Metabolism Flashcards

Question

What is the kreb’s cycle inhibited by

Answer 1

Mitochondrial matrix

Answer 2

Acetyl-CoA Citrate Isocitrate Alpha-ketoglutarate Succinylcholine-CoA Succinct Fumarate Maleate Oxaloacetate

Answer 3

Isocitrate dehydrogenase

Answer 4

Citrate synthase Aconitase Isocitrate dehydrogenase Alpha-ketoglutarate dehydrogenase Succinyl-CoA synthase Succinct dehydrogenase Fumarate hydratase (fumarase) Maleate dehydrogenase

Answer 5

2 ATP directly (4 ATP made and 2 ATP used) 6 ATP produced by 2NADH2 (3 each)

Answer 6

9 ATP produced by 3 NADH2 (3 each) 2 ATP produced by FADH2 (2 each)

Answer 7

Sum of chemical reactions that occur within each cell of an organism

Answer 8

Forming large molecules from small molecules, requires energy

Answer 9

Breaking down large molecules into smaller ones, creates energy

Answer 10

56 7 kcal/g x 8g (10ml=1unit) = 56 kcal/unit

Answer 11

Energy required to maintain non-exercise bodily functions (homeostasis)

Answer 12

Kcal expended/hr/m^2

Answer 13

Estimates BMR based on age, weight and gender

Answer 14

Male (increased muscle mass) Regular exercise Caffeine Young age (growing) Temperature extreme Disease Hyperthyroidism Pregnancy and lactation Infection and chronic disease

Answer 15

Starvation/ dieting Old age (decreased muscle mass) Hypothyroidism

Answer 16

Weight (kg)/ height (m^2)

Answer 17

When awake, rested and fasted for 12hrs

Answer 18

• biosynthetic • fuel storage • oxidative processes • waste disposal

Answer 19

linoleic (omega 6) and alpha-linolenic (omega 3) series

Answer 20

lysine, isoleucine, leucine, threonine, valine, tryptophan, phenylalanine, methionine, and histidine.

Answer 21

Glyceraldehyde-3-phosphate Dihydroxyacetone phosphate

Answer 22

Phosphofructokinase

Answer 23

3 fatty acids esterified to one glycerol moiety (group)

Answer 24

25-35 kcal/day/kg

Answer 25

fuels, essential amino acids, essential fatty acids, vitamins, minerals, water, xerobiotics (foreign substances eg drugs)

Answer 26

adipose tissue (only 15% water) as triglycerides (for 70kg man approx. 15kg)

Answer 27

glycogen in liver (for 70kg man up to 200g) and muscles (70kg man- 150g)

Answer 28

muscle (80% water) (for 70kg man approx. 6kg)

Answer 29

1 kcal/kg body mass/hour

Answer 30

Amount of metabolically active tissue (including the major organs) and the lean (or fat free) body mass

Answer 31

CO2 produced

Answer 32

• post-absorptive (12 hour fast) • lying still at physical and mental rest • Thermo-neutral environment ( 27 -29°C) • No tea/coffee/nicotine/alcohol in previous 12 hours • no heavy physical activity in previous 24 hours • establish steady state (30 mins)

Answer 33

Greater proportion of metabolically active tissue

Answer 34

More adipose tissue and less muscle mass

Answer 35

30% higher than basal metabolic weight for a very sedentary person and a value of 60% to 70% of the BMR (per day) for a person who engages in about 2 hours of moderate physical activity per day A value of 100% or more of the BMR is used for a person who does several hours of vigorous physical activity per day.

