Carb Metabolism Test One

Question 1

Tauri

Answer 1

deficiency in PFK1 the rate limiting step of glycolysis. Characterized by hemolytic anemia, jaundice, exercise induced cramps and muscle weakness.

Question 2

Fanconi-Bickel Syndrome

Answer 2

autosomal recessive mutation in GLUT 2. Cannot take up glu, fru, gal. Characterized by failure to thrive, hepatomegaly, fasting hypoglycemia and postprandiol hyperglycemia. Supplement vitamin D and phosphate to treat.

Question 3

Fructose-1,6-Bisphosphate Deficiency

Answer 3

Disorder of Gluconeogenesis! It is the RLS, and has signs similar to Tauri disease of glycolysis. It presents in early child hood or infancy and is characterized by hypoglycemia, lactic acidosis, and ketosis. You cant generate glucose!

Question 4

Von Gierke disease

Answer 4

AKA GSD1. Deficiency in Glucose 6 Phosphatase. Can’t cleave G6P to glucose so G6P builds up leading to hepatomegaly, fasting hypoglycemia (bc glucose can’t be released) and lactic acid build up.

Question 5

Galactosemia

Answer 5

Commonly caused by inherited deficiency GALT. Infants FTT, also see cataracts (due to the build up of galactitol), hepatomegaly, jaundice, significant elevation of blood galactose levels.

Question 6

Galactokinase Deficiency

Answer 6

Non classical variant type two leads to accumulation of galactose and galactitol in blood and urine, cataracts are seen in early infancy.

Question 7

G6PD deficiency

Answer 7

The rate limiting enzyme in the pentose phosphate pathway! This enzyme reduces NADP+ to NADPH and oxidizes G6P . A deficiency presents with hemolytic anemia when NADPH need is elevated, such as in an infection or when taking certain medications. Affects those of African descent more.

Question 8

GSD 0

Answer 8

Deficiency in Glycogen Synthase. The RLE of glycogenesis. No synthesis or storage of glycogen occurs, so these patients rely on immediate sources of glucose for energy. Presents with hypoglycemia especially when sleeping and mm cramps often. Tx is to eat often.

Question 9

How to remember GSD 1-5 names:

Answer 9

(Pneumonic skips GSD 0) Volcano Pompe Caused A Massive Heartache

Question 10

GSD 2

Answer 10

Pompe disease, a deficiency in Acid Maltase/a-glucosidase which imparis lysosomal glycogenolysis. Glycogen accumulates in the lysosome and usually patients die of heart failure in infancy. Tx with recombinant a-glucosidase!!

Question 11

GSD 3

Answer 11

Cori disease, a deficiency in a-1,6-glucosidase (de branching enzyme) results in large numbers of short branches of glycogen. Light hypoglycemia and hepatomegaly.

Question 12

GSD 4

Answer 12

Anderson disease, a deficiency in glucosyl 4:6 transferase (branching enzyme). This results in long chain glycogen with few branches. Causes enlargement of spleen and liver. Death occurs by five.

Question 13

GSD 5

Answer 13

McArdle disease, a deficiency in muscle glycogen phosphorylase (GP). The RLS of glycogenolysis! Cant supply muscle with enough glucose for energy results in weakness fatigue, cramps and myoglobiburia. Exercise intolerance!

Question 14

GSD 6

Answer 14

Hers disease, a deficiency in liver GP. Prevents breakdown of glycogen in the liver so it accumulates causing hepatomegaly. Also results in hypoglycemia.

Question 15

Describe the GLUT’s:

Answer 15

1. GLUT 1: RBC’s and brain, has a high affinity for glucose, low Km, unregulated
2. GLUT 2: Liver and pancreas beta cells, low affinity for glucose and high Km, unregulated
3. GLUT 3: Neurons, high affinity, un regulated
4. GLUT 4: Adipose and skeletal mm, heart, medium affinity medium Km, Insulin depedent**
   
   1. GLUT 4 held in vesicles and relased to membranes due to insulin signaling to take up more glucose.

Question 16

Regulators of PFK?

Answer 16

• Activated: AMP, body has low energy signaling more is needed, F26BP, insulin.
• Inhibitory: ATP, glucagon Citrate

Question 17

What steps of glycolysis utilize ATP and produce ATP?

Answer 17

Hexokinase utilizes ATP

PFK-1 (RLE) uses ATP

Phosphoglycerate Kinase produces ATP

Pyruvate Kinase produces ATP

(G3PDH produces NADH)

Question 18

What are the three checkpoints of glycolysis?

Answer 18

Hexokinase/glucokinase

PFK-1

PK

Activities influenced by ATP and AMP, Glucose, and Insulin and Glucagon

Question 19

What type of receptor does insulin bind to and what is the process? How does this impact PFK1 and PK?

Answer 19

• RTK

1. Insulin binds RTK which stimulates PP1 a phosphatase to remove phosphates either activating or de- activating moleucles.
2. In the case of PFK1 isulin activates PP1 to dephosphorylate (+ affect) PFK-2/FBPase-2 to make F-2,6-BP which activates PFK-1.
3. With PK insulin stimulates PP1 to dephosphorylate PK which makes it active. (glucagon would stimulate GPCR cAMP and then PKA which would phosphprylate PK inactivating it)

Question 20

How is G6P a junction point in metabolism?

