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1

What is metabolism?

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

2

What things affect metabolism?

- 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

3

Why are there some general common principles that govern metabolism?

- common evolutionary origin
- All same laws of thermodynamics

4

What are metabolic pathways

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

5

What are metabolites

reactants, intermediates and products

6

Why are enzymes needed?

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

7

Catabolic vs anabolic reactions- which requires energy?

- 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

8

Outline degradative and biosynthetic pathways

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

9

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

- 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

10

What is the metabolic flux?

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

11

How do cells control flux

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

12

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

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

13

Digestion of carbohydrates

- 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

14

Explain some properties of glucose

- 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

15

How are glucose levels controlled?

- 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

16

What are the 2 steps of glycolysis

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

How does glucose enter cells?

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

Outline glycolysis

See pic

19

In which steps is ATP required

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

20

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

-1,3-biphosphoglycerate--> 3 phosphoglycerate 2ATP
- phosphoenolpyruvate--> pyruvate 2ATP
- substrate level phosphorylation

21

Which step requires NAD?

Glyceraldehyde 3-P--> 1,3- diphosphoglycerate

22

When is water produced

2-Phosphoglycerate--> phosphoenolpyruvate via enolase

23

3 important control points

3 irreversible reactions
- glucose to glucose 6P
-Fructose 6P to fructose 1,6- biphosphate
-phosphenolpyruvate to pyruvate

24

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

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

Yield of anaerobic VS aerobic conditions

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

26

What is haemolytic anaemia?

- 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

Why might being heterozygous for pyruvate kinase be advantageous

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