Answer 36

a state of nutrition with a deficiency, excess or imbalance of energy, protein or other nutrients, causing measure adverse effects on tissue/body shape/size/composition, body function and clinical outcome

Answer 37

• Overnight fast - decreases insulin secretion → glycogenolysis (break down glycogen to produce glucose) Brain requires approx 150g glucose/day. After an overnight fast, liver has about 80g glycogen • Longer fasts necessitate gluconeogenesis (uses lactate, amino acids (muscle, intestine, skin breakdown) and glycerol (fat breakdown))- decrease insulin secretion and increased cortisol secretion - lipolysis and proteolysis • >4 days- liver creates ketones from fatty acids, brain adapts to using ketones (ketones are acidic so excess causes blood pH to fall- ketoacidosis- prevent enzyme function), BMR falls (accommodation)

Answer 38

Daily energy expenditure

Answer 39

CO2, H2O, NH4+

Answer 40

more reduced so can oxidise more to produce more energy

Answer 41

Calciferol

Answer 42

Tocopherol

Answer 43

Phylloquinone, Menaphthone

Answer 44

Ascorbic acid

Answer 45

Riboflavin

Answer 46

B1, B2, B3, pantothenic acid, B6, biotin, folate, B12

Answer 47

ascorbic acid, fruit and vegetables, heat labile, collagen synthesis, improve iron absorption, antioxidant Destroyed by heat Lack of vitamin C = Scurvy

Answer 48

cobalamin, protein synthesis, DNA synthesis, regenerate folate, fatty acid synthesis, energy production Broken down in stomach with cofactor Absorbed in terminal ileum

Answer 49

glycogen to sustain energy levels for 12 hours

Answer 50

provide energy for up to 12 weeks

Answer 51

used when muscle glycogen stores fail

Answer 52

• 5+ servings of fruit/vegetables • Base meals around starchy (complex) carbohydrates • No more than 5% energy should come from free sugars (glucose, fructose) • 0.8 g/kg/day protein • Saturated fat: no more than 30g/day for men & 20g/day for women • No more than 2.4g/day of sodium (6g salt) • No more than 14 units alcohol / week (over at least 3 days) • Adequate calcium

Answer 53

0.8g/kg/day

Answer 54

2.4 g/day (6g salt)

Answer 55

No more than 30g per day for men No more than 20g per day for women

Answer 56

No more than 5%

Answer 57

Sodium Potassium Calcium Chloride Phosphorus Magnesium

Answer 58

Moves phosphate group

Answer 59

currency of metabolic energy- a high energy molecule composed of adenine, ribose and 3 phosphate groups Hydrolysis of ATP to ADP and Pi energy is stored in phosphate bonds

Answer 60

• emergency energy producing pathway when oxygen is limiting (erythrocytes and exercising skeletal muscle) • Generates precursors for biosynthesis: • Glucose-6-Phosphate converted to ribose-5-P (nucleotides) via pentose phosphate pathway and G-1-P for glycogen synthesis • Pyruvate- transaminated to alanine, substrate for fatty acid synthesis • Glycerol-3-P is backbone of triglycerides

Answer 61

Hexokinase using ATP

Answer 62

Phosphoglucose isomerase

Answer 63

Phosphofructokinase-1 using ATP

Answer 64

Triose phosphate isomerase

Answer 65

Triose phosphate dehydrogenase

Answer 66

2 molecules of NADH

Answer 67

Glucose —> glucose-6-phosphate Fructose-6-phosphate —> fructose-1,6-bisphosphate

Answer 68

Phosphoglycerokinase

Answer 69

Phosphoglyceromutase

Answer 70

Pyruvate kinase

Answer 71

1,3-bisphosphoglycerate —> 3-phosphoglycerate Phosphoenolpyruvate—> Pyruvate

Answer 72

Substrate level phosphorylation

Answer 73

Glucose —>glucose-6-phosphate Fructose-6-phosphate —>fructose-1,6-bisphosphate Phosphoenolpyruvate—> pyruvate

Answer 74

molecule binds to a non-catalytic site, conformational change which changes affinity for the substrate

Answer 75

PFK1 (Reduces energy wastage)

