PROTEINS: STRUCTURE AND FUNCTION <---- SAME NAME !!!!! + IT'S ALL JESSE CHAN !!! (threw away all protein notes....)

• Diversity of Functions

Amino acids, proteins, peptide bonds

• Protein Structure 

Primary structure

Secondary structure (β-pleatedsheet, α-helix)

Tertiary structure (different types of interactions)

Quaternary structure

• Other Levels of Organisation

Supersecondary structure, domains

• Protein Conformation

Denaturation

Diseases/disorders associated with protein folding

(a) Loss of protein activity (collagen disorders, cystic fibrosis, p53)

(b) Aggregates

(i) amyloid disorders (Alzheimer's, prions)

(ii) non-amyloid disorders (Huntingdon's, Parkinson's, cataracts)

• Relationship Between Protein Structure (Shape) and Function

(a) Fibrous proteins (α-keratin, collagen)

(b) Globular proteins - major types of secondary structure elements occur in globular proteins in varying proportions and combinations (examples)

• Enzyme Proteins

Enzymes as catalysts.  How do enzymes work?  The active site.  Enzyme-substrate complex. Substrate specificity.  Factors affecting enzyme activity in vivo (substrate concentration, enzyme concentration,temperature, pH).

Feedback regulation

Allosteric regulation

• Post-Translational Modification

(a) Reversible covalent modification

(b)Proteolytic activation (zymogens)

(c)Other modifications (acetyl groups,hydroxyl, carbohydrate)

- Coenzymes and cofactors

-Isoenzymes (LDH)

-Multi-enzyme complexes

- Receptor-ligand binding

NITROGEN METABOLISM <--- Intro to Biochem deee

• Nitrogen Turnover

Nitrogen balance, positive and negative nitrogen balance, nitrogen turnover, ruminant nitrogen metabolism and inter-tissue relationships.

• Amino Acid Nitrogen Metabolism

Catabolism of amino acids; transamination; pyridoxal phosphate; oxidative deamination, glutamate dehydrogenase and direct deamination.

• Nitrogen Excretion

Ammonia toxicity, reactions of the urea cycle, inborn errors in urea cycle, urea, uric acid, ammonia and comparative aspects of excretory processes in fish, reptiles, birds and mammals.

• Amino Acid Carbon Metabolism

Glycogenic and ketogenic amino acid, routes of oxidation of carbon skeletons, biosynthesis of amino acids, essential and non-essential amino acids, glutamate dehydrogenase, glutamine synthase, carbomoyl phosphate synthase, amino acid biosynthsis and the citric acid cycle. Amino acids as precursors of other compounds (e.g. taurin, niacin, creatine, purines and pyrimidines).

CARBOHYDRATES <---

• Basic Metabolic Concepts

Intermediary metabolism

Coupling of endergonic and exergonic reactions

ATP and creatine phosphate

NAD ⁺ , FAD ⁺ , NADPH, Coenzyme-A

Extraction of energy from foodstuffs

Mitochondrial electron transport and oxidative phosphorylation

• Metabolism of Carbohydrates

Pathways of hexose metabolism (outline)

Storage of glycogen; glycogen structure

Glycogen metabolism: glycogenesis and glycogenolysis

Hormonal control of glycogen metabolism (liver and muscle)

Glucose uptake by cells - insulin, glucose tranporters

Glycogen disease

• Catabolism (Breakdown) of Glucose

Pathways of glucose 6-phosphate metabolism

Free glucose pathway; Cori cycle

Glycogenesis (glycogen synthesis) pathway

Glycolysis - anaerobic, regulation, aerobic

Citric Acid Cycle: yield of ATP

Pentose Phosphate Pathway (generation of NADPH)

Citric Acid Cycle as a source of biosynthetic precursors

Reasons for occurrence of ketogenesis

• Gluconeogenesis (glucose from non-carbohydrate precursors)

Sources of carbon (including proprionate)

Reactions of gluconeogenesis

Some interrelationships involving the Citric Acid Cycle

Propionate, acetate and butyrate as sources of energy

• Disorders of Carbohydrate Metabolism

Diabetes

Hyperinsulinism

Hypoglycemia of new-born pigs

Glycogen storage diseases

Disorders of ruminants associated with hypoglycemia

(i) Bovine ketosis

(ii) Ovine pregnancy toxemia

(iii) Carbohydrate balance

- glucose requirements

- glucose sou rces (acetate, propionate, butyrate)

- utilisation of glucose

- mammary gland

- ruminant nervous tissue (brain)

- gluconeogenic enzymes and ketosis in dairy cattle and pregnant ewes

LIPID METABOLISM <--- 

• Lipid Classes and Structures

Introduction to lipids - define key terms, description of different lipid classes

Fatty acids, triglycerides, cholesterol, phospholipids and glycolipids

Overview of lipid structures

Physiological functions of lipids classes in animals

• Lipid Digestion in Monogastrics

Digestion and absorption of dietary lipids. The role of lipases and bile.

