systems to cells

Question 1

describe the make up of ATP

Answer 1

Adenine- two ring structure attached to ribose sugar.
adenine and ribose sugar are attached to adenosine. which is attached to tri (3) phosphate groups.

Question 2

difference between hypoglycaemia and hyperglycaemia?

Answer 2

hypo- low blood glucose
hyper- high blood glucose

Question 3

what is gluconeogenesis?

Answer 3

metabolic pathway that results in the generation of glucose from lactate or amino acid-
reverses glycolysis.
insulin turns this off and glucagon turns this on.

Question 4

explain the reaction involved in the breakdown and synthesis of glycogen

Answer 4

when blood sugars rise. insulin is secreted from pancreatic beta cells.
glucose is converted to glucose-6-phosphate by hexokinase. this is reversed by glucose-6- phosphatase.

Then it’s converted to glucose-1- phosphate by phosphoglucomutase. this is a reversible reaction by the same enzyme.

Then it is stored as glycogen by glycogen synthase. by protein phosphatase 1. when blood sugar drops glycogen is converted back to glucose-1-phosphate by glycogen phosphorylase. THIS REACTION IS IRREVERSIBLE!.
goes back through pathway until it is Brocken down into glucose.
regulated by turning on/ off the enzymes.

Question 4

explain different ways enzymes are regulated (turned on/off)

Answer 4

phosphorylation- involves addition of phosphate from ATP by kinases.
dephosphorylation- removal of phosphate by phophatases.

Question 5

how glucagon degrades glycogen?

Answer 5

cAMP is a secondary messenger synthesised from ATP which activates protein kinase A (PKA).
PKA phosphorylates glycogen synthase (turning it off)
PKA phosphorylates glycogen phosphorylase (turning it on).
glycolysis is tuned off

Question 6

how insulin promotes glycogen synthesis

Answer 6

insulin switches on protein phosphatase 1 by AKT. which dephosphorylates glycogen phosphorylase, leading to turned on glycogen synthase. = glycogen
glycolysis is turned on

Question 7

what is the rate determining step?

Answer 7

the slowest step in a reaction, as the energy requirement is larger.
also seen as the irreversible steps eg glycogen synthase and glycogen phosphorylase.

Question 8

what part of the pancreas secretes hormones?

Answer 8

islets of langerhans

Question 9

translation of preproinsulin

Answer 9

proporinsulin has signal peptide at the N terminus guiding into the ER.
the signal peptide is cleaved off in ER which results in proinsulin. folding only happens in the ER.
proinsulin held stable due to disulphide bonds
proinsulin moved to Golgi and packaged into secretory vehicles.
only have biologically active insulin in nature secretory vehicles after c peptide is released.

Question 10

what is regulated exocytosis?

Answer 10

release of controlled hormones from vesicles at a specific signal eg
release of insulin in response to glucose levels. and GLUT-4 taking up excess glucose by activation of AKT

Question 11

how glucose gets from outside beta cell to inside beta cell?

Answer 11

GLUT-2 transporter. (low affinity/high KM)

Question 12

the two glucose sensors in beta cells?

Answer 12

GLUT 2
glucokinase

Question 13

what triggers insulin release in beta cells?

Answer 13

glucose phosphorylation in beta cells uses low affinity/ high KM enzyme glucokinase (same as hexokinase but only in beta cells)
-therefore converts glucose to glucose 6 phosphate results in glycolysis and the rise of ATP.
- as ATP increases, it closes ATP sensitive potassium channels. results in the depolarisation of cell membrane.
depolarisation opens calcium channels allowing calcium influx
-triggering insulin exocytosis= release of insulin to glucose levels

Question 14

meaning of a high KM?

Answer 14

enzyme is more active at a higher glucose concentration

Question 15

structure and function of insulin receptor?

Answer 15

structure- held together by. disulphide bonds. contains 2 alpha subunits at insulin binding site outside cell membrane.
contains 2 beta subunits inside membrane.

Question 16

how does insulin exert its effect on target tissue?