Answer 76

activator of PFK1, when ATP is used up, ADP accumulates and is converted to AMP by adenylate kinase reaction to generate ATP 2ADP = ATP + AMP

Answer 77

inhibits PFK1 so a signal cycle does not need more fuel

Answer 78

generates from fructose-6-phosphate, inhibitor of PFK1, mediates effect of insulin and glucagon

Answer 79

Inhibits PFK1

Answer 80

insulin and glucagon. Indirect route through affecting regulatory molecules (eg kinases or phosphatases) Increases or decreases gene expression for the enzyme Increase or decrease enzyme activity

Answer 81

lactate formation catalysed by lactate dehydrogenase. Regeneration of NAD+ by oxidation Important to allow glycolysis to continue so it can produce one ATP in low O2 conditions or erythrocytes Glucose + 2ADP + 2Pi → 2 lactate + 2 ATP + 2H2O + 2H+

Answer 82

prevent build up of lactic acid and muscle fatigue

Answer 83

In liver, gluconeogenesis of lactate to glucose through lactate dehydrogenase In hepatocytes

Answer 84

enters mictochondria and converted to Acetyl CoA and CO2 by pyruvate dehydrogenase in a decarboxylation reaction (link reaction). Acetyl CoA can enter Kreb’s cycle for more energy production . Inhibited allosterically by its products Acetyl CoA, ATP and NADH when in high concentrations, and products indirectly act by activating a kinase that phosphorylates and inhibits PDH Decarboxylation of pyruvate to Acetyl-CoA is irreversible Pyruvate + CoA + NAD+ → Acetyl-CoA + CO2 + NADH + H+

Answer 85

Pyruvate dehydrogenase

Answer 86

allosterically by its products Acetyl CoA, ATP and NADH when in high concentrations, and products indirectly act by activating a kinase that phosphorylates and inhibits PDH

Answer 87

Sparse capillaries Sparse mitochondria Sparse myoglobin Low oxidative capacity/ high glycolytic Easily fatigued High ATPase activity Fast contractions

Answer 88

Abundant capillaries Abundant mitochondria Abundant myoglobin High oxidative capacity Fatigue resistant Low ATPase activity Slow contractions

Answer 89

• Generates lots of energy in form of ATP • provides final common pathway for oxidation of carbohydrates, fat and protein via Acetyl CoA • produces intermediates for the synthesis of amino acids, glucose, heme etc • Sequence of 8 enzymatic reactions • Acetyl CoA condenses oxaloacetate forming citrate • Oxaloacetate is regenerated in the last step of the krebs’ cycle and 2 CO2 molecules released • Energy is harvested in the form of NADH, 2FADH2 and ATP molecules

Answer 90

Citrate Is Krebs’ Starting Substrate For Making Oxaloacetate

Answer 91

Citrate synthase

Answer 92

Isocitrate dehydrogenase

Answer 93

CO2 and NADH

Answer 94

Alpha-ketoglutarate dehydrogenase

Answer 95

CO2 and NADH

Answer 96

Succinate thiokinase

Answer 97

Phosphorylation of GDP to GTP which is then converted to ATP

Answer 98

Succinate dehydrogenase

Answer 99

Fumarate hydrase (by addition of water)

Answer 100

Malate dehydrogenase

Answer 101

• rate determined by levels of ATP, NADH, FADH2- high levels inhibit Krebs’ cycle • Activated by high ADP • Alpha-ketoglutarate dehydrogenase as activated by Ca2+ (muscle contraction) • if cycle inhibited, build up of Acetyl CoA so undergoes fatty acid synthesis

