Lectures 29/30: Integration of Metabolism Flashcards

Question

Alcohol intoxication and hypoglycemia

Answer 1

Ethanol is metabolized in cytosol to acetyl-CoA, generating NADH Malate dehyrodgenase reaction is prevented from proceeding from matte and NAD+ to oxaloacetate and NADH: inhibition of gluconeogenesis in the liver When this occurs in fasting period, blood glucose levels can drop leading to hypoglycaemia and unconsciousness

Answer 2

1. Regulation of energy levels in the cell (ATP, AMP) 2. Regulation to avoid build-up or scarcity of metabolites: regulation through allosteric effectors and substrate availability

Answer 3

Coordination of metabolism in different cell types/different tissues regarding energy and metabolite levels Regulation through hormone signalling leading to changes in enzyme activity through covalent modification and changes in expression 1. Each tissue must recieve suffice energy in a form it can use 2. Build up of metabolites in body must be prevented 3. Xenobiotics must be degraded

Answer 4

Highest caloric value per carbon Most abundant stored energy in human body (triacylglycerol) Last longest during fasting periods No fatty acid oxidation in absence of oxygen or mitochondria No fatty acid oxidation i brain Cannot be converted to glucose

Answer 5

``` Used by all tissues Limited storage in form of glycogen Can generate ATP even when oxygen is low Precursor for all other metabolites Also needed in pentose phosphate pathway ```

Answer 6

Glycogenic amino acids are nearly as versatile as glucose | Most amino acid storage is in muscle protein, not beneficial to break this down

Answer 7

Remove glucose form blood | Store energy for later

Answer 8

Provide glucose to the tissues that need glucose | Provide energy to other issues, maintain glucose levels in blood

Answer 9

Provide glucose to the tissues that need glucose Provide energy to other issues, maintain glucose levels in blood Reduce glucose requirements as much as possible

Answer 10

Provide energy to muscle | Increase oxygen supply to muscle

Answer 11

Fatty acids and glycerol

Answer 12

Lactate and amino acids

Answer 13

Glucose, ketone bodies, lipoproteins

Answer 14

``` Virtually no energy storage No fatty acid oxidation Glucose is obligatory fuel No secretion of energy metabolites Ketone bodies used when present ```

Answer 15

Virtually no energy storage Fatty acids or glucose used No secretion of energy metabolites Ketone bodies used when present

Answer 16

Ketone bodies only cover 70% of what brain needs, brain will still need glucose

Answer 17

Uptake of glucose and fatty acids Synthesis of TG Removal of blood glucose after a meal Storage of energy for later

Answer 18

Lipolysis of TG Secretion of fatty acids and glycerol Provision of energy during fasting

Answer 19

Glucose uptake, storage as glycogen | Amino acid uptake for protein synthesis

Answer 20

Protein breakdown Amino acids (as alanine) to liver At rest: fatty acid oxidation Ketone bodies used if present

Answer 21

Glycogenolysis Anaerobic glycolysis Secretion of lactate Fatty acid oxidation if sufficient oxygen

Answer 22

Some gluconeogenesis Glutamine breakdown and excretion of ammonium Excretion (NOT production) of urea

Answer 23

Glycogen synthesis and storage, but glucose uptake is not unregulated Glycolysis Fatty acid synthesis from excess acetyl-CoA Triacylglycerol synthesis and secretion as VLDL

Answer 24

Glycogenolysis Secretion of glucose Gluconeogenesis Ketogenesis (when fasting is prolonged VLDL secretion to provide triacylglycerols/fatty acids and cholesterol to heart and skeletal muscle Urea cycle (also active when lost of amino acids are degraded)

Answer 25

Can lead to hypoglycaemia during fasting due to insufficient gluconeogenesis and increased ammonium levels

Answer 26

Transport of lactate from muscle to liver where it is converted to pyruvate and then glucose and released

