such as a viral infection. Clinical Notes: 8

B.B Type 2 (NIDDM), may account for 85% of all diagnosed cases of diabetes and most often occurs in adult (40-80 years). Risk factors for type 2 diabetes include older age, obesity, and family history of diabetes. In type 2 the insulin level may be normal or even high. Obesity is the most commonly associated clinical feature. 9

C.Gestational diabetes; It develops in 2 to 5% of all pregnancies but disappears when a pregnancy is over. Women who have had gestational diabetes are increased risk for later developing type 2 diabetes. Nearly 40% of women with a history of gestational diabetes develop diabetes in future. 10

 Phenyl Ketonuria (PKU)  The reaction above, catalyzed by phenyl alanine hydroxylase, It the first reaction in catabolism of phenyl alanine. Deficiency of phenyl hydroxylase, phenyl accumulates and it converted to compound such as the phenyl ketone, which give the urine a musty odor, mental retardation, failure to walk or talk, hyperactivity and failure to grow occurs. PKU is treated by restriction of Phe in diet. The complete neuralgic damage can be prevented. 11

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 About 15% to 20% of the calories contained in the western diet are supplied by fructose (about 100g/day). The major source of fructose is  Disacchariede sucrose (table sugar). Fructose is also found as a free monosaccharide in many fruits and vegetables and in honey. Entry of fructose into cells is not insulin dependent.  Fructose is metabolized in the liver where it is converted to pyruvate or under fasting conditions to glucose. 13

 In mild or treated diabetes, fructose is suitable source of energy because its metabolism is insulin-independent and the oxidation of fructose via glycolysis and TCA cycle is favored. In severe diabetes, the flux is towards the synthesis of glucose, and fructose instead of being helpful will be detrimental to the patient.  In the eye lens, sorbitol synthesized from the excess glucose may promote cataract development. 14

Metabolism of galactose:  The major dietary source of galactose is the disaccharide lactose found in milk or milk products. Some galactose can also be obtained by degradation of complex carbohydrates such as glycoproteins and glycolipids, which are important membrane components.  UDP-galactose may be reacting with glucose in the mammary gland to produce the milk sugar lactose. 15

Galactosemia:  The appearance of high concentration of galactose in the blood after lactose ingestion may be due to galactokinase deficiency or to an uridyl transferase deficiency. In both condition, excess galactose may reduce to galactitol in nerve tissue, lens, liver and kidney causing severe liver damage, severe mental retardation and cataract.  Babies with this deficiency have severe vomiting and diarrhea.  Therapy: rapid diagnosis and removal of galactose and lactose from the diet. 16

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