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Flashcards in MCB: Getting energy from carbohydrates Deck (16):
1

What is the insulin receptor?

Tyrosine kinase receptor

Autophosphorylation catalyses phosphorylation of cellular proteins (IRS family, Shc and Cbl) and diverse pathway activation (PI(3)K, Ras and TC10)

Pathways act in concerted fashion to coordinate regulation of vesicle trafficking, synthesis, enzyme activation and inactivation, gene expression → results in regulation of glucose, lipid and protein metabolism

2

Outline respiration (brief)

Oxidation of fuels → ATP
Glucose, fatty acids, amino acids are oxidised to acetyl CoA which enters the TCA cycle for complete oxidation to CO2

As fuels are oxidised, electrons are transferred to O2 via the electron transport chain → water; this energy is used to generate ATP

3

Outline glycolysis (general facts)

First stage of glucose oxidation (carbohydrate catabolism)
Cytosolic

Aerobic (presence of O2, tissues with mitochondria):
- 36 moles of ATP per mole of glucose (after TCA and ETC)
- cannot occur in rbcs as they have no mitochondria - needed for the entry of pyruvate

Anaerobic:
-ancient metabolic pathway, probably 3.5 billion years ago when no available oxygen
-occurs in tissues with lack of mitochondria (rbc) or lack of --- oxygen (muscle cells under extreme exertion)
- 2 moles of ATP per glucose molecule

4

Outline the steps in aerobic glycolysis

glucose → glucose-6-phosphate [hexokinase, ATP→ADP]

G6P → fructose-6-phosphate [phosphofructokinase]

F6P → fructose-1,6-bisphosphate [ATP→ADP]

F16BP → 2x phosphoglyceraldhyde (PGA/G3P)

2x PGA/G3P → 2x pyruvate [pyruvate kinase, 4ADP→4ATP, 2NAD⁺ → 2NADH]

Products: 2ATP, 2NADH

5

Outline how pyruvate enters the TCA cycle

Reaction carried out in mitochondria

Pyr + CoA + NAD⁺ → acetyl CoA + CO2 + NADH + H⁺

6

What is NAD

Nicotinamide adenine dinucleotide: NAD⁺

Coenyzme found in all living cells - a dinucleotide (consists of two nucleotides, one containing adenosine ring, one containing nicotinamide)

Involved in redox reactions: carrying electrons from one reaction to another

NAD⁺ = oxidising agent, accepts electrons from other molecules and becomes reduced - forms NADH
NADH can be used as reducing agent to donate electrons

7

Outline the steps in anaerobic glycolysis

glycolysis as normal → 2 pyruvate [2 ATP, 2NADH]

2x pyruvate → 2x lactate [lactate dehydrogenase, 2NADH → 2NAD⁺]

reaction occurs in cytosol

8

Why is lactate dehydrogenase required in anaerobic respiration?

NADH produced during glycolysis must be reoxidised (NAD is needed for the G3P dehydrogenase reaction)

In aerobic, mitochondrially derived oxidising agents do this, but in anaerobic respiration these oxidising agents are absent

Lactate dehydrogenase used to regenerate NAD

9

What is the Cori cycle?

Cycling of lactate that is produced by anaerobic respiration (red blood cells and muscle) back into glucose

Lactate diffuses into the blood and is taken up by liver → converted back to pyruvate [lactate dehydrogenase]

Pyruvate converted → glucose via gluconeogenesis

Glucose released into the blood, used once again for energy by red blood cells and muscle

LIVER: 2xlactate→2xpyruvate→(6ATP used)→glucose
MUSCLE: glucose→2xpyruvate + 2ATP(released)→2xlactate

10

What is the pentose phosphate pathway?

Alternative pathway of glucose metabolism
Does not produce ATP, does not oxidise glucose completely

Versatile: provides raw materials, NADPH and pentose phosphates (5C - synthesis of DNA and RNA), for cellular functions in response to fluctuating need

Cytosolic pathway in all cells
Branches from glycolysis at Glc-6-P (sometimes called the hexose monophosphate shunt)

Shunt: if little requirement for pentoses, PPP intermediates can be recycled into glycolysis by conversion into fruc-6-P or G3P

About 10% of glucose within the rbc is shunted through the PPP, to generate NADPH for the reduction of glutathione: GSSG → GSH (GSH = essential molecule for antioxidant defence)

11

Outline the steps in the pentose phosphate pathway

Irreversible redox/oxidative stage:

Glucose-6-phosphate → gluconate-6-phosphate / 6-phosphogluconate [glucose-6-phosphate dehydrogenase (G6PD), NADP → NADPH]

Gluconate-6-phosphate/6-phosphogluconate → ribulose-5-phosphate [6PGD, NADP⁺ → NADPH]

Reversible non-oxidative/interconversion stage:

Ribulose-5-phosphate (x3) → G3P(PGA) (x1) +fructose-6-phosphate (x2)

12

When do the oxidative/non-oxidative stages of PPP occur? How are they used?

Balanced need for NADPH and pentose phosphates (dividing and synthesising fatty acids in equal measure) - only the irreversible redox stage is required

Ribulose-5-phosphate → isomerised → ribose-5-phosphate (used for synthesised of ribo- and deoxyribo- nucleotides)

If there is more need for NADPH than nucleotide precursors (non-dividing cells), excess pentose phosphates are recycled into glycolysis intermediates → non-oxidative stage

13

Outline the difference between NADH and NADPH

Single phosphate group → no effect on electron carrying capability → distinguishes between two molecules so they can interact with different sets of enzymes

Two different pathways, within the same cell, using electron carriers, can be regulated independently

Cell can have access to both oxidising agents (NAD⁺) and reducing agents (NADPH) for anabolic and catabolic reactions

14

How is NADPH used by red blood cells?

Reduced glutathione (GSH) = tripeptide (glutamate, cysteine, glycine) - scavenger for dangerous oxidative metabolites in cell

Converts H2O2 (harmful) to water

2GSH → GSSG [glutathione peroxidase, H202 → H20]
GSSG → 2GSH [glutathione reductase, NADPH→NADP⁺]

NADPH produced in pentose phosphate pathway is need to produce reduced glutathione from its oxidised form

15

What is hemolytic anaemia?

red blood cells destroyed faster than the bone marrow produces them

glucose-6-phosphate dehydrogenase (G6PD) deficiency

X-linked recessive, more common in malaria areas (as disorder also has insufficient quantities of metabolite for malarial parasite survival)

G6PD; maintains sufficient NADPH levels in cell - mutation changes shape or alters stability - not fully active

Red blood cell deficient in NADPH unable to neutralise H2O2 - strong oxidant, degrades red blood cell and causes hemolysis if it isn't reduced (oxidative stress → denaturation/unfolding haemoglobin molecule → cannot effectively transport oxygen → often destroyed prematurely)

16

How does G6PD deficiency present clinically?

Neonatal jaundice - insufficient enzyme activity in liver

Hemolytic anemia: fatigue, paleness, rapid heart rate, yellow skin colour, dark urine

Oxidative stress - may precipitate after oxidising drugs e.g.: antimalarials, aspirin, fava beans (fauvism)

Treatment depends on cause: discontinue oxidising drugs, change diet, blood transfusion