Answer 27

Pyruvate is produced by muscle glycolysis Pyruvate is transaminate to make alanine Alanine is transported from muscle to the liver where ammonium is released to urea cycle and pyruvate is used to make glucose

Answer 28

Convey short and long-range signals Can be polypeptides, amino acid derivatives, steroids Signalling through specific receptors: maintenance of homeostasis, integration across organism Response to external stimuli Follow cyclic programs: sleep/wake, menstrual Signalling: bind receptor, mediate response, terminate signal

Answer 29

Ligand binds receptor Intracellular signal propagation: activation of enzymes, formation of second messengers, secondary activation enzymes, protein translocation Causes: cytoskeleton rearrangement, enzyme modification, gene expression changes

Answer 30

Ion channels | Neurotransmitters

Answer 31

Over 800 Catecholamines Glucagon Vision, taste, smell

Answer 32

Cytokines: inflammatory molecules

Answer 33

Insulin | Growth factors

Answer 34

Membrane-permeable ligands Steroids Thyroid hormones Vitamins A, D

Answer 35

Reduces blood glucose and builds energy stores (anabolic) Polypeptide hormone made in pancreatic beta cells: secretion trigged by metabolism of glucose and ATP production because of glucose oxidation Upregulation of glucose uptake in muscle and adipose Increased glycolysis Increased fatty acid uptake into adipose Increased glycogen synthesis, fatty acid synthesis and protein synthesis

Answer 36

Increases blood glucose and mobilizes energy stores (catabolic) Polypeptide made in pancreatic alpha cells Increased gluconeogenesis in liver Increased glycogenolysis, lipolysis, fatty acid oxidation, proteolysis Does not act on muscle cells

Answer 37

Mobilize energy for muscle activity "Fight or flight" response Amino acid derivatives Increased gluconeogenesis in liver Increased glycogenolysis, lipolysis, fatty acid oxidation and proteolysis

Answer 38

Produce insulin and glucagon | Pancreas in an endocrine organ and an exocrine organ

Answer 39

Insulin levels rise quickly after a meal and glucagon levels decrease quickly after a meal Glucose stimulates insulin secretion Glucose and insulin inhibit glucagon secretion

Answer 40

Produce insulin Pancreas Contain glucokinase (also in liver): isoform of hexokinase

Answer 41

In liver and beta cells of pancreas Isoform of hexokinase Acts as glucose sensor: activity is dependent on glucose concentration over a wide range Does not react with other monosaccharides ie. fructose does not cause insulin secretion

Answer 42

Promote glucose transport into cells Stimulates glycogen synthesis Suppresses glycogen breakdown

Answer 43

Activates extracellular lipoprotein lipase Increases level of acetyl-CoA carboxylase Stimulates triacylglycerol synthesis Suppresses lipolysis

Answer 44

Promotes glycogen synthesis Promotes triacylglycerol synthesis Suppressed gluconeogenesis

Answer 45

Takes up glucose

Answer 46

Only GLUT transporter unregulated by insulin In muscle and adipose Expression and localization regulated by insulin: causes translocation into membrane Other isoforms are present in liver, pancreatic cells, brain, but are not regulated by insulin

Answer 47

Activated by insulin causing increased uptake of fatty acids Storage of dietary or liver-derived fat in adipocytes by hydrolysis of TG into lipoproteins and uptake of fatty acids for resynthesis to TG Fatty acids are activated wth CoA to be esterified with glycerol-3-phoshate

Answer 48

Glycogen synthesis pathway Upregulated by insulin Down regulated by glucagon

Answer 49

Fatty acid synthesis pathway Upregulated by insulin Down regulated by glucagon Inactive by phosphorylation

Answer 50

Glycogenolysis pathway Down regulated by insulin Upregulated by glucagon Inactive by phosphorylation

Answer 51

Adipocyte lipolysis pathway Down regulated by insulin Upregulated by glucagon Activated by phosphorylation

Answer 52

Glycolysis pathway Upregulated by insulin and down regulated by glucagon Inactive by phosphorylation

