Biochemistry - Metabolism in Health And Disease part 1 Flashcards
What are some of the long term effects of diabetes? Why do they occur?
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
What are some of the ways diabetes can be diagnosed?
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
What is the definition of type 1 diabetes?
A heterogenous group of syndromes characterised by an elevation of fasting blood glucose caused by an absolute deficiency in insulin.
What is thought to be the cause of type 1 diabetes?
Genetic (HLA genes) and environmental (Coxsackie virus)
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?
4 - 6mM
> 8mM
6 - 8mM
How does ketoacidosis occur in type 1 diabetes?
- Lipolysis triggered - fatty acids (FAs) released into blood and taken up by the liver
- FAs broken down in beta-oxidation pathway
- Acetyl CoA produced which feeds into the Krebs cycle forming NADH and FADH2 which are used to make ATP
- Too much acetyl CoA produced Krebs cycle is overloaded. Excess acetyl CoA is used to produce ketone bodies (ketogenesis) and acetoacetate
- The acetoacetate decomposes to acetone which causes ‘pear drop smelling’ breath
What is the definition of type 2 diabetes?
A heterogenous group of symptoms characterised by an elevation of fasting blood glucose caused by a relative deficiency in insulin
What is insulin resistance?
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.
In humans what enantiomer are most metabolically relevant substances?
In humans what enantiomers are amino acids?
D-isomers
L-isomers
What is the name of the ring structure adopted by glucose?
Why is it called this?
Pyranose
Because it has 5 carbons in its ring
What is the name of the ring structure adopted by fructose?
Why is it called this?
A furanose structure
Because it has 4 carbons in a ring structure
What monosaccharides make up these common disaccharides?
- sucrose
- lactose
- maltose
Glucose - fructose
Galactose - glucose
Glucose - glucose
What are the four types of polysaccharide?
Homopolysaccharides - made of one sugar type
Heteropolysaccharides - made of different sugar types
Unbalanced/ linear polysaccharides
Branched polysaccharides
What are the two bond types in glycogen, what enzymes break them and what conditions activate these enzymes?
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
Where is glycogen stored?
Skeletal muscle and liver tissues
What bonds link cellulose?
Beta 1-4 bonds
What are glycolipids? How are they used?
Lipids with a covalently bound oligosaccharide example of use: markers for cellular recognition on outer surface of eukaryotic cell membrane
What are glycoproteins? Where are glycoproteins used?
Proteins with a small oligosaccharide attached
Secreted extracellular proteins and integral membrane proteins are often glycoproteins
What amino acid do O-linked proteins form a linkage with?
What amino acids do N-linked proteins form a linkage with?
Serine
Asparagine
Where is aggrecan found? What type of glycomolecule is it?
In cartilage. It is a proteoglycan.
What are the three types of transporter? Describe them.
Uniport - one molecule transported at a time, driven by concentration gradient
Symport - two molecules transported at a time
Antiport - one molecule in one out
What is the apo form of a uni port transporter?
What is the holo form?
When the ligand isn’t bound
When the ligand is bound
Which molecule does GLUT have a high affinity for?
What areas of the body are each GLUT protein associated with?
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
Which is the only bidirectional GLUT transporter?
GLUT2
Which is the only GLUT to respond to insulin?
GLUT4
Which is the only GLUT to not be expressed in the phospholipid membrane?
Where is it expressed instead?
GLUT7
The endoplasmic reticulum
What are the metabolic fates of pyruvate?
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
What are the three metabolic control points in glycolysis?
The phosphorylation of glucose
The formation of fructose 1, 6 bisphosphate
The formation of pyruvate
What is the purpose of converting glucose to glucose-6-phosphate at the start of glycolysis? Why is this an important step?
To trap glucose in the cell. This is important in the liver where the GLUT2 transporter is bidirectional
What coenzyme do enzymes that require ATP require? Why do they need it?
Magnesium. ATP has four negative charges and Mg2+ neutralises two of these
What is the activity of hexokinase 1 like under starvation conditions?
Has 100% activity even at starvation conditions. It has a relatively low Vmax
What is the activity of hexokinase/ glucokinase 4 like under starvation conditions?
Has low activity under starvation conditions, responds to high glucose levels
What effect does fructose-6-phosphate have on glucokinase? Why?
