Biochemistry - Metabolism in Health And Disease part 1 Flashcards

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1
Q

What are some of the long term effects of diabetes? Why do they occur?

A

Blindness - due to glycoslylation of retinal proteins

Amputation - especially of extremities, due to glycosylation of blood vessels and heamoglobin

Renal failure - due to kidneys trying to get rid of excess glucose

Heart attack and stroke - due to high lipid level in blood

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2
Q

What are some of the ways diabetes can be diagnosed?

A

Test fasting blood glucose levels - initial step, diabetes usually confirmed by more tests

Glucose tolerance test (GTT) - if patient has diabetes they have:

  • higher starting blood glucose
  • higher peak
  • slower decrease in blood glucose

Urine glucose - dip stick test

Glycosylated haemoglobin - best long term measurement, longer term indication

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3
Q

What is the definition of type 1 diabetes?

A

A heterogenous group of syndromes characterised by an elevation of fasting blood glucose caused by an absolute deficiency in insulin.

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4
Q

What is thought to be the cause of type 1 diabetes?

A

Genetic (HLA genes) and environmental (Coxsackie virus)

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5
Q

What is a normal fasting blood glucose level?

What is a high (diabetic) fasting blood glucose level?

What is a pre diabetic blood glucose level?

A

4 - 6mM

> 8mM

6 - 8mM

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6
Q

How does ketoacidosis occur in type 1 diabetes?

A
  1. Lipolysis triggered - fatty acids (FAs) released into blood and taken up by the liver
  2. FAs broken down in beta-oxidation pathway
  3. Acetyl CoA produced which feeds into the Krebs cycle forming NADH and FADH2 which are used to make ATP
  4. Too much acetyl CoA produced Krebs cycle is overloaded. Excess acetyl CoA is used to produce ketone bodies (ketogenesis) and acetoacetate
  5. The acetoacetate decomposes to acetone which causes ‘pear drop smelling’ breath
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7
Q

What is the definition of type 2 diabetes?

A

A heterogenous group of symptoms characterised by an elevation of fasting blood glucose caused by a relative deficiency in insulin

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8
Q

What is insulin resistance?

A

A condition in which the peripheral tissues (such as muscle and adipose), lose the ability to uptake plasma glucose efficiently at physiological concentrations of insulin.

The pancreas secretes more insulin to compensate.

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9
Q

In humans what enantiomer are most metabolically relevant substances?

In humans what enantiomers are amino acids?

A

D-isomers

L-isomers

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10
Q

What is the name of the ring structure adopted by glucose?

Why is it called this?

A

Pyranose

Because it has 5 carbons in its ring

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11
Q

What is the name of the ring structure adopted by fructose?

Why is it called this?

A

A furanose structure

Because it has 4 carbons in a ring structure

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12
Q

What monosaccharides make up these common disaccharides?

  • sucrose
  • lactose
  • maltose
A

Glucose - fructose

Galactose - glucose

Glucose - glucose

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13
Q

What are the four types of polysaccharide?

A

Homopolysaccharides - made of one sugar type

Heteropolysaccharides - made of different sugar types

Unbalanced/ linear polysaccharides

Branched polysaccharides

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14
Q

What are the two bond types in glycogen, what enzymes break them and what conditions activate these enzymes?

A

Alpha 1-4 glycosidic bond - broken by glycogen phosphorylase, activated by starvation conditions (by glucagon and cortisol)

Alpha 1-6 linkage - broken by a de-branching enzyme which is activated under the same conditions as glycogen phosphorylase

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15
Q

Where is glycogen stored?

A

Skeletal muscle and liver tissues

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16
Q

What bonds link cellulose?

A

Beta 1-4 bonds

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17
Q

What are glycolipids? How are they used?

A

Lipids with a covalently bound oligosaccharide example of use: markers for cellular recognition on outer surface of eukaryotic cell membrane

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18
Q

What are glycoproteins? Where are glycoproteins used?

A

Proteins with a small oligosaccharide attached

Secreted extracellular proteins and integral membrane proteins are often glycoproteins

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19
Q

What amino acid do O-linked proteins form a linkage with?

What amino acids do N-linked proteins form a linkage with?

A

Serine

Asparagine

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20
Q

Where is aggrecan found? What type of glycomolecule is it?

A

In cartilage. It is a proteoglycan.

