Metabolism, Disease and Cancer Flashcards
1
Q
What are the types of diabetes mellitus and long term risks
A
- Type 1: Insufficient production of insulin, autoimmune destruction of b cells, weight loss, increased urination / thirst, ketoacidosis, altered breathing
- Type 2: Insulin resistance, associated with obesity, cells don’t respond to insulin, obesity, high BP / BG, inflammation
- Increases the risk of cardiovascular disease, renal failure, and damage to small blood vessels and nerves
2
Q
What is metabolic disease
A
- Syndrome X
- Cluster of disorders of metabolism
- Including, high BP, elevated insulin levels, obesity and abnormal cholesterol levels
- Each of these disorders is by itself a risk factor for other diseases
- In combination, these disorders dramatically boost the chances of developing potentially life-threatening illnesses (diabetes,heart disease, stroke)
3
Q
What is obesity, what is it influenced by and what cells are affected
A
- Obesity: Metabolic Syndrome largely linked to obesity, energy storage issue, regulated by hormones
- Influenced by appetite and eating behaviour, exercise, metabolic processing of fuel
- Adipocytes: Influence brain’s decision making about food intake and energy expenditure via the protein hormone leptin
- Adipose Tissue: Fat stored in the adipose tissue, endocrine organ, releases peptide adipokines
- Adipokines: Carry information about fuel stores to brain key ones are leptin & adiponectin
4
Q
What is adiponectin
A
- Made by adipose tissue, receptors in brain
- Makes other organs sensitive to insulin
- Works via AMP-activated kinase pathway, bottom up
- AMPK phosphorylates and inactivates acetyl-CoA carboxylase
- Enzyme normally makes malonyl-CoA
- Malonyl-CoA inhibits fatty acid import into mitochondria
- Reduced acetyl-CoA carboxylase means that fatty acids are free to enter the mitochondria for oxidation
- AMPK pathway also inhibits cholesterol synthesis
5
Q
What is leptin
A
- Appetite suppressant, sent from adipose tissue to the brain (reduces appetite)
- Inhibits synthesis of fat and causes b oxidation of fat to energy / heat
- Inhibits neuropeptide Y (appetite stimulating)
- Stimulates release of a-MSH (appetite suppressant)
- Stimulate release of norepinephrine and increase transcription of UCP1 gene
- UCP1 increases thermogenesis, heat released without energy, increased fat loss
6
Q
What is ghrelin
A
- Short term orexigenic peptide secreted into stomach
- Receptors in brain, heart and adipose tissue
- Works via GPCRs to increase sensation of hunger
- Prader-Willi syndrome associated with high levels of ghrelin and insatiable appetite
7
Q
What occurs when adipocytes are overloaded
A
- Lean: TAG diet = TAG catabolised
- Overweight: TAG diet > TAG catabolised
- Pro-Inflammatory: Enlarged adipocyte produce MCP-1, increased FFAs enter glycolysis
- Chronic Inflammation: Macrophages infiltrate adipose tissue, produce TNF-a, increases FFAs export, ectopic lipid deposits build up in muscle, lipids interfere with GLUT4 leading to insulin resistance
8
Q
How is type 2 diabetes treated
A
- Diet and exercise to reduce obesity, manage BG, increase insulin sensitivity of muscles
- PPAR activators to increase adiponectin
- Stimulation of insulin by binding ATP gated K channels
- Prevent proteolytic degradation of GLP1 (promotes insulin secretion)
9
Q
Describe normal cellular development
A
- Intricate genetic control systems regulate the balance between cell birth and cell death in response to growth signals, growth-inhibiting signals, and death signals
- Normal cell proliferation is modulated by regulation of the cell cycle, apoptosis eliminates damaged cells
- Normal cell numbers are tightly regulated
10
Q
Describe tumour cell development
A
- Mechanisms that maintain normal proliferation rates malfunction to cause excess cell division
- Genome changes (point mutations, deletions, amplification)
- Solid tumours (complex, different cell types, interact with environment to obtain a maximal growth advantage)
- Metastatic tumour cells (invade surrounding tissues)
- Highly abnormal karyotypes, genetic makeup dramatically altered, individual chromosome number is altered
11
Q
What is carcinogenesis
A
- Sustain proliferative signalling
- Evade growth suppressors
- Resist cell death
- Activate invasion and metastasis
- Enable replicative immortality
- Induce angiogenesis
12
Q
What are metastatic cancer cells
A
- Invade surrounding tissues
- Migrate on extracellular matrix (ECM) fibres away from the primary tumour to reach BV
- Attracted by signals such as epidermal growth factor (EGF), which can be secreted by macrophages
- Penetrate BV endothelial cell layer that forms the vessel walls and enter the bloodstream
- Example: Carcinoma cells
13
Q
Describe the genetic basis of cancer
A
- Cancer Promoting Mutations: Increase ability of cell to proliferate, decrease susceptibility of cell to apoptosis, increase general mutation rate in cell or its longevity, increase in cell longevity
- Dominant Gain-of-Function: Mutations in protooncogenes, encode growth-promoting signalling proteins and their receptors, signal-transducing proteins, TFs, and anti-apoptotic proteins
- Recessive Loss-of-Function: Mutations in tumour-suppressor genes contribute to cancer, tumour-suppressor genes encode proteins that directly or indirectly control cell-cycle progression
14
Q
What 7 mutagens in protein types cause cancer
A
- Oncogenes: Proteins that normally promote cell growth, extracellular signalling molecules (1), signal receptors (2), signal-transducing proteins (3), transcription factors (4)
- Tumour-Suppressor Gene Mutations: Cell-cycle control proteins which function to restrain cell proliferation (5), DNA-repair proteins (6)
- Oncogenes and Tumour-Suppressor Genes: Apoptotic proteins(7)
15
Q
What is PYY3-36
A
- Hormone secreted from the small intestine and colon, appetite-suppressing hormone
- Named because 36 aa peptide with two Tyr (Y) residues at end
- Secreted in response to food entering stomach, transported to hypothalamus
- Inhibits release of orexigenic NPY, result is reduced hunger