Answer 16

1) alpha subunits go through conformational change which activates intrinsic tyrosine kinase activity in betas subunits.
2) the activated beta subunits phosphorylate tyrosine residues on themselves called (AUTOPHOSPHORYLATION) enhancing kinase activity.
2) kinase can phosphorylate several intracellular signalling proteins such as (IRS-1).
3) IRS-1 are phosphorylated on tyrosine residues. these phosphorylated sites serve as docking points for proteins such as (SH2 domains). - bind tyrosine residues in specificity pocket.
4) THIS ACTIVATES THE ENZYME ‘AKT’

Question 17

how insulin stimulates glucose uptake in fat and muscle cells?

Answer 17

GLUT-4 transporter (muscle, heart and fat)
insulin present-
activated AKT by binding of insulin receptors traffics GLUT-4 to cell surface - to take us excess glucose.= regulated exocytosis.
no insulin- GLUT-4 is stored in specialised vehicles in cytoplasm of adipose and muscle cells.

Question 18

2 functions of AKT enzyme in fat cells and liver?

Answer 18

fat cells-
activates GLUT-4 trafficking to the cell surface to take up excess glucose

liver-
phosphorylates and activates protein phosphatase 1 (which promotes glycogen storage by activated glycogen synthase and turns off glycogen phosphorylase.

Question 19

how gene expression and sub cellular changes are activated by insulin signalling?

Answer 19

when insulin binds to its receptor it activates protein IRS-1, which influences activity of transcription factors and gene expression.

1) activates LXR transcription factor (liver&fat)
2) LXR in fat drives expression of SREBP1 transcription factor
3) which turns fat storage on

Question 20

how gene mapping strategies can be used to identify affected chromosomal domains?

Answer 20

gene mapping using STRs,
STRs are microsatelites

Question 21

what are MOXA mutations ?

Answer 21

specific genetic alterations caused from point mutations, deletions, insertions in gene associated in metabolic pathways, signalling cascades or structural proteins

Question 22

example of single gene conditions?

Answer 22

cystic fibrosis and sickle cell,
hemochromatosis, and Tay-Sachs

Question 23

what is a haplotype?

Answer 23

set of DNA variants along a single chromosome that tends to be inherited together.

Question 24

GWAS analyses are likely to shed light on genetic factors contributing to which of the following conditions?

Answer 24

prostate cancer

Question 25

PKC and oxidative stress causing diabetes?

Answer 25

PKC= as blood glucose increases, DAG synthesis increases. which leads to an activation of PKC pathway (damages kidney and nerves)

Oxidative stress= leads to an increased production of reactive oxygen species (ROS) which leads to endothelial dysfunction. this can result in insulin resistance and damage pancreatic beta cells.

Question 26

blood sugar levels response to no exercise and some.

Answer 26

low levels of physical activity can lead to a hyperglycaemic state which can result in glucose toxicity and endothelial dysfunction due to enhanced PKC activity and oxidative stress.
physical activity manages blood sugar by increasing ATP consumption and carb usage. resulting in euglucemia (normal blood sugar range)

Question 27

blood sugar levels response to resistance training and muscle mass

Answer 27

muscle contraction increases the movement of GLUT 4 transporters to the cell membrane surface (for up to 24 hours) - which means insulin mediated effects last longer eg insulin sensitivity.
more muscle mass= more glucose delivery and storage by enhanced insulin affect

Question 28

negative effects on high intensity exercise on blood glucose levels?

Answer 28

temporary post exercise hyperglycaemia - addition of glucongenesis. body dumps a load of glucose for energy.

Question 29

what is starch made up of?

Answer 29

amylose and amylopectin (more easily digested)

Question 30

how a keto diet influences diabetes and the risks of this?

Answer 30

T2D= improves insulin sensitivity
T1D= hypoglycaemia

risk- changes dominant substrate to fat, thereby the liver converts fatty acids in ketones. which leads to ketoacidosis (severe lack of insulin in the body)

Question 31

at rest, what is the preferred substrate for ATP generation?

Answer 31

free fatty acids