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21
Q

What are the three types of transporter? Describe them.

A

Uniport - one molecule transported at a time, driven by concentration gradient

Symport - two molecules transported at a time

Antiport - one molecule in one out

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22
Q

What is the apo form of a uni port transporter?

What is the holo form?

A

When the ligand isn’t bound

When the ligand is bound

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23
Q

Which molecule does GLUT have a high affinity for?

What areas of the body are each GLUT protein associated with?

A

Glucose

GLUT1 - erythrocytes and brain
GLUT2 - liver, kidney, intestine and pancreatic beta cells
GLUT3 - neurons
GLUT4 - adipose tissue and skeletal muscle
GLUT5 - small intestine, testes and muscles
GLUT7 - gluconeogenic tissues

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24
Q

Which is the only bidirectional GLUT transporter?

A

GLUT2

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25
Q

Which is the only GLUT to respond to insulin?

A

GLUT4

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26
Q

Which is the only GLUT to not be expressed in the phospholipid membrane?

Where is it expressed instead?

A

GLUT7

The endoplasmic reticulum

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27
Q

What are the metabolic fates of pyruvate?

A

Can be converted to acetyl coA and oxyaloacetate which feed into the kerbs cycle

Add an amino group to form alanine

In yeast pyruvate is converted to ethanol

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28
Q

What are the three metabolic control points in glycolysis?

A

The phosphorylation of glucose

The formation of fructose 1, 6 bisphosphate

The formation of pyruvate

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29
Q

What is the purpose of converting glucose to glucose-6-phosphate at the start of glycolysis? Why is this an important step?

A

To trap glucose in the cell. This is important in the liver where the GLUT2 transporter is bidirectional

30
Q

What coenzyme do enzymes that require ATP require? Why do they need it?

A

Magnesium. ATP has four negative charges and Mg2+ neutralises two of these

31
Q

What is the activity of hexokinase 1 like under starvation conditions?

A

Has 100% activity even at starvation conditions. It has a relatively low Vmax

32
Q

What is the activity of hexokinase/ glucokinase 4 like under starvation conditions?

A

Has low activity under starvation conditions, responds to high glucose levels

33
Q

What effect does fructose-6-phosphate have on glucokinase? Why?

A

It inhibits it as you do not need to produce more G6P

34
Q

What are the positive regulators for the conversion of fructose-6-phosphate to fructose 1,6-bisphosphate?

What are the negative regulators?

A

AMP, ADP and fructose 2, 6-bisphosphate

ATP and citrate

35
Q

What is the most common cause of haemolytic anaemia?

A

Glucose-6-phosphate dehydrogenase deficiency

36
Q

What are some of the functions of lipids?

A

Energy storage - lipid storage is virtually unlimited compared to only 500g of glycogen

Formation of membranes

Co factors - e.g. vitamin K

Signalling

Antioxidants - e.g. vitamin E

37
Q

How many carbons can a lipid fatty acid hydrocarbon tail have?

A

2 - 124

38
Q

How many double bonds does a saturated fatty acid have?

How many double bonds does an monounsaturated fatty acid have?

How many double bonds does a polyunsaturated fatty acid have?

A

None

1

1+

39
Q

What form do adipocytes store fatty acids in?

A

Triacylglycerols

40
Q

What enzymes hydrolyse the ester bond in triacylglycerols?

A

Lipases

41
Q

Describe these phospholipid head groups:

  • phospatidylcholine
  • phosphatidylinositol 4,5-bisphosphate
  • cardiolipin
A

Most common, found in high levels in the phospholipid membrane, used as an emulsifier in the food industry

Important for signalling pathways

Found in high concentrations in mitochondria, biomarker for apoptosis

42
Q

Describe the head groups of these sphingolipids:

  • ceramide
  • sphingomyelin
  • glycolipids
A

Simplest, head group is a single hydrogen

Head group is phosphocholine, found in myelin sheath

Sugar attached, part of the process of defining blood grouping

43
Q

What are these sterioid hormones important for:

  • cortisol
  • aldersterone
  • prednisone and prednisolone
  • brassionolide
A

Glucose metabolism

Salt excretion

Anti-inflammatory drugs

Found in plants

44
Q

What are the two main functions of bile acids?

