Glycolysis

Question 1

describe the general glucose uptake by cells.

Answer 1

adipose and muscle are insulin dependent but rest are not

Question 2

compare hexokinase and glucokinase

Answer 2

glucokinase - liver and pancreatic beta cells
hexokinase - all others
Km for glucokinase is much greater
Vmax for glucokinase is higher
hexokinase is inhibited by glucose 6 phosphate
insulin induces glucokinase
hexokinase in brain and RBCs always saturated, whereas pancreas and liver can sense changes

Question 3

describe the role of glycolysis in different tissues

Answer 3

muscle: supply energy for muscle contraction
liver: glucose converted to fat or glycogen for storage in fed state, in fasted state, reversible reactions used for gluconeogenesis
RBC: derives all its ATP
Brain: glucose is primary fuel

Question 4

Describe the regulation of glycolysis

Answer 4

availability of substrate: glucose, ADP, Pi, and NAD+
more anaerobic conditions, greater dependence on glycolysis for energy
regulatory enzymes: phosphofructokinase-1, pyruvate kinase

Question 5

What is the purpose of galactose synthesis from glucose?

Answer 5

galactose needed for synthesis of glycoproteins and glycolipids in membranes and proteoglycans in extracellular matrix. UDP-galactose used by galactotransferase. In lactating mammary gland, UDPgalactose used for lactose synthesis. Specificity for galactotransferase is modified by alpha-lactalbumin, so D-glucose can be used as acceptor molecule to form lactose.

Question 6

What are the consequences of high fructose intake?

Answer 6

enhanced fatty acid,triglyceride and VLDL synthesis by liver. Fructose is metabolized by liver more rapidly than glucose, because it bypasses the rate-limiting step. Metabolism is insulin independent. Can cause liver damage

Question 7

What conditions promote the conversion of pyruvate to alanine?

Answer 7

a defect in either of hte major pathways of pyruvate utilization (conversion of acetyl coA to oxaloacetate which leads to accumulation of lactate and alanine

Question 8

what are the functions of the pentose phosphate pathway?

Answer 8

major source of NADPH for biosynthetic reactions
Major source of ribose 5-P for nucleotide synthesis
Recycling of excess pentose phosphates back to glyceraldehyde 3-phosphate and glycolysis. (important in RBCs especially)

Question 9

Describe the tissue distribution of the pentose phosphate pathway

Answer 9

Pathway is ubiquitous and enzymes are localized in the cytosol. Pathway especially active where cytochrome P45-dependent hydroxylation reactions occur and where fatty acids, cholesterol, bile acids, and steroid hormone synthesis occurs (liver and adrenal glands). RBCs and phagocytic cells have special requirement for NADPH, and are enriched in pentose phosphate pathway enzymes

Question 10

Describe the two pathways of the pentose phosphate pathway

Answer 10

oxidative branch (irreversible): functions to generate NADPH and pentoses
Non- oxidative branch (reversible): recycles excess pentose phosphates. It interconverts C6, C5, and C3 monosaccharides. The pentose phosphate pathway and glycolysis share: fructose 6 phosphate and glyceraldehyde 3 phosphate. When the need for NADPH is greater than need for pentoses, non oxidative phase allows excess pentose phosphates to be converted to glycolytic intermediates

Question 11

Describe the effect of antimalarial drugs in people with G6P DH

Answer 11

antimalarial drugs precipitate oxidative stress by increasing the production fo toxic oxygen metabolites. In normal people, ROS are reduced in reactions requiring NADPH. In individuals deficient in glu-6-p DH, there may be an inadequate supply of NADPH, and anemia may occur if person is taking an antimalarial drug

Question 12

Which vitamins have antioxidant activity?

Answer 12

Vitamin E, beta-carotene (Vitamin A precursosr) and Vit C can reduce toxic ROS to non-toxic products

Question 13

Explain the effects of ROS in killing microbes and general effects

Answer 13

ROS trigger ionic flux across membrane of phagocytic vacuoles, creating a hypertonic environment and elevated pH, which result in release and activation of proteases that attack the phagocytized microbe

Effects can be prevented by Vitamin E.
There are single strand breaks in DNA
Depolymerization of proteoglycans in connective tissue
Peroxidation of membrane lipid

Question 14

Source of precursors for other biosynthetic pathways.