Answer 102

ATP, NADH, Acetyl-CoA

Answer 103

ATP, NADH, citrate

Answer 104

ATP, NADH, GTP, succinyl-CoA

Answer 105

occurs in inner mitochondrial membrane, aerobic conditions

Answer 106

1. Components of ETC accept electrons (reduced) and pass them on (oxidised). 2. Electrons are transferred to final electron acceptor O2 (which is reduced by hydrogen to form water) 3. Free energy drop as electrons are passed down ETC 4. Free energy is used to pump H+ across the inner membrane space via the Cytochrome-C oxidase complex, creating a proton motive gradient 5. ATP synthase contains a proton pore 6. ATP produced as protons flux in through ATP synthase- energy coupled to chemiosmosis (about 28 ATP molecules) 7. In the matrix, the H+, electrons and oxygen combine to form water as O2 is the final electron acceptor 1/2O2 + 2e- + 2H+ → H2O

Answer 107

Removes electrons from NADH

Answer 108

Removes electrons from FADH2 in prescence of coenzyme Q (ubiquinone)

Answer 109

donate electrons to cytochromes containing iron (anemia and OXPHOS diseases decreases mitochondrial capacity for oxidative phosphorylation)

Answer 110

Inner mitochondrial membrane is impermeable

Answer 111

Proton leakage, chemical uncouplers and regular uncoupling protons

Answer 112

rate of ATP synthesis by the transmembrane electrochemical gradient As ATP is used for energy-requiring processes and ADP levels increase, proton influx through the ATP synthase pore generates more ATP, and the electron transport chain responds to restore Δp. In uncoupling, protons return to the matrix by a mechanism that bypasses the ATP synthase pore, and the energy is released as heat.

Answer 113

balance ATP generation

Answer 114

• Low glucose is damaging to cells/brain • High glucose is damaging (glycosylation of proteins) • Maintained through action of anabolic hormones (insulin) and catabolic hormones (glucagon, catecholamines)

Answer 115

4.5-5.5 mmol/L

Answer 116

Acetone Acetoacetone Beta-hydroxybutyrate

Answer 117

• occurs when high ATP levels which inhibits the Krebs’ cycle and was to a build up Acetyl CoA • Occurs in cytosol of cell • But Acetyl CoA cannot cross mitochondrial membrane

Answer 118

• carboxylic head group with aliphatic tail • Long acyl CoA chains • saturated and unsaturated • most are derived from triglycerides and phospholipids

Answer 119

Linoleic acid Oleic acid

Answer 120

Palmitic acid

Answer 121

Arachidonic acid

Answer 122

1. Bile salts emulsify dietary fats in small intestine, forming mixed micelles 2. Intestinal lipases degrade triacylglycerols 3. Fatty acids and other breakdown products are taken up by the intestinal mucosa and converted into triacylglycerols 4. Triacylglycerols are incorporated with cholesterol and apoproteins into chylomicrons 5. Chylomicrons move through the lymphatic system and bloodstream to tissues 6. Lipoprotein lipase, activated by apoC-II in the capillary, releases fatty acids and glycerol 7. Fatty acids enter cell 8. Oxidised as fuel or reesterified for storage

Answer 123

apoC-II in the capillary

Answer 124

Triacylglyerols Cholesterol Apoproteins

Answer 125

• must be activated in the cytoplasm before they can be oxidised in the mitochondria • if the acyl-CoA has < 12 carbons - can diffuse through mitochondrial membrane • most dietary fatty acids have > 14 carbons - taken through mitochondrial membrane using the carnitine shuttle Fatty acid → acyl adenylate → acyl CoA ATP -> PPi. HS-CoA -> AMP

Answer 126

Fatty acid → acyl adenylate → acyl CoA

Answer 127

Acyl-CoA synthase

Answer 128

• oxaloacetate bonds with Acetyl CoA to produce citrate- can cross mitochondrial membrane into cytosol • Citrate ligase converts citrate back to oxaloacetate which is then broken down into pyruvate and Acetyl CoA • Pyruvate recycled back into mitochondria and converted to oxaloacetate so can re-enter Krebs’ cycle • Acetyl-CoA converted into fatty acids