A

A detergent in the small intestine - solubilise dietary fats

Mechanism for getting rid of cholesterol

45
Q

What are the two functions of vitamin K?

A

Required by blood clotting proteins e.g. prothrombin

Required by calcium binding proteins, so is important in bone formation

46
Q

What are the three groups of arachidonic acids?

A

Prostaglandins - inflammation and pain

Thromboxanes - blood clotting

Leukotriene - smooth muscle function of lungs

47
Q

What forms prostaglandins and thromboxanes?

What inhibits these enzymes?

A

Cyclo-oxegnases (cox enzymes)

Steroidal anti-inflammatory drugs (NSAIE) e.g. aspirin, paracetamol and ibuprofen

48
Q

What are polyketides?

A

Compounds that have been or are used clinically, starting point is a plant, fungus or bacteria e.g. erythromycin and antibiotic

49
Q

What is the lipoprotein pathway?

A

A way of transporting fats around the body as cholestrol and triglycerols (both of which are hydrophobic)

50
Q

What is the center of a lipoprotein like?

A

Highly hydrophobic

51
Q

What are the four classes of glycoproteins?

A

Chylomicrons
VLDL - very low density lipoprotein
LDL - low density lipoprotein
HDL - high density lipoprotein

52
Q

In which sterioisomeric form are hexose monosaccharides found in living organisms?

A

D sterioisomers

53
Q

What is the major form of energy storage in the body?

A

Triacylglycerols

54
Q

What type of glycomolecule determines blood group in partL

A

Glycosphingolipids

55
Q

What effect does high F26BP levels have on glycolysis?

What effect do low levels have?

A

Stimulates glycolysis, inhibits gluconeogenesis

Opposite

56
Q

What does PFK1 do in glycolysis?

What does F26BP do?

A

Converts fructose-6-phosphate to fructose 1, 6-bisphosphate

Activates PFK1

57
Q

What happens when PFK2/ F 2,6-bisphosphatase is phosphorylated in the liver by protein kinase A?

A

PFK2 is inhibited and F26BPase is activated, this lowers the concentration of fructose 2,6-bisphosphate so inhibits glycolysis

58
Q

What are the five main roles of NADPH?

A

Reductive biosynthesis - e.g. synthesis of fatty acids

Reduction of hydrogen peroxide

Cytochrome p450 - drug metabolism

Phagocytosis

Synthesis of nitric oxide - a basodilator which relaxes smooth muscle in blood vessels

59
Q

What are the tree enzymes involved in the reduction of hydrogen peroxide?

A

Superoxide dismutase, catalase and glutathione peroxidase

60
Q

What are the three amino acids that make up glutathione?

Which amino acid in glutathione forms a disulfide bridge with another glutathione molecule? Why?

What is the oxidised form of glutathione?

A

Glycine, cysteine and glutamate

Cysteine because it has a SH which is reduced to G-SH

G-S-S-G

61
Q

Where are polyunsaturated fatty acids found?

A

In fish oils and fruits e.g. Avocado

62
Q

What type of bonds are found in triglycerols?

What types of bond are found in a sphingolipid?

A

Ester bonds

Amide bonds

63
Q

What do adipocytes secrete?

A

Cytokines

64
Q

What are chylomicrons and VLDL?

What are LDL and HDL?

A

Triacylglyerol rich lipoproteins body uses to transport fats from tissue a to b

Cholesterol rich lipoproteins which transport cholesterol to the cells or peripheral (non-liver) tissue for recycling

65
Q

Which apo protein is an identifier for chylomicrons?

Which is an identifier for VLDL and LDL?

A

ApoB-48

ApoB-100

66
Q

Where is hexokinase 4 found predominantly?

A

In the liver and pancreas

67
Q

How is hexokinase 1 controlled?

What regulate hexokinase 4?

A

Through product inhibition , glucose-6-phosphate (product) inhibits the enzyme so the cell won’t take up more glucose

Insulin at transcriptional levels, glucose (positive regulation) and fructose-6-phosphate (positive regulation)

68
Q

What is the oxidised form of gluthaione?

What is the reduced form?

A

GSSG

GSH

69
Q

Why is pyruvate converted to lactate?

A

To regenerate NAD+ allowing further glycolysis

70
Q

Two organelles where cytochrome p-450 is found?

A

Mitochondria and endoplasmic retuculium (microsomal system)