MBM

• Protein buffer used intracellular and extracellular
• Hormones


  Chemical substances that act like messenger molecules in the body. After being made in endocrine gland, they travel to other parts of the body where they help control how cells and organs do their work. They serve in physiolgical regulation and behavioural activities such as digestion, metabolism, respiration, tissue function, growth and development, movement, reproduction

  
• Types of hormone signalling

  • Autocrine - Affects the cell that secreted it (e.g. Insulin & IGF-1)
  • Paracrine - Acts on a nearby cell and does not have to enter general circulation (e.g. Estrogen and testosterone)
  • Endocrine - Acts on the target cell after being released into the bloodstream (e.g. Most hormones such as pituitary hormones)

  
• Classification of hormones

  • Steroid hormones - Derived from cholesterol (e.g. Sex hormones, stress hormone, aldosterone)
  • Amino acid hormones - Derived from amino acid, most commonly tyrosine (e.g. Thyroid hormone, epinephrine, norepinephrine)
  • Peptide or protein hormones - Made of a chain of amino acids (e.g. Oxytocin, glucagon, insulin)
• Hypothalamus


  • Controls the body temperature, regulates emotions, hunger, thirst, sleep, moods and allows the production of hormones. Contains neurosecretory cells that secrete neurohormones to stimulate the anterior lobe of the pituitary to produce various other hormones
• Pituitary gland

  • Also termed as the "master control gland". Develops the hormones that trigger growth and development. The anterior lobe regulates growth, metabolism, and reproduction through the hormones it produces (e.g. Growth hormone, Thyroid-stimulating hormone, Adrenocorticotropic hormone, Follicle-stimulating hormone, Luteinizing hormone, Prolactin). The posterior lobe produces vasopressin and oxytocin
• Testes

  • In men, secrete the male sex hormone testosterone. Also produces sperm. Testosterone helps develop and maintain male sex characteristics
• Ovaries

  • In the female reproductive system, release estrogen, progesterone, testosterone and other female sex hormones. Estrogen and progesterone regulate the development and function of the uterus
• Other endocrine glands

  • Parathyroid - Controls the amount of calcium in the body
  • Thyroid - Produces hormones that affect the heart rate and how calories are burnt
  • Adrenal - Cortex produces cortisol, aldosterone, and androgen. Medulla produces adrenaline and noradrenaline
  • Pancreas - Produces insulin and glucagon to maintain blood sugar levels
  • Thymus - Helps in the production of T-cells, functioning of the adaptive immune system
  • Pineal - Produces serotonin derivatives of melatonin, which affects sleep patterns

  
• The rate of hormone biosynthesis and secretion is often regulated by a homeostatic negative feedback control mechanism

  
• Thyrotropin releasing hormone (TRH) – thyroid stimulating hormone (TSH – Triiodothyronine /Tetraiodothyronine (T3/T4)


  1. TRH

  2. TSH

  3. T3/T4
• Thyroid disorders

  • Hyperthyroidism (Graves' disease)
  • Hypothyroidism (Cretinism)
• Hormonal assay for thyroid disease

  • TSH
  • T3
  • T4
• Gonadotropin releasing hormone (GnRH) – Luteinizing hormone/follicule stimulating hormone (LH/FSH) - sex hormones


  1. GnRH

  2. LH/FSH

  3. Sex hormones
• Hormonal assay for assessment of male infertility

  • LH
  • FSH
  • Testosterone
• Hormonal assay for assessment of female infertility

  • LH
  • FSH
  • Estrogen
• Corticotropin releasing hormone (CRH) - Adrenocorticotropic hormone (ACTH) – Cortisol axis


  1. CRH

  2. ACTH

  3. Cortisol
• Lab investigations for Cushing Syndrome

  • Blood cortisol (measurement at night)
  • 24 hrs. urine cortisol

  
• Growth hormone (GH) axis


  • Gigantism (GH hypersecretion before epiphysis fusion)
  • Acromegaly (GH hypersecretion after epiphysis fusion)
• Gigantism does not turn into acromegaly. That's because each disorder is defined by the age when it begins.
• Growth hormone deficiency (GHD)

