Human Cell Biology and Physiology

Human Cell Biology and Physiology Timothy Billington PhD

SILVER LINING? WHO NEEDS IT?

FIFTH FORMATIVE TEST 10th November 2016 • 1. A hypothetical membrane interface exists between a cell and a capillary. The following values for partial pressures (mm mercury, Hg) of gases A and B are measured: • p p Gas A (cell) 50, (capillary), 65. p p Gas B (cell) 50, (capillary) 35. • Predict the direction of diffusion for each gas. • 2. Atmospheric pressure at sea level is 760 mmHg. Percent composition of 4 gases in the atmosphere is: • Nitrogen, 78., Oxygen, 21., Carbon Dioxide, 0.03., Argon, 0.93. What partial pressure does each of the 4 gases contribute to the total pressure? • 3. Carbon Dioxide is transported in the blood stream in 3 ways. Name them and write down any possible reactions that the gas could undergo, once in the blood stream. • 4. Little Cindy is angry with her mother so she tells her mother that she will hold her breath until she turns blue and dies. Should her mother be concerned?

5. Compare and describe External respiration and Internal respiration. • 6. Name the Special Senses and the type of nerve pathway common to all. • 7. Name and describe the receptor structure which operates in gustatory detection. • 8. From your knowledge of vision receptors, explain why it is difficult to see colour when reading by weak moonlight. • 9. What is the reason that we describe the heart as a double pump? Describe the two circuits serviced by this pump. • 10. A ‘30 something’ woman goes to her GP because she is feeling unusually tired and lacks her usual energy. GP tests her blood and tells her that she is anaemic. Explain why anaemia can lead to lack of energy and tiredness. • 11. The ear senses sound waves AND motion & position of the head. Describe the cellular receptor structures operating in both these senses. • 12. Why do we use venepuncture for obtaining a blood sample, in preference to arterial puncture? • 13. Relate the structure of Haemoglobin to its function in oxygen transport

Week 8 begins here IntroductiontoCellular Metabolism

DIET Carbohydrates Proteins Fats Free fatty acids + glycerol Protein synthesis Glycogenesis Amino acids Glucose Fat stores Lipogenesis Excess glucose Body protein Lipogenesis Glycogen stores Urine Lipolysis Glycogenolysis Glucose pool Gluconeogenesis Free fatty acid pool Range of normal plasma glucose Amino acid pool Metabolism in most tissues Brain metabolism Excess nutrients Physiologist’s view of Metabolism

Metabolism is the sum of allchemical reactions in the body OCCUR INSIDE CELLS

Let’s look at some REAL chemistry

Biochemist’s view of Metabolism Glucose Pyruvic Acid

You see that our anaerobic friend Glycolysis (Glucose Pyruvate ) is only a small part of overall cellular metabolism

Q. WHAT DO WE MEAN BY ANAEROBIC? Q. IN WHICH ORGANELLE DOES AEROBIC METABOLISM OCCUR

Metabolism by cells provides the energy needed to: 1. maintain homeostasis 2. perform essential biochemical functions Essential functions include: • Metabolic turnover= periodic breakdown & replacement of the cell’s organic components • Growth and cell division • Special processes, ( secretion, contraction and the propagation of action potentials)

Amino acids, monosaccharides and fatty acids enter the cell via the cell membrane. Join those already in the cytoplasm Nutrient Pool Contains all the cell’s required organic building blocks Cell draws on this pool to provide energy and to create new, or repair, intracellular components

How does the body extract energy from food ? The Cell ? ? ?

Duality of Metabolism CatabolicandAnabolic pathways

High energy level Low energy level Low energy level

ANABOLISM= SYNTHESIS of an END PRODUCT Synthesis alwaysCONSUMES energy CATABOLISM = BREAKDOWN of a COMPLEX MOLECULE into a SIMPLER MOLECULE Breakdown reactions alwaysYIELD energy

HOW are Anabolism and Catabolism coupled in the cell ? ?

