Metabolism: an intro Flashcards

1
Q

What is metabolism?

A

Collection of reactions that require reactants and produce products that provide a basis for life

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2
Q

What things affect metabolism?

A
  • part of organism- in multicellular org we have compartmentalisation- so different parts of cell undergo different
    metabolic reaction - cell type
  • nutritional status
  • developmental stage/ age
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3
Q

Why are there some general common principles that govern metabolism?

A
  • common evolutionary origin

- All same laws of thermodynamics

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4
Q

What are metabolic pathways

A

Series of enzymatic reactions that produce specific products- branches and interconnected

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5
Q

What are metabolites

A

reactants, intermediates and products

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6
Q

Why are enzymes needed?

A
  • Complete reactions in a timely fashion
  • Add specificity to reactions (specific complementary active site)
  • Allow regulation of pathways- inhibition
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7
Q

Catabolic vs anabolic reactions- which requires energy?

A
  • Can be catabolic (break down) to make simpler molecules and harness free energy released- harnessed in ATP and NADPH
  • Catabolic reactions are exothermic (release more energy from making than used by breaking bonds)
  • Anabolic- often oxidise the coenzymes (take electrons) onto simple constituents as being built up into more complex compound - require input of free energy- break apart ATP
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8
Q

Outline degradative and biosynthetic pathways

A

Degradative- often converge on common intermediate e.g. acetyl CoA or pyruvate, further metabolised in Krebs/TCA cycle
-Biosynthetic pathways- few metabolites are the starting point- making many products

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9
Q

Outline where some important reactions in metabolism occur (compartmentalisation)?

A
  • Cytosol- glycolysis, pentose phosphate pathway, fatty acid biosynthesis, many gluconeogenesis reactions
  • mitochondrion- citric acid cycle, ETC and oxidative phosphorylation, fatty acid oxidation, amino acid breakdown
    Transport systems to move around intermediates
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10
Q

What is the metabolic flux?

A

Metabolic flux: Direction of gross mass flow of metabolites through a pathway

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11
Q

How do cells control flux

A

Normally through slowest RDS (with most -ve delta G)

  • Short term strategies- allosteric control (coenzymes, reactants, products)- alter structure turning on/off
  • Long term control- covalent modification- prosthetic groups , phosphate added (subject to hormonal control), genetic control- change transcription so less/more mRNA produced, reciprocal control varying rates of 2 opposing non-equilibrium reactions
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12
Q

How much energy is recommended/ do we get from each source?

A
  • 2000-3000kcal/day
  • Carb and protein 4kcal/g
  • Lipid 9kcal/g
  • 30% fat 15% protein 55% carb
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13
Q

Digestion of carbohydrates

A
  • majority in diet = polysaccharides
  • salivary amylase in mouth to oligosaccharides (tri/disaccharides)
  • acidic stomach- stopping action salivary amylase
  • Pancreatic amylase- released into small intestine for further digestion
  • Final digestion of disaccharides to monosaccharides by enzymes on mucosal cells
  • In duodenum glucose taken up by Na transporters in active transport - Found on the brush border of epithelial cells= moved into circulatory system
  • Via portal circulation flushed through liver- role in detoxification
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14
Q

Explain some properties of glucose

A
- Most abundant carbohydrate 
C6H12O6
L and D enantiomers (stereoisomers)
Humans stored as insoluble glycogen, in plants as starch 
Comes from diet or body stores 
a and b form (ABBA)
In solution- not linear forms 6 membered ring- pyranose 
5 C rings are called furanose
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15
Q

How are glucose levels controlled?

A
  • major carb transported in blood
  • Levels controlled by hormones secreted by pancreas (insulin and glucagon)
    Ideal conc 5mM
    Required by brain (preferred substrate) and erythrocytes
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16
Q

What are the 2 steps of glycolysis

A

1) Energy investment phase- phosphorylated forms created using ATP- don’t easily cross membrane keeping it in the cytosol
2) Energy generation phase- creating ATP

17
Q

How does glucose enter cells?

A

1) Na- independent facilitated diffusion transport- via GLUT proteins (1-14), tissue specific expression e.g. GLUT 4 in muscle
2) ATP- dependent Na+ - monosaccharide transport- glucose co-transported with Na against conc gradient- in intestinal epithelial cells- often after meal so high blood [glucose]

18
Q

Outline glycolysis

A

See pic

19
Q

In which steps is ATP required

A
  • glucose–> glucose 6- phosphate

- Fructose 6- phosphate–> fructose 1,6-bisphosphate

20
Q

In which step is ATP produced? What is this called?

A
  • 1,3-biphosphoglycerate–> 3 phosphoglycerate 2ATP
  • phosphoenolpyruvate–> pyruvate 2ATP
  • substrate level phosphorylation
21
Q

Which step requires NAD?

A

Glyceraldehyde 3-P–> 1,3- diphosphoglycerate

22
Q

When is water produced

A

2-Phosphoglycerate–> phosphoenolpyruvate via enolase

23
Q

3 important control points

A

3 irreversible reactions

  • glucose to glucose 6P
  • Fructose 6P to fructose 1,6- biphosphate
  • phosphenolpyruvate to pyruvate
24
Q

Explain in further detail control point between fructose 6P and fructose 1,6- biphosphate

A

3) Phosphorylation
- Important control point- irreversible and rate limiting
- Controlled by [ATP]- high= inhibition as abundance of energy low= activation- as running out energy
- Also [fructose 6-phosphate]
- Inhibited by citrate- TCA intermediate- produced by downstream set of reactions- favours glycogen synthesis

25
Q

Yield of anaerobic VS aerobic conditions

A
  • anaerobic= 2

- aerobic= 8 (6 extra from 2 NADH in oxidative phosphorylation)

26
Q

What is haemolytic anaemia?

A
  • mature RBC lack mitochondria so dependent on glycolysis for ATP production, which are needed to fuel ion pumps to maintain osmosis for correct RBC shape
  • defects in glyosidic enzymes (most common last enzyme pyruvate kinase)- lack ATP- change in RBC shape hence phagocytosis leading to anaemia
  • Regular transfusions required
27
Q

Why might being heterozygous for pyruvate kinase be advantageous

A
  • certain no. malformed RBC- can be advantageous as Plasmodium (parasite for malaria) has difficulty surviving