FORM & FUNCTION (GSD & Gluconeogenesis)

Question 1

glycogen storage disease (GSD)

Answer 1

-efficiencies in enzymes affecting either glycogen synthesis (glycogenesis) OR glycogen breakdown (glycogenolysis)
-caused by genetic defects
-frequency varies between animal and breed types

Question 2

common symptoms of GSD

Answer 2

-hypoglycemia (low blood glucose)
-hepatomegaly (liver enlargement)
-glucagon insensitive
-muscle weakness (can’t use glycogen as CHO storage)

Question 3

muscle GSD: type 7 (deficient in muscle-PFK)

Answer 3

-rare mutation in dogs (higher in spaniel breeds)
-glycolysis slows down at step 3
-impairs glucose conversion to ATP
-PFK activity in muscle is 1-4% (exercise intolerant)
-PFK activity in RBC is 6-22% (hemolytic crisis: death of RBC)

Question 4

hepatic GSD: type 1 (deficiencies in glucose-6-phosphatase)

Answer 4

-Von Gierke’s disease
-glucose always trapped via phosphorylation
-inability to regulate blood glucose in response to glucagon/E
-reported in Maltese puppies
-hepatomegaly, hypoglycemia (poor prognosis)
*most severe form (can’t use liver=major blood glucose regulator)

Question 5

hepatic GSD: Type III (deficiencies in 1,6-glucosidase)

Answer 5

-Cori’s disease
-incomplete glycogen breakdown (slow accumulation of branched glycogen)
-symptoms similar to type 1
->milder, muscle weakness at 2 months
>akitas and German Shepherds

Question 6

heaptic GSD: Type IV (deficiencies in glycogen branching enzyme)

Answer 6

-Anderson disease
-normally does 1,6 linkage (synthesis)
-forms long 1,4 linkage glycogen (low solubility)
=precipitate in liver (deposits)
-Norwegian forest cats & American quarter horses
-weakness at birth, eventually liver dysfunction

Question 7

Myopathic GSD: Type V (deficiencies in muscle glycogen phosphorylase)

Answer 7

-inability to breakdown 1-4 linkage
-exercise intolerant
>rhabdomyolysis (muscle fibers in blood stream)
>severe dehydration
>electrolyte imbalance
-resting muscle can use FATTY ACIDS
-exercise=induce symptoms
-reported in Charolais cattle and merino sheep

Question 8

hepatic GSD: Type VI (deficiencies in hepatic glycogen phophorylase)

Answer 8

-Hers disease
-only parital loss of function (reduced ability to breakdown 1,4 linkage)
-symptoms not as severe:
>moderte hypoglycemia
>ketosis
>growth retardation
>hepatomegaly (enlarged liver)

Question 9

demand for glucose

Answer 9

-constant (brain, RBC)
-glycogen supply is limited
>liver: half day supply for brain undering fasting conditions
-need a mechanism to maintain it between meals
*gluconeogenesis

Question 10

human adult brain glucose requirements

Answer 10

-120/160g per day

Question 11

gluconeogensis

Answer 11

-takes place in liver (primarily) and kidneys
-utilizes non CHO precursors
-reversal of glycolysis
-energetically expensive (6ATP)
*need to do it as brain and RBC need glucose energy
(brain can use ketones during starvation)

Question 12

substrates used for gluconeogenesis

Answer 12

-amino acids
-lactate
-glycerol
-propionate (ruminant)
*oxaloacetate (part of TCA cycle)

Question 13

phophophenol-pyruvate carboxykinase (PEPCK)

Answer 13

-converts oxaloacetate to phosphophenol pyruvate
*first committed reaction of gluconeogenesis
-regulated at mRNA level

Question 14

PEPCK activator

Answer 14

1. Glucagon: pancrease
2. Glucocorticoid: adrenal cortex
3. Thyroid hormone: thyroid
   *more mRNA=more oxaloacetate

Question 15

PEPCK inhibitor

Answer 15

-insulin: pancreas
-less mRNA=less oxaloacetate

Question 16

amion acid substrates

Answer 16

-form proteins breaking down
-further processed into various intermediates that are fed into TCA cycle
*process is cruicail for starvation survival
-muscle degradation from proteins being degraded

Question 17

lactate substrate

Answer 17

-from exercise when glycolysis far exceeds capacity of aerobic TCA
-lactate form muscle can be transported to liver
-liver converts it to pyruvate and then to glucose (costs 6ATP)
-net -4ATP (NOT SUSTAINABLE)
->+2ATP from glycolysis, -6ATP from process in liver (2 pyruvate to 1 molecule of glucose)

Question 18

glycerol substrate

Answer 18

-by-product of fat breakdown (lipolysis)
1. Free glycerol recirculates to liver
2. Phophorylated by glycerol kinase
3. Glyceraldehyde-3-phosphate is an intermediate product of glycolysis/gluconeogenesis
*important source for gluconeogenesis during starvation