S5 Carbohydrate Metabolism Flashcards
What are the 4 main stages of carbohydrate metabolism?
1) break down of fuel molecules (proteins, carbs, lipids) to monomers (monosaccharides i.e. glucose)
2) Break down to metabolic intermediates: glycolysis + link reaction
3. ) Tricarboxylic acid (Krebs) cycle
4. ) Oxidative phosphorylation
Where in the body does stage 1 of carb metabolism occur?
- extracellular in the GI tract
- building block molecules are absorbed from GI tract into circulation
What enzymes are involved in stage 1 and what do they do/where?
- Salivary Amylases- break down starch, glycogen in saliva to dextrin
- Pancreatic amylases- break down carbs to monosaccharides
- In the small intestine:
—> Lactase (breaks down lactose into glucose and galactose)
—> sucrase (breaks down sucrose into fructose and glucose)
—> pancreatic amylase (breaks alpha 1-4 bonds)
—> isomaltase (breaks alpha 1-6 bonds)
Why can’t cellulose be digested by humans?
Humans do not have enzymes to break down the B,1-4 linkages in dietary fibres
BETA Bonds are diff to alpha bonds
(I.e. no cellulase)
A) What molecules make up lactose? B) what is lactose intolerance + how is it caused? C) what foods contain lactose? D) symptoms? E) types of lactose intolerance?
A) Glucose and galactose
B) inability to break down lactose- small intestine stops making enough of lactase to digest and break down the lactose
C) Milk, cream, yoghurt, cheese
D) bloating/cramps, flatten each, diarrhoea, vomiting, rumbling stomach
E) - primary lactase deficiency: absence of lactase persistence allele (adults only)
- secondary lactase deficiency: caused by injury to SI (gastroenteritis, coeliac, crohns)
- congenital lactase deficiency: autosomal recessive defect in lactase gene, cannot digest breast milk
How are monosaccharides, such as glucose, absorbed into circulation?
- using ion transporters
1. Active transport into intestinal epithelial cells by sodium dependent glucose transporter 1 (SGLT1)
2. Passive transport of glucose via GLUT 2 into blood - the NA pump generates a gradient
A) What is the rough conc of glucose in the blood?
B) what tissues require glucose?
C) what does the brain use in times of starvation?
A) 5mM
B) RBC, neutrophils, innermost of kidney medulla and lens of the eye
C) ketone bodies
A) Where does glycolysis occur
B) characteristics of glycolysis
C) Functions/what does it produce?
A) occurs in all tissues and in the cytosol
B) - it is an exergonic and oxidative process
C) - oxidation of glucose
- NADH production (2 per glucose)
- 2 net ATP produced per glucose
- produces c6 and c3 intermediates
A) How many steps is glycolysis?
B) why so many steps?
A) 10 B) - conserves energy - fine control - interconnections with other pathways - intermediates produced - some parts reversible
What are the most important enzymes to remember in glycolysis and what do they do and what step is each involved in?
- In step 1: hexokinase- phosphorylation of glucose to Glucose-6-P
- In step 3: phosphofructokinase-1: Fructose-6-P to Fructose 1,6-bis-P: first committing step
- in step 10: Pyruvate kinase: catalyses transfer of po4 from PEP to ADP- producing ATP and pyruvate
A) Why is glucose phosphorylated in glycolysis?
B) what step does this occur in
C) what enzyme catalyses this
A) makes glucose more negatively charged so that it cannot pass back across membrane and makes it more reactive
B) step 1
C) hexokinase
What are the products of glycolysis and where does each go?
- 2 pyruvate: to link reaction
- 2 NADH: to ETC
- 2 net gain ATP (4 produced but 2 lost at start)
What are the two important intermediates produced in glycolysis?
1) Glycerol phosphate
- produced from DHAP in step 4
- important to triglyceride and phospholipid biosynthesis
- produced from DHAP in adipose tissue and liver
2) 2,3-Bisphosphoglycerate (2,3-BPG)
- produced from 1,3-bisphosphoglycerate in step 6
- in RBC
- important regulator of oxygen affinity in HB (promotes its release)
- without it, hb would hold oxygen so tightly that it wouldn’t be released in tissues
a) Why is NAD+ production so important in glycolysis?
B) How is NAD+ regenerated?
A) - Needed to produce NADH in step 6
- NAD+ and NADH concentration is constant, glycolysis would stop if it all was converted to NADH
B)- NAD+ is regenerated from stage 4 (OP) which requires Oxygen
- RBC don’t have stage 4 ALSO if there was no oxygen NAD+ needs to be regenerated via another route —> lactate dehydrogenase
a) Outline how anaerobic glycolysis is carried out
B) equation
C) what enzyme catalyses this
a) - lactate is produced from glucose and alanine via pyruvate
- reversible
- nad+ regenerated
B) NADH + H+ + pyruvate NAD+ + Lactate
(Catalysed by Lactate dehydrogenase)
How is plasma concentration of lactate controlled?
it is produced (i.e. via red blood cells or in low o2) released into the blood and is then metabolised by the liver, heart and muscles and then disposed of in kidneys
A) what is the normal concentration of plasma lactate?
B) What is:Hyperlactaemia
C) what is: Lactic acidosis
A) <1mM
B) plasma lactate conc: 2-5mM, no change in blood pH as below renal threshold
c) plasma lactate conc above 5mM, Blood ph is lowered as it is above renal threshold and is removed in urine
What is substrate level phosphorylation?
Production of atp without ETC, but involving transfer of a Phosphate from a highly reactive substance,
A) where is galactose metabolised?
B) what is galactosaemia
A) liver and red blood cells
B) Inability to utilise galactose due to a deficiency in any of the enzymes, it is inherited (caused by a mutation) and lead a to the toxic accumulation of an intermediate compound.
A) A new born presents with cataracts, Jaundice, hepatomegaly (enlarged liver), renal failure, vomiting and brain damage- which enzyme would you suspect is deficient in this patient and why?
A) Uridyl transferase
- leads to the accumulation of both galactose-1-phosphate and galactose
- galactose enters another pathway to form galactitol- forms cataracts
- galactose-1-phosphate affects the liver function: hence leads to hepatomegaly, jaundice etc.
- most common type of galactosaemia and most severed side affects
Why do galactosaemia patients have jaundice?
- deficiency of the transferase enzyme leads to build up of toxic galactose-1-P
- this affects liver function
- one function of the liver is to breakdown old RBC into bilirubin, which is then conjugated and excreted
- build up of unconjugated bilirubin in blood gives skin a yellow colour
Why do galactosaemia patients have cataracts?
- build up of galactose, allowing galactose to enter other pathways e.g. galactose forms galactitol
- depletes NADPH levels
- these NADPH were needed to maintain the structure of disulphide bonds in proteins
- leads to inappropriate disulphide bond formation which affects the structure and hence function of proteins
- in the eye the crystalline protein is denatured leading to cataracts
What is the treatment for galactosaemia?
- exclude galactose from diet
- no milk or dairy
- antibiotics, IV fluid
What are the 3 important enzymes involved in galactose metabolism?
- galactokinase
- Uridyl transferase
- UDP-galactose epimerase