Answer 14

succinyl COA --> heme synthesis
oxaloacetate --> glucose synthesis
citrate --> fatty acid synthesis
alpha ketoacids --> nonessential aminoa acid synthesis
malate --> gluconeogenesis

Question 15

What is the overall reaction for the citric acid cycle?

Answer 15

acetyl CoA + 3NAD+ + FAD –> GDP + Pi + 2H2O –> 2CO2 + 3NADH + FADH2 + GTP + 2h+ + CoASH

Question 16

What is the role of vitamins, coenzymes in the TCA

Answer 16

niacin = NAD
thiamin (vit B1) = TPP = decarboxylation of alpha-keto acids
riboflavin = (Vit B2) = FAD, FMN
pantothenic acid = CoASH = activation of acyl groups
lipoic acid = lipoamide = carrier of electrons and acyl groups

Question 17

Describe respiratory control in the TCA cycle

Answer 17

oxygen is required for cycle to run because TCA is tightly couples to ETC. Therefore electron carriers cannot be regenerated without the presence of oxygen

the rate of the cycle is dependent on the supply of oxidized cofactors (NAD+ and FAD) which are dependent on availablity of O2 and ADP

Question 18

What are the anapleurotic reactions?

Answer 18

these reactions replenish TCA intermediates
pyruvate carboxylase reaction - the major reaction: pyruvate –> OAA
trasaminase reactions: pyruvate + aspartate –> alanine + OAA
pyruvate + glutamate –> alanine + alpha ketoglutarate
malic enzyme reaction: pyruvate –> malate

Question 19

describe the hypoglycemia (fatal, neonatal and alcoholic)

Answer 19

fasting - overnight fast –> gluconeogenesis
neonatal –> within first few hours neonates start carrying out gluconeogenesis
alcoholic –> consumption of a large amount of ethanol depletes pyruvate. oxidation of alcohol produces large amounts of NADH. The electrons transferred from pyruvate to lactate to restore and regenerate NAD+

Question 20

What tissues carry out gluconeogenesis?

Answer 20

liver and kidney

Question 21

Describe the cori cycle

Answer 21

it is an interorgan cycle that operates between the liver and either the rbc or anaerobic skeletal muscle

lactate made in skeletal muscle or RBC can be extracted by liver and used for gluconeogenesis
enzyme: LDH
no net glucose synthesis

Question 22

What are the gluconeogenic amino acids?

Answer 22

give rise to intermediates in glycolysis or TCA
all amino acids, except leucine and lysine
major glucogenic amino acids: alanine

Question 23

Describe the alanine cycle.

Answer 23

interorgan xycle that operates between liver and skeletal muscle. Skeletal muscle derived from glucose, acts as an acceptor for amino groups from many of the individual amino acids. Alanine carries the amino group from muscle to liver, where they can be incorporated into urea for excretion. When alanine is in the liver it is reconverted to pyruvate.
This cycle is important because free ammonia is extremely toxic and most detox occurs in liver where it is converted to urea

Question 24

where does the gluconeogenic pathway take place?

Answer 24

the first step where oxaloacetate is converted to oxaloacetate is done in the mitochondria, but the other steps occur in the cytosol.

Question 25

Where does the energy for gluconeogenesis come from?

Answer 25

fatty acid oxidation

Question 26

Describe the malate-oxaloacetate shuttle

Answer 26

oxaloacetat is impermeable to the inner mitochondrial membrane. so it is converted to malate to leave mitochondria.

Question 27

Describe the energy requirements of concerting OAA to PEP

Answer 27

atp used in pyruvate carboxylase reaction

gtp used in PEPCK reaction

Question 28

Describe the regulation of the glucogenic pathway

Answer 28

its repressed after carb feeding, induced in starvation, stress and diabetes

covalent modification is induced by glucagon and mediated by cAMP-dependent protein kinase

two enzymes are phosphorylated: pyruvate kinase and bifunctional enzyme

pyruvate kinase: activity decreased by phosphorylation: slows conversion of PEP to pyruvate, more PEP for gluconeogenesis

bifunctional enzyme: 2phosphatase is activated when phosphorylated, level of fructose 2,6 bisphosphate decreased, increasing FBPase 1 activity and decrease in PFK1