8 - Carbohydrates + Glycolysis Flashcards

1
Q

What are two important intermediates from glycolysis?

A

- Glycerol Phosphate (from oxidation of DHAP) - Triglyceride and phospholipid biosynthesis in liver and adipose.

- 2-3 Bisphosphoglycerate (from 1,3 BPG) - Regulator of haemoglobin’s O2 affinity as makes it rigid

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2
Q

Why is lactate dehydrogenase important in RBC?

A

RBC have no mitochondrial stage of metabolism so have no way of oxidising NADH back to NAD to be used for more ATP synthesis. LDH allows NAD to be produced so glycolysis can continue

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3
Q

What is normal lactate production and how can this vary?

A

40 - 50g a day from RBC and skeletal muscle

Can increase when:

— Exercising e.g 30g in 5 mins

— Hearty eating

— Shock

— Congestive Heart Disease

— Thyamine deficiency

— Liver disease

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4
Q

Why would thiamine deficiency lead to lactate acidosis?

A

Thiamine (Vitamin B) is cofactor in converting pyruvate to acetyl coA. If no thiamine, pyruvate converted to lactate instead

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5
Q

How does LDH work?

A

Reduces pyruvate to lactate using NADH which oxidises NADH back to NAD to be used in glycolysis. Allows glycolysis to keep occurring

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6
Q

Explain how LDH works as a cycle?

A
  • Lactate released into blood by muscle and RBC
  • Metabolised by liver and heart
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7
Q

What does plasma lactate concentration depend on?

A
  • Production
  • Utilisation (heart, kidney, lungs)
  • Disposal (kidney)
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8
Q

What is hyperlactaemia and lactic acidosis?

A
  • Normal 1mM/L
  • Hyper is 2-5 mM/L, no change in blood pH as blood buffers it
  • Acidosis is above 5mM/L and blood pH is lowered as above renal threshold to buffer. Sign of critically ill patient
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9
Q

How is fructose (and galactose) metabolised?

A

In liver

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10
Q

What are two issues with fructose metabolism and what are the consequences?

A

- Essential fructosuria: Fructokinase missing so fructose builds up and excreted. No major issue just not efficient metabolism

  • Fructose Intolerance: Aldolase missing. Fructose-1-p build up in liver causes damage. Remove fructose from diet
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11
Q

What is galactosemia?

A

Genetic disorder that prevents metabolism of galactose.

Due to lack of 1 of 3 enzymes:

  • Galactokinase
  • Uridyl transferase
  • UDP-galactose-epimerase
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12
Q

What paths can the metabolism of galactose take?

A

Glycolysis or Glycogenesis

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13
Q

How can galactosemia be caused?

A
  • Galactokinase deficiency (rare) - Galactose accumaltes but just excreted
  • Transferase deficiency (common) - Galactose and galactose 1-p accumulate. Galactose enters other pathways it shouldn’t (galactitol) and uses NADPH so cataracts. Galactose 1-p damages liver, kidney, brain
  • Treatment: No lactose in diet
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14
Q

What are the symptoms of galactosemia and causes of the symptoms?

A
  • Cataracts - Depleted NADPH levels. NADPH usually prevents disulphide bridges forming between proteins, without NADPH aggregates of proteins can form on lens of eye.
  • Glaucoma - Build up of galactose and galactitol causes intra-ocular pressure and can lead to blindness
  • Liver, Heart, Kidney, Brain damage - Accumulation of galactose-1-p
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15
Q

Explain the diagram of all three monosaccharides entering glycolysis.

A
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16
Q

What is the pentose phosphate pathway?

A

1. Oxidative decarboxylation: G-6-P converted to C5 sugar and CO2, producing NADPH for biosynthesis. Uses enzyme G6PDH

2. Rearrangement for glycotic intermediates: 3 unused C5 sugars converted to 2 F-6P and 1 G3P to enter glycolysis

  • No ATP
  • CO2 produced so irreversible
  • Controlled by NADP/NADPH ratio at G6PDH enzyme
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17
Q

What is the point of the pentose phosphate pathway?

A

- NADPH production : Biosynthesis and prevent disulphide bonds forming

- C5 sugars for nucleotide synthesis: Therefore, high activity of cycle in dividing tissues, e.g bone marrow

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18
Q

What happens if you have a G6PDH deficiency?

A

Common inherited defect

  • Haemolytic Anaemia
  • Cataracts
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19
Q

What is the role of NADPH?