Couplingofcatabolismwithanabolism

GROWTH Consider the elapsed time between Fertilisation and Physical Maturity Enormous changes in complexity and organisation Fertilisation: you have one cell Physical maturity: ~ 70 trillion cells

TO ACCOMPLISH THIS TRANSFORMATION WE NEED CELLULAR REPRODUCTION Cellular reproduction occurs by CELL DIVISION We shall look at the nucleardivision process called MITOSIS Division of a single cell produces 2 daughter cells, each half the size of the parent cell Genetic characteristics of each daughter cell are identical to those of the parent cell DNA must be copied Duplication of the cell’s genetic material is called DNA replication

Model of a DNA double helix Think of DNA as the Molecule of Inheritance

DNA in Human Cells • Human cells have a cell nucleus in which DNA is condensed & packaged • DNA is organised into chromosomeseach representing one long DNA molecule, combined with proteins called histones

Human chromosomes as they appear in the nucleus ( unsorted )

HUMAN CHROMOSOMES: COMPLETE SET = 46 Stained with fluorescent dyes to aid identification of pairs

LET’S LOOK AT THE ULTRASTRUCTURE OF A TYPICAL CHROMOSOME

WHAT is the RELATIONSHIP b/w a CHROMOSOME and a GENE? Let us look graphically at chromosome # 22 We will gradually subdivide it, down to just ONE gene

From Chromosome to Gene and Gene to Gene Product This represents just 10% of the long arm of chromosome 22 Coding regions: 2%

From Chromosome to Gene and Gene to Gene Product We now see what is in this next 10% Coding regions: 2%

From Chromosome to Gene and Gene to Gene Product We will look at ONE of these 4 genes and its Gene Product Gene Product = an amino acid chain Protein = a FOLDED amino acid chain Coding regions: 2%

From Chromosome to Gene and Gene to Gene Product Coding regions: 2%

Now let’s return to the general properties of DNA

DNA strand structure Deoxyribonucleic acid = linear polymer of 4 different nucleotides arranged in a specific sequence. Each nucleotide= one of the four nitrogenous bases, plus a deoxyribose sugar molecule The deoxy-ribo-nucleotides are linked to each other by phospho-di-ester bonds. O-P-O SEQUENCE of nucleotidesencodes thegenetic information.

DNA Double Helix – Properties • 2polynucleotide chains are paired in anti-parallel manner, around an imaginary common axis. • Nucleotide bases are internal • Sugar phosphate backbone is on the outside • Strands are held together by hydrogen bonds between the nucleotide bases. Hydrogen bonds can be likened to the horizontal rungs of a spiral ladder.

DNA: base-pairing via hydrogen bonds Nucleotide bases (C&T) Hydrogen bonding Nucleotide bases (A&G) Base-pairing rules: Aonlypairs with T , Conlypairs with G

DNA Double Helix – Properties • Base-pairing rules (A = T and C = G)predict • (1) the two strands complement each other • (2) the base sequence of one strand can be derivedfrom that of the other DNA Polymerase uses one strand as a template and derives a complementary strand

DNA Helicase being synthesis New strands being synthesised DNA Polymerase DNA REPLICATION Double helix is unwound by an enzyme called DNA Helicase Eachof the resulting single strands is then used as a template for the synthesis of a complementary new strand by DNA Polymerase

RESULT IS: 2 double helices Each helix is made up of a parental strand and a newly-synthesised (daughter) strand

DNA replication Original double helix Replication is semi-conservative Helica Parental strands Daughter molecules

CELL DIVISION – MITOSIS Mitosis is the duplication of the 46 chromosomes in the human cell nucleus and their subsequent separation into 2 identical sets A single cell has divided and produced 2 daughter cells Both daughter cells have identical DNA.

CELL DIVISION Even when physical development is complete, cell division must continue Essential to survival Cells are subjected to: physical wear and tear toxic chemicals temperature changes/ extremes other environmental stressors Cells age: Life span may be hours or decades Some cells self-destruct, controlled by the action of ‘suicide’ genes

APOPTOSIS = Genetically-controlled cell death

Human Cell Biology and Physiology