It inhibits it as you do not need to produce more G6P
What are the positive regulators for the conversion of fructose-6-phosphate to fructose 1,6-bisphosphate?
What are the negative regulators?
AMP, ADP and fructose 2, 6-bisphosphate
ATP and citrate
What is the most common cause of haemolytic anaemia?
Glucose-6-phosphate dehydrogenase deficiency
What are some of the functions of lipids?
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
How many carbons can a lipid fatty acid hydrocarbon tail have?
2 - 124
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?
None
1
1+
What form do adipocytes store fatty acids in?
Triacylglycerols
What enzymes hydrolyse the ester bond in triacylglycerols?
Lipases
Describe these phospholipid head groups:
- phospatidylcholine
- phosphatidylinositol 4,5-bisphosphate
- cardiolipin
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
Describe the head groups of these sphingolipids:
- ceramide
- sphingomyelin
- glycolipids
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
What are these sterioid hormones important for:
- cortisol
- aldersterone
- prednisone and prednisolone
- brassionolide
Glucose metabolism
Salt excretion
Anti-inflammatory drugs
Found in plants
What are the two main functions of bile acids?
A detergent in the small intestine - solubilise dietary fats
Mechanism for getting rid of cholesterol
What are the two functions of vitamin K?
Required by blood clotting proteins e.g. prothrombin
Required by calcium binding proteins, so is important in bone formation
What are the three groups of arachidonic acids?
Prostaglandins - inflammation and pain
Thromboxanes - blood clotting
Leukotriene - smooth muscle function of lungs
What forms prostaglandins and thromboxanes?
What inhibits these enzymes?
Cyclo-oxegnases (cox enzymes)
Steroidal anti-inflammatory drugs (NSAIE) e.g. aspirin, paracetamol and ibuprofen
What are polyketides?
Compounds that have been or are used clinically, starting point is a plant, fungus or bacteria e.g. erythromycin and antibiotic
What is the lipoprotein pathway?
A way of transporting fats around the body as cholestrol and triglycerols (both of which are hydrophobic)
What is the center of a lipoprotein like?
Highly hydrophobic
What are the four classes of glycoproteins?
Chylomicrons
VLDL - very low density lipoprotein
LDL - low density lipoprotein
HDL - high density lipoprotein
In which sterioisomeric form are hexose monosaccharides found in living organisms?
D sterioisomers
What is the major form of energy storage in the body?
Triacylglycerols
What type of glycomolecule determines blood group in partL
Glycosphingolipids
What effect does high F26BP levels have on glycolysis?
What effect do low levels have?
Stimulates glycolysis, inhibits gluconeogenesis
Opposite
What does PFK1 do in glycolysis?
What does F26BP do?
Converts fructose-6-phosphate to fructose 1, 6-bisphosphate
Activates PFK1
What happens when PFK2/ F 2,6-bisphosphatase is phosphorylated in the liver by protein kinase A?
PFK2 is inhibited and F26BPase is activated, this lowers the concentration of fructose 2,6-bisphosphate so inhibits glycolysis
What are the five main roles of NADPH?
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
What are the tree enzymes involved in the reduction of hydrogen peroxide?
Superoxide dismutase, catalase and glutathione peroxidase
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?
Glycine, cysteine and glutamate
Cysteine because it has a SH which is reduced to G-SH
G-S-S-G
Where are polyunsaturated fatty acids found?
In fish oils and fruits e.g. Avocado
What type of bonds are found in triglycerols?
What types of bond are found in a sphingolipid?
Ester bonds
Amide bonds
What do adipocytes secrete?
Cytokines
What are chylomicrons and VLDL?
What are LDL and HDL?
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
Which apo protein is an identifier for chylomicrons?
Which is an identifier for VLDL and LDL?
ApoB-48
ApoB-100
Where is hexokinase 4 found predominantly?
In the liver and pancreas
How is hexokinase 1 controlled?
What regulate hexokinase 4?
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)
What is the oxidised form of gluthaione?
What is the reduced form?
GSSG
GSH
Why is pyruvate converted to lactate?
To regenerate NAD+ allowing further glycolysis
Two organelles where cytochrome p-450 is found?
Mitochondria and endoplasmic retuculium (microsomal system)
