MEH 1.2 Flashcards
What is the general formula of carbohydrates?
(CH20)n
Which glycosidic bonds are present in glycogen?
Alpha 1,4 and 1,6
What enzyme is present in the saliva and begins carbohydrate breakdown?
amylase
What enzymes are involved in carbohydrate breakdown in the small intestine?
Disaccharidases: Lactase Sucrase Pancreatic amylase Isomaltase
What is primary lactase deficiency?
Absence of lactase
Only occurs in adults
What symptoms are associated with lactose intolerance?
Diarrhoea Bloating Vomiting Flatulence Rumbling stomach
What is secondary lactase deficiency and how does it differ from primary lactase deficiency?
Caused by injury to small intestine - gastroenteritis, coeliac disease, crohn’s disease, ulcerative colitis
- occurs in both infants and adults
- generally reversible
How are monosaccharides taken up into the intestinal epithelial cells?
Active transport by sodium-dependent glucose transporter (SGLT1)
How are monosaccharides transported into the blood from the epithelial cells?
Facilitated transported using GLUT2 transporter
Where is GLUT2 expressed?
Kidney, liver, pancreatic beta cells, small intestine
Where is GLUT4 expressed, why is this transported particularly important?
Adipose tissue
Striated muscle
Insulin regulated
Which cells have an absolute requirement for glucose?
Erythrocytes - no mitochondria Neutrophils Innermost cells of kidney medulla Lens of the eye CNS prefers glucose
Give an example for the clinical application of glycolysis.
The rate is increased in cancer.
This can be measured by using a radioactive modified hexokinase substrate (FDG) and imagine with position emission tomography.
Which enzyme is the main, key regulator of glycolysis?
Phosphofructokinase
How is PFK allosterically regulated?
ATP inhibits
AMP stimulates
How is PFK hormonally regulated?
Insulin stimulates
Glucagon inhibits
What is the difference between hyperlactaemia and lactic acidosis?
Hyperlactaemia - 2-5mM, no change in blood pH (buffered)
Lactic acidosis - >5mM, blood pH lowered
Deficiency of which 3 enzymes will result in galactosaemia?
- Galactokinase
- Uridyl transferase
- UDP- galactose epimerise
Which enzyme is absent in essential fructosuria, is there any clinical significance?
Fructokinase
No clinical signs, fructose in urine
Which enzyme is absent in fructose intolerance, what is the clinical significance?
Aldolase
Fructose-1-P accumulates in the liver, causing damage
Treatment - remove fructose from diet
What is the starting substrate of the pentose-phosphate pathway?
Glucose-6-phosphate
Which enzyme is responsible for the first step in the pentose phosphate pathway?
G6PDH
Pentose phosphate pathway is an important source of NADH. What is this required for?
- reducing power for biosynthesis of steroids and fatty acids
- maintenance of GSH levels
- detoxification reactions
Other than NADPH, what else does the pentose phosphate pathway produce?
C5- sugar ribose
What is ribose needed for?
Synthesis of nucleotides, DNA and RNA
What is the rate-limiting enzyme of the pentose-phosphate pathway?
Glucose 6-phosphate deyhydrogenase
Where do both glycolysis and the pentose phosphate pathway occur?
Cytosol
What dietary component does the enzyme salivary amylase hydrolyse?
Starch.
Amylase in both saliva and pancreas break down starch and glycogen to dextrins and monosaccharides.
What is congenital lactase deficiency?
Autosomal recessive defect in lactase gene - extremely rare
Cannot digest breast milk
Which enzyme converts DHAP to glycerol phosphate?
Glycerol 3-phosohate deyhydrogenase
Which tissues produce glycerol phosphate?
Adipose & Liver
What is glycerol phosphate used for?
Combined with fatty acids to form TAG in liver and adipose tissue.
Which enzyme coverts 1,3 bpg to 2,3 bpg?
Bisphosphoglycerate mutase
Which cells produce 2,3-BPG, what does it do?
Red blood cells, promotes release of oxygen
Which enzyme is used to regenerate NAD+ from NADH in anaerobic conditions or cells lacking electron chain?
Lactate dehydrogenase:
NADH+ + pyruvate -> lactate + NAD+
What is the normal plasma lactate concentration?
<1 mM
What lactate conc is considered hyperlactaemia?
2-5 mM
What are the consequences of hyperlactaemia?
Still below renal threshold, no change in blood pH as buffered
What lactate conc is considered lactic acidosis?
> 5mM
Why is lactic acidosis an important clinical marker?
Suggests acutely unwell patient. Lactate levels above renal threshold and pH of blood becomes lowered.
Deficiency of which 3 enzymes can cause galactosaemia?
UDP- galactose epimerase
Uridyl transferase
Galactokinase
What occurs in essential fructosuria?
Fructokinase deficiency.
No conversion of fructose to fructose-1-P, fructose excreted in urine.
No clinical signs
What occurs in fructose intolerance?
Aldolase enzyme deficiency.
Accumulation of Fructose 1-P in the liver, causing liver damage.
What substate goes the pentose-phosphate pathway start from?
Glucose 6P
What enzyme is the rate limiting enzyme in the pentose-phosphate pathway?
Glucose-6P- dehydrogenase
What does the pentose-phosphate pathway produce?
NADPH Ribose sugar (5C)
What is NADPH needed for?
Reducing power for biosynthesis
Maintenance of GSH levels
Steroid biosynthesis
Detoxification reactions
What is ribose sugar needed for?
Synthesis of RNA, DNA, co-enzymes and nucleotides
Does the pentose-phosphate pathway produce ATP?
No
Explain the clinical consequences of severe protein deficiency in children.
Reduced rate of protein synthesis as lack of amino acids:
Growth failure.
Tiredness, weakness, poor exercise tolerance
Impaired mental development
Negative nitrogen balance due to Nin < Nout
Oedema
Increased risk of infection- reduced immunoglobulin
Anaemia- reduced haemoglobin synthesis.
Fatty liver- reduced lipoprotein synthesis.
What reaction is catalysed by creatine kinase?
Creatine phosphate + ADP -> ATP + creatine
What conditions may lead to increased plasma lactate?
Decreased utilisation: liver disease, thiamine deficiency and during alcohol metabolism.
Increased production: strenuous exercise, hearty eating, shock and congestive heart disease
Compare and contrast the functions of glycolysis in adipose tissue, skeletal muscle and red blood cells.
Red blood cells -only way to produce ATP, 2,3 -BPG intermediate
Skeletal muscle - ATP during anaerobic conditions
Adipose - minor ATP source, glycerol phosphate production
Which is the most common form and more severe form of galactosaemia?
Galactose -1P uridyl transferase deficicency
Which form of galactosaemia is less severe and less common?
Galactokinase deficiency
Why is Uridyl transferase deficiency more severe than a galactokinase deficiency?
Both galactose and Galactose 1P accumulate in tissues
What cofactor is needed for glutathione peroxidase?
Selenium