Transport of lipids from gut to tissues - an introduction to lipoprotein classes

Lipoprotein structure, chemical properties and functions

Overview of lipoprotein (LDL) - rec eptor-mediated endocytosis

Fate of internalised lipids

Lipoproteins and disease in animals e.g. hypercholesterolaemia

• Lipid Digestion in Ruminants

Introduction to volatile fatty acid production in rumen

Metabolic fate of acetic acid, propionic acid and butyric acid in ruminants

The use of volatile fatty acids as energy sources

• Lipid Metabolism: Lipids as an Energy Source and Energy Store

Basic concepts of lipid metabolism

The link between lipid and carbohydrate metabolism

Lipids as energy store - comparison with carbohydrates (glycogen)

Description of the use of lipids as energy source

Mobilisation, activation and metabolism of fatty acids in animals

The metabolic process of B-oxidation and the generation of energy

The importance of B-oxidation in animal physiology e.g. as an energy source and water supply in hibernating bears and migrating birds

• Introduction to Ketone Bodies

The synthesis and metabolism of ketone bodies in animals

Ketone bodies and animal disease

Diabetes mellitus in cats and dogs

Bovine ketosis

Ovine pregnancy toxaemia

• Biosynthesis of Lipids

Introduction to de novo synthesis of lipids (as opposed to dietary intake)

Introduction to essential fatty acids

The biosynthesis of fatty acids in animals

Fatty acid synthase, elongation and desaturation of fatty acids

Fatty acid utilisation in animals - completes theme started in earlier lectures

at least there's no plant pathways......

CELLULAR SIGNALLING <--- Cell Bio!!!

• Hormones, Neurotransmitters and Local Mediators

Cellular communications, endocrine hormones, paracrine hormones, neurotransmitters, water-soluble hormones, lipid soluble hormones and hormone receptors

• Secondary Messengers and cAMP Intracellular Signalling System

The classical secondary messenger model, the B-adrenergic receptor, G-proteins, adenylate cyclase and phosphodiesterases, cAMP-dependant protein kinase and protein phosphatases. The hormonal control of glycogen metabolism.

• The Insulin Receptor

The metabolic effec ts of insulin, receptor tyrosine kinases, the insulin receptor, insulin and glucose transport, insulin and glycogen metabolism.

• The Role of Calcium in Intracellular Signalling

Intracellular calcium stores, calcium mobilisation, phosphodiesterase C, phosphoinositides, diacylglycerol, inositol triphosphate, calmodulin.

• Signal Transduction by Nuclear Receptors

Steroid hormones and transcription factors, androgens, estrogens, glucocorticoids, steroid hormones and gene expression, the estrogen receptor, steroid hormones and drug design, veterinary uses of steroid hormones.

PRINCIPLES OF PHARMACOLOGY <--- chem... 

Basic Pharmacology

• Agonists and the Concept of Receptors

Graded dose-response curves

Efficacy and affinity

• Antagonists: Competitive and Non-Competitive
• Partial Agonists and Spare Receptors
• Quantal Dose-Response Curves

Indices of Safety - T.I .

• Introduction of Qualitative Pharmacokinetics

Interaction of absorption, distribution, metabolism and excretion and effects on plasma drug concentration

Factors affecting diffusion of d rugs across membranes

Lipid solubility (re: the barbiturates), degree of ionisation

• Henderson-Hasselbach Equation in Relation to Drugs

Effect of pH on drug absorption, distribution and excretion

• Absorption and Bioavailability

First-pass effect with oral dosing

• Hepatic Metabolism: Phases 1 and 2

Factors affecting metabolism

Tolerance and tachyphylaxis

• Renal Excretion (pH effects)

Bi liary excretion and entero-hepatic recycluing

• Introduction fo quantitative pharmacokinetics

Comparative analysis

• Exponential Decay and Plasma Half-Life

Volume of distribution and clearance

First-order versus zero-order elimination

Implications for multiple dosing regimes

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