Answer 53

Receptor tyrosine kinase | Insulin signalling activates several phosphatases

Answer 54

GPCR 1. Binding 2. Activation of receptor 3. Activation of G protein 4. Activation of adenylate cyclase 5. Production of cAMP 6. Activation of PKA 7. Downstream activation of other protein kinases

Answer 55

Activated by phosphorylation by phosphorylase kinase: promoted by glucagon and EN signalling Deactivated by phosphoprotein kinase, which is promoted by insulin

Answer 56

Inhibited by insulin

Answer 57

Activated by insulin

Answer 58

Destruction of beta cells: total loss of insulin production Beta cell destruction is often autoimmune response Treatment by giving insulin Untreated Type 1: ketoacidosis can develop

Answer 59

Insulin signalling is less sensitive than normal, causing insulin resistance Insulin levels are normal or even increased Strongly linked to obesity Can be treated with some oral drugs that increase insulin sensitivity and lifestyle changes AMPK activators promote insulin sensitivity

Answer 60

Nerve and kidney damage Risk of cataract formation Possible mechanisms: glucose can react with proteins, protein modification impairs function Glucose converted to sorbitol when glucose concentrations are very high: increases osmotic pressure

Answer 61

Increased circulating triacylglycerol levels: lipoprotein lipase is not activated Increased fatty acid levels linked to cardiovascular disease

Answer 62

Caused by long-term positive energy balance Caused by inheritance and lifestyle Genetics, environment, epigenetics/microbiome

Answer 63

``` Leptin Leptin receptor Melanocortin receptor Neuropeptide Y receptor Uncoupling protein Susceptibility genes ```

Answer 64

Availability of food High-calorie food Larger portion size Lack of physical activity

Answer 65

Micro biome and perinatal influences

Answer 66

Hormone secreted from adipose tissue to regulate long-term energy storage Signals satiety Deficiency or impaired signalling can cause obesity: human obesity is often associated with leptin resistance

Answer 67

Hormone secreted from adipose tissue to regulate long-term energy storage Activated AMPK to promote fuel catabolism

Answer 68

1. Uncontrolled growth: high proliferation, high need for synthesis of DNA, lipids, proteins 2. Growth without attachment: metastasis, growth of solid tutors instead of monolayers, inside of tumour can become hypoxic 3. Growth without external growth factors: changes in signal transduction, mutations, escaping normal regulation mechanisms 4. Dedifferentiation: support of unlimited growth

Answer 69

PET visualized the body metabolic activity following injection of 2-deoxy-2-fluoroglucose (fluorodeoxyglucose) Deoxyglucose is phosphorylated by hexokinase but not further protein down, and accumulates in cell Dark areas indicate tissues that take up a lot of glucose

Answer 70

1920s Cancer cells generate high levels of ATP through glycolysis and lactate production even when sufficient oxygen is present Mitochondria in cancer cells are dysfunctional: not generally confirmed Later research confirmed that most cancer cells have very high rates of glycolysis even in presence of oxygen: various reasons

Answer 71

More ATP production, synthesis of lipids, nucleotides and proteins High requirement of NADPH and antioxidants Metabolic adaptations in different cancers are highly diverse and depend on original cell type

Answer 72

Less efficient way to generate ATP, but occurs even in presence of oxygen Glycolytic intermediates and pyruvate are diverted into biosynthesis reactions

Answer 73

Major fuel after glucose for cancer cells Anapldrotic reaction to glutamate and alpha-ketoglutarate Can be fully oxidized when malic enzyme is active

Answer 74

Affect cancer cells more than normal cells

Answer 75

Decreased use of glycolytic intermediates in synthesis | Some cancer cells become dependent on extracellular serine when PKM2 is activated

Answer 76

Inhibits pyruvate dehydrogenase kinase | Activated pyruvate dehydrogenase: pyruvate is oxidized an not used in synthetic reactions

Answer 77

Targeting glutamine addiction of cancer cells