  Condition caused by insufficient amounts of growth hormone in the body, also known as dwarfism or pituitary dwarfism
• Regulation of blood calcium

  1. Primary hyperparathyroidism

  2. Secondary hyperparathyroidism
• Hypoparathyroidism


  Occurs when the parathyroid glands don't produce enough parathyroid hormone
• Dysglycemia


  Abnormality in blood sugar stability, including hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar)
• Causes of dysglycemia

  • Type 1 diabetes
  • Type 2 diabetes
  • Gestational diabetes
  • Prediabetes
  • Conditions affecting liver or kidneys
  • Endocrine disorders, such as adrenal gland deficiency
  • Eating disorders, such as anorexia
  • Malnutrition
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

  Condition in which the body makes too much antidiuretic hormone, causing the body to retain too much water and dilute substances in the blood such as sodium
• The objective is to: 1) State the Tricarboxylic acid cycle (TCA) and diagram the steps that produce reduced coenzymes and high energy phosphate compounds, 2) Explain TCA regulation and name the intermediate compound that link other pathways, 3) State the electron transport chain describing the transport of electron and site of inhibition, 4) Correlate abnormalities of TCA and ETC with some core clinical problems and inhibitors

  
• Citric Acid Cycle (Tricarboxylic Acid Cycle or Krebs' Cycle)


  A series of reactions responsible for the complete oxidation of the acetyl moiety of acetyl-CoA. It is the final common pathway for the oxidation of carbohydrates, lipids and proteins

  
• Citric Acid Cycle

  • The enzymes are found in the mitochondrial matrix except succinate dehydrogenase which is tightly bound to the inner mitochondrial membrane
  • The enzymes are in close proximity to the enzymes of the respiratory chain

  
• Citric Acid Cycle

  1. Oxaloacetic acid

  2. Citric acid

  3. Isocitric acid

  4. Alpha-ketoglutaric acid

  5. Succinyl CoA

  6. Succinic acid

  7. Fumaric acid

  8. Malic acid

  9. Oxaloacetic acid

  
• During the oxidation of acetyl-CoA, coenzymes (NAD and FAD) are reduced and subsequently reoxidized in the respiratory chain with the formation of ATP
• Regulation of Citric Acid Cycle

  The 3 important regulatory enzymes are: 1) Citrate Synthase, 2) Isocitrate Dehydrogenase, 3) α Keto glutarate Dehydrogenase

  The cycle is inhibited when ATP, NADH, Succinyl CoA are high, ADP acts as an activator

  Genetic defects of enzymes are associated with severe Neurological damage due to high decreasing in ATP formation in CNS
• Excess citrate formation

  Can move out of mitochondria and be reconverted into Acetyl CoA, a precursor of fatty acids synthesis, leading to lipogenesis and obesity

  
• Regulation of Citric Acid Cycle

  • Regulated by enzymes, vitamins, and feedback

  Pathological cases: deficiency of enzymes, coenzymes, oxygen, substrates, or effect of chemical inhibitors

  
• Integration of metabolism

  The citric acid cycle is amphibolic (both catabolic and anabolic)

  Yields energy in the form of GTP (ATP)

  Yields reducing power in the form of NADH2 and FADH2

  
• The citric acid cycle is involved in the aerobic catabolism of carbohydrates, lipids and amino acids. Intermediates of the cycle are starting points for many anabolic reactions.

  
• Genesis pathway

  Pathway in liver to go into adipose tissues to be stored causing Obesity
• Lipogenesis

  Anabolic pathway
• Pathological cases

  • Deficiency of an enzyme due to inherited disorder
  • Deficiency of a coenzyme due to nutritional deficiency
  • Deficiency of oxygen
  • Deficiency of substrates
  • Effect of chemical inhibitor
• Citric acid cycle

  • Amphibolic (both catabolic and anabolic)
  • Involved in the aerobic catabolism of carbohydrates, lipids and amino acids
  • Intermediates are starting points for many anabolic reactions
  • Yields energy in the form of GTP (ATP)
  • Yields reducing power in the form of NADH2 and FADH2