Answer 20

G6P can go to the PPP, or get converted into G1P and go to Glycogenesis or galactose metabolism

Question 21

Disorders of glycolysis main symptoms and what enyzme defect is main cause?

Answer 21

Pyruvate Kinase is the major cause of most glycolysis disorders and Hemolytic anemia is a major sign.

• Clinical marker for hemolytic anemia is elevated levels of lactate dehydrogenase and unconjugated bilirubin.

Question 22

Describe Type one and Type two diabetes:

Answer 22

1. severe insulin deficiency due to loss of pancreatic beta cells usually due to immune system attacking.
2. Insulin resistance that can progress to the loss of Beta cell function.

Can be caused by mutations in GK and mitochondrial genes, defective insulin recveptor, pancreatitis cancer of pancreas or infection.

Question 23

What steps do Gluconeogenesis bypass in glycolysis and how? What is the purpose?

Answer 23

• Bypass PK with Pyruvate Carboxylase (needs Biotin cofactor ** also a mitochondrial enzyme!) and PEP carboxykinase (Uses GTP**)
• Bypass PFK-1 with Fructose-1,6-Bisphosphatase (RLE!!)
• Bypass Hexo/Gluco kinase with Glucose-6-Phosphatase

Purpose is to generate glucose NOT energy, this process uses ATP. Net use is 6, 4ATP and 2 GTP

• Glucagon Citrate, Cortisol, Thyroxine and Acetyl CoA are positive regulators
• ADP, AMP, Fru-2,6-BP are negative

Question 24

Describe regualtion of the RLE in Gluconeogenesis.

Answer 24

Postive: cortisol and citrate

Negative: AMP and Fru-2,6-BP

Enzyme is Fructose-1,6- Bisphosphatase which breaks F16BP to F6P

Question 25

What is sucrose and lactose, and what type of transporter takes up fru, glu, gal?

Answer 25

• Surcrose: Glu + Fru
• Lactose: Glu + Gal
• Gal/Glu= SGLT 1 (found in Small Intestine, Na absorption follows)
• Fru=GLUT 5

Question 26

How is glucose converted to fructose?

Answer 26

1. Glucose is reduced to sorbitol by aldolase reductasae.
2. Sorbitol is oxidized to fructose by sorbitol dehydrogenase
   
   1. Sorbitol dehydrogenase not in kidneys retina and schwann cells and can accumulate sorbitol resulting in retinopathy cataracts and peripheral neuropathy

Question 27

What is the significance of fructose metabolism and high fructose corn syrup?

Answer 27

Fructose metabolism occurs faster than glucose metabolism and bypasses rate limiting steps using fructokinase and triose kinase. Meaning there is no regualtion to its metabolism. DHAP and G3P from thiss are processed by glyocolysis to pyruvate and acetyl CoA. Excess Acetyl CoA is converted to TAG’s and this is why foods with HFCS can lead to obesity. Also fatty liver!

Question 28

Purpose of PPP, RLE and phases?

Answer 28

Produces Ribulose5P and NADPH necessary for reductions. Occurs in cytosol!

• Glucose6P Dehydrogenase is the RLS (oxidative stage) which reduces NADP+ to NADPH and oxidizes G6P to 6-phosphoglucono-delta-lactone
  
  • NADPH regenerates Glutathione (an antioxidant) that detoxifies H2O2.
• Oxidative phase produces 2 NADPH and 1 CO2 using G6PDH to make NADPH which makes glutathione (G-SH) using glutathione reductase. G6P is oxidized to 6-PGD-lactone to then form Ribulose 5P and generate more NADPH.
• Non Oxidative Phase is reversible, unlike the oxidative, and the end products shunt to glycolysis gluconeogenesis or nucleodtide synthesis paths depending upon the need.

Question 29

If the body has a high demand for Ribulose 5P what phase is favored? WHat about high demand for NADPH?

Answer 29

1. Oxidative phase favored to make R5P
2. Non Ox favored to shunt products into gluconeognesis for re entry into PPP

Lung liver high PPP and Phagocytic cells very high activity of PPP

Question 30

Name important enzymes in Glycogenesis and Glycogenolysis and regulations.

Answer 30

• Glycogen Synthase: RLE! catalyzes transfer of glucose from the UDP glucose to the non reducing end of the glycogen chain. a-1,4 glycosidic bonds are formed between the glucose molecules.
  
  • GS dephosphorylated is active, PKB phosphorylates PP1(+) GSK3 phosphorylated is inactive and PP1 DEPHOS GS. Insulin starts cascade.
• Glucosyl (4:6) Transferase: creates branches in the glucose chain via a-1,6 glycosidic linkages. Once the chain reaches 11 glucose residues 7 chains are broken off at 1,4 link and replaced by 1,6 link.
• Glycogen Phosphorylase: RLE! of glycogenolysis. cleaves glucose as G1P from the NON REDUCING end. PYRIDOXIAL PHOSPHATE is cofactor**. Cleavage continues until GP within 4 residues of branch point.
  
  • Phosphorylated Glycogen Phosphorylase is active! Glucagon binds GPCR (ac–>cAMP–>pKA). PKA phosphorylates Phosphorylase Kinase, which makes it active and phosphorylates GP.
• Debranching enzyme: transfer block of 3 out of the four remaining glucose monomers to the NON reducing forming a 1,4 bond
• Glucose-6-Phosphatase cleaves G6P to free glucose