A
  • Involved in biosynthesis
  • Keeps SH group of proteins in reduced state, protecting their integrity and therefore activity. Prevents disulphide bonds forming
  • Maintain GSH levels
  • Detoxification reactions
20
Q

What enzyme limits the rate of the pentose phosphate pathway?

A

G6PDH

21
Q

What is haemolytic anaemia?

A

Anaemia - low level of RBC or Hb leading to pallor or weariness

Hameolysis - abnormal breakdown of RBC.

22
Q

What is glutathione? (GSH)

A

Protein that protects cell from oxidative damage by ‘mopping up’ free radicals. Only active when reduced by NADPH

23
Q

How can acute haemolytic episodes happen?

A

When chemicals are in the body that lower NADPH levels, e.g antimalarials, glycosides

24
Q

What are the four stages of catabolism?

A
  1. Extracellular break down
  2. Glycolysis (cytosol)
  3. Kreb’s (TCA) Cycle
  4. Oxidative Phopshorylation
25
Q

What is the general structure of a carbohydrate?

A

(CH2O)n

26
Q

What is the blood glucose level and what tissues are glucose dependent?

A

5mM/L

  • RBC, Neutrophils, Lens of eye, Cells of kidney medulla (40g/day)
  • CNS (can use ketone but prefer glucose) (140g/day)
27
Q

How are carbohydrates digested extracellularly?

A
  • Salivary Amylase (dextrins)
  • Pancreatic Amylase (monosac a1-4)
  • Lactase, Sucrase, Isomaltase (a 1-6 bonds branching)
28
Q

Why can’t cellulose be digested?

A

Don’t have enzymes to break B1-4 bonds in cellulose

29
Q

How are monosaccharides absorbed?

A
30
Q

What are the different Glucose transporters and where are they found?

A
  • Hormonally regulated and uptake glucose by facilitated diffusion

GLUT 1 - Fetal tissues, adult RBC’S, blood-brain barrier

GLUT 2*- Kidney, Liver, pancreatic beta cells, small intestine

GLUT 3 - Neurones, placenta

GLUT 4 *- Adipose tissue, striated muscle

GLUT 5 - Spermatoza and Intestine

* = insulin regulated

31
Q

What is lactose intolerance, what are the symptoms and how can it be treated?

A
32
Q

What are the different ways you can be lactose intolerant?

A
33
Q

What are the functions and features of glycolysis?

A

Functions

- Oxidation of glucose

  • NADH production
  • Synthesis of ATP
  • Produce C6 and C3 intermediates

Features

- Occurs in all tissues cytoplasm

  • Exergonic
  • With LDH, only anaerobic pathway (no O2)
  • Irreversible
  • No loss of CO2
34
Q

Describe the process of glycolysis and the 3 key enzymes/

A

Hexokinase called glucokinase in liver

35
Q

Why are they so many steps in glycolysis?

A
36
Q

What happens in phase 1 of glycolysis?

A
  • 2ATP required
  • Committing step
37
Q

What happens in phase 2 of glycolysis?

A
38
Q

What is a clinical application of glycolysis?

A

Diagnose cancer

  • Feed patient with radioactive glucose 18 FDFG (hexokinase substrate)
  • Highly metabolic cells (cancer) will uptake the glucose and phosphorylate it but then it cannot be passed through glycolysis as not complementary to enzymes
  • Use PET to image and see where radioactivity is, this will show you where cancer is
39
Q

What are some signs and symptoms of galactosemia?

A
  • Cataracts
  • Renal failure
  • Seizure and brain damage
  • Cirrhosis
  • Hypoglycaemia
40
Q

Why can galactosemia cause cataracts?

A
  • NADPH used to make catalase and gluathione
  • These protect from oxidative stress so if not produced can cause electrons to be taken from thiols
  • Inappropriate disulphide bridges form causing misfolding and crosslinking
  • Denatured crystallin protein is insoluble
41
Q

How is galactose and lactose formed from glucose?

A
42
Q

How could you determine whether someone with galactosemia has a missing enzyme or a or defective enzyme?

A
  • Blood test
  • Enzyme assay
43
Q

Why might someone have fructose or galactose in their urine?

A

Levels in blood above renal threshold

44
Q

Why can someone with galactosemia become jaundiced?

A
  • Liver damage due to build up of glycerate-1-p
  • Liver cannot conjugate bilirubin with glucaronic acid to soluble for so build up in the blood
45
Q

Would a mother who is galactosemic be able to produce lactose for her milk?

A

Yes - can generate galactose from glucose pathway to make lactose