Answer 129

• the acyl-CoA chains are converted and reformed in order to cross the membrane • Acyl-CoA to acyl carnitine by carnitine acyltransferase 1 (CAT1)- Located on outer mitochondrial membrane • CoA is recycled • acyl carnitine is reformed to acyl CoA by cartinine acyltransferase 2 (CAT2)- On interior of membrane • Cartinine recycled through the outer membrane

Answer 130

Energy derived from fatty acid beta-oxidation • once acyl-CoA has crossed the membrane it can now be oxidised • This involves the sequential removal of 2 carbon units by oxidation- the second (hence beta) carbon is cleaves • Each round produces 1 NADH, 1 FADH2, and 1 Acetyl-CoA • FADH2 and NAD undergo oxidative phosphorylation • Acetyl-CoA re-enters the krebs’ cycle • ATP is produced • Oxidation →hydration →oxidation →thiolysis

Answer 131

Occurs in response to decreased blood glucose and high glucagon

Answer 132

Acyl-CoA —> Acetyl-CoA Following oxidation -> hydration-> oxidation ->thiolysis

Answer 133

Acyl-CoA dehydrogenase

Answer 134

Enol-CoA hydrase

Answer 135

Hydroxyacyl CoA- dehydrogenase

Answer 136

1 NADH 1 FADH2 1 Acetyl-CoA

Answer 137

• under normal metabolic conditions most Acetyl-CoA is utilised via the TCA acid cycle to produce glucose • A small proportion is converted to ketones • Ketones- molecules produced by the liver from Acetyl-CoA - have a characteristic fruity/nail polish remover-like smell • during high rates of fatty acid oxidation, large amounts of Acetyl-CoA are generated • this exceeds the capacity of the krebs' cycle, which results in ketogenesis

Answer 138

molecules produced by the liver from Acetyl-CoA - have a characteristic fruity (pear drops)/nail polish remover-like smell

Answer 139

hyperventilation in response to hypoxia

Answer 140

renal failure, loss of HCO3-, excess H+ production

Answer 141

PaCO2 increases leading to an increase in H+ ions and so pH decreases • CO2 production is greater than CO2 elimination

Answer 142

• acetoacetate can undergo spontaneous decorboxylation to acetone, or be enzymatically converted to beta-hydroxybutyrate • ketone bodies utilised by extrahepatic tissues through conversion of beta-hydroxybutyrate and acetoacetate to acetoacetyl-CoA • this requires the enzyme acetoacetate: succinyl-CoA transferase, which is found in all but hepatic tissue • When glycogen levels in liver are high, beta-hydroxybutyrate production increases

Answer 143

2 acetyl-CoA —> acetoacetyl CoA—> 3-hydroxy-3-methyl glutaryl CoA (HMG CoA)—> acetoacetate —> EITHER alpha-beta-hydroxybutyrate OR acetone

Answer 144

HMG CoA synthase

Answer 145

HMG CoA lysase

Answer 146

Alpha-beta-hydroxybutyrate dehydrogenase

Answer 147

NONE it occurs spontaneously

Answer 148

• release of free fatty acids from adipose tissue- more fatty acids, more ketones • a high concentration of glycerol-3-phosphate in the liver results in triglyceride production, whilst a low level results in increased ketone body production • when demand for ATP is high, Acetyl-CoA is likely to be further oxidised via the TCA cycle to CO2 • fat oxidation is dependent upon the amount of glucagon (activation) or insulin (inhibition) present

Answer 149

• during normal physiological conditions the production of ketones occurs at a low rate • carbohydrate shortages cause the liver to increase ketone the body production from Acetyl-CoA • the heart and skeletal muscles preferentially utilise ketone bodies for energy preserving glucose for the brain

Answer 150

• occurs in insulin-dependent diabetics when dose is inadequate or because of increased insulin requirement (infection, trauma, acute illness) • often the presenting feature in newly diagnosed type 1 diabetics • also occurs in chronic alcohol abuse and starvation • patients present with hyperventilation and vomiting

Answer 151

ketones are relatively strong acids (pKa~ 3.5). Excessive ketones lower blood pH which impairs ability of haemoglobin to bind to oxygen

Answer 152

pH- low pO2- high pCO2- low HCO3- low CO2 low as acidic so hyperventilate to remove CO2 from blood to compensate for acidic ketones and lots of O2 HCO3 bicarbonate (base) trying to neutralise blood so low levels left

Answer 153

Insulin deficiency: 1. Inhibition of glycolysis and stimulation of glyconeogenesis 2. Glycogen breakdown and inhibition of glycogen synthesis 3. Increased lipolysis (increased free fatty acids) -1 and 2 lead to hyperglycaemia -3 leads to Increased acetoacetate and beta-hydroxybutyrate (Can be oxidised as fuels in most tissues (eg skeletal muscle))

Answer 154

• sliding scale of insulin • IV fluid hydration (10% dextrose and 0.9% saline) • monitor fluid balance closely • 40 mmol potassium • pabrinex: injection containing vitamins C, B1, B2, B3, B6

Answer 155

High blood EtOH concentration Depleted protein and carbohydrate stores: 1. Impaired gluconeogenesis 2. Decreased insulin and increased glucagon secretion Increased lipolysis (increased free fatty acids) Increased ketone production

Answer 156

Protein Haemoglobin Bicarbonate

Answer 157

Maintenance of a stable internal environment eg temperature, glucose, potassium, blood oxygen, hydrogen ions

Answer 158

Ductless Release hormones into blood

Answer 159

messenger molecules bind with receptors in cell where they are produced eg chemical/secondary messengers

Answer 160

messengers in ECF eg clotting factors, prostaglandins in childbirth, inflammatory mediators, interleukins signalling in immune system mainly between white blood cells, platelet derived growth factor releases from platelets and regulates cell growth. Signal diffuses across gap between cells. Inactivated locally so doesn’t enter blood stream

Answer 161

secretions into blood eg insulin

Answer 162

secrete substances through ducts onto your body surfaces. Exocrine glands secrete sweat, tears, saliva, milk and digestive juices

Answer 163

hypothalamus, pituitary, thyroid, adrenals, pancreas, ovaries, testes, skin, heart

Answer 164

Made of short amino acid chains (some have carbohydrate side chains- glycoproteins) Hydrophilic so can dissolve in blood Stored in cell and released when needed/signalled Binds to a receptor on membrane Produces a quick response via a secondary messenger cascade (eg cAMP, Ca2+) Eg insulin, growth hormone, TSH and ADH

Answer 165

Synthesised from tyrosine Acts in same way as peptide hormones Eg adrenaline (epinephrine), thyroid hormones (T4 and T3)

Answer 166

Synthesised from cholesterol Water insoluble and lipid soluble- can cross membranes but requires transport proteins in blood Intercellular receptor target Synthesised on demand Steroid hormone made in cell and diffuses out once made (not stored) Directly affects DNA and alters transcription/translation- slow response as proteins have to be made Eg testosterones, oestrogen, cortisol

Answer 167

Albumin Sex hormone binding globulin

Answer 168

Cholesterol

Answer 169

signal is amplified • when a deviation from an optimum causes changes that results in an even greater deviation from the normal e.g. During birth oxytocin released due to increased pressure, which causes more contractions, increasing pressure, releasing more oxytocin; action potentials; bone repair (osteocalcin) or hypothermia/hyperthermia

Answer 170

when the change produced by the control system leads to a change in the stimulus detected by the receptor and turns the system off (system is restored to its original level) • eg blood glucose

Answer 171

Beta oxidation is used in aerobic conditions as fuel when there is increased demand e.g. during fasting or states of low blood glucose. However it cannot be used as fuel for the nervous system because fatty acids cannot pass